2016 Student Projects - Sept - Final PDF

Student Research Projects in
Cardiovascular Disease, Diabetes &

Metabolism
2016
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Baker IDI Student Project 2016
Index of Projects by Laboratory

Aboriginal Health ....................................................................................................... 3
Cardiac Hypertrophy .................................................................................................. 5
Cellular & Molecular Metabolism............................................................................... 9
Diabetes & Dyslipidaemia ........................................................................................ 11
Diabetic Complications............................................................................................. 14
Heart Failure Research ............................................................................................. 22
Heart Failure Pharmacology ..................................................................................... 24
Lipoproteins & Atherosclerosis ................................................................................ 30
Metabolic & Vascular Physiology ............................................................................. 33
Neuropharmacology ................................................................................................ 35
Vascular Pharmacology ............................................................................................ 39
Muscle Biology & Therapeutics ................................................................................ 43

Project title: A comprehensive approach to Aboriginal and Torres Strait Islander Tobacco Control (CATS)
& Reducing smoking among adolescents
Laboratory: Aboriginal Health
Primary Supervisor (s) Sandra Eades, Catherine Chamberlain
Contact: Catherine.chamberlain@bakeridi.edu.au 8532 1207
Research Focus: Strategies to reduce smoking among Aboriginal and Torres Strait Islander peoples
Keywords tobacco, smoking, Aboriginal and Torres Strait islander, adolescents
Project description:
Tobacco smoking among Aboriginal and Torres Strait Islander people is the leading cause of health
inequities in this population, and its control is essential to “closing the gap” in health status between
Aboriginal and other Australians. Australia, however, currently lacks a comprehensive framework that
guides and monitors the effectiveness of tobacco control efforts among Aboriginal people at the local,
state and national levels. (Eades and Chamberlain 2015).
This project, auspiced under the Australian Prevention Partnership Centre, aims to establish parameters
for reducing smoking among Aboriginal and Torres Strait Islander peoples. A review of current framework
is being conducted to establish parameters for assessing evidence and current activities for tobacco
control in the medium to long term. There are a number of objectives which would be amenable to 1-2
student projects, including:
1. Conducting a an overview of reviews about ‘what works’ to reduce tobacco use among Aboriginal
and Torres Strait islander Australians and map against the framework using an ‘evidence gap
map’.
2. Assist with conducting an audit of current tobacco reduction programs across several jurisdictions
and map against the ‘evidence gap map’
3. Explore the determinants of smoking uptake among Adolescents (using data generated from
NHMRC-funded adolescent study in 3 jurisdictions).
4. Develop potential interventions focused on reducing smoking uptake among Aboriginal
adolescents.
Project related methods/skills/technologies:

• Systematic review skills, including use of evidence mapping software, within an evidence-based
framework
• Conducting a survey/interviews/audit of current tobacco reduction programs and using evidence
mapping software
• Data planning, collection and analysis of factors influencing adolescent smoking uptake (suitable
for PhD level)
• Developing research design and intervention development skills with a pilot intervention to
reduce smoking uptake.
Aboriginal and/or Torres Strait Islander students are warmly encouraged to consider this project.
Knowledge and/or experience working with Aboriginal and Torres Strait Islander communities is desirable.
References:
1. Eades S, Chamberlain C. Seeking a comprehensive approach to tobacco control for Aboriginal and
Torres Strait Islander people. The Medical Journal of Australia. 2015;202(10):511-512
2. Evidence gap maps http://www.3ieimpact.org/evaluation/evidence-gap-maps/ accessed 30/7/2015
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Project title:
'Generation Now': Exploring Health Trajectories in Aboriginal Adolescents and Youth
Laboratory: Aboriginal Health
Primary Supervisor (s)

Sandra Eades; Lina Gubhaju; Catherine Chamberlain
Contact:
Email: Lina.Gubhaju@bakeridi.edu.au Phone: 8532 1634
Research Focus: Health and wellbeing of Aboriginal adolescents

Keywords
Aboriginal health; Adolescent health; Longitudinal cohort studies; Participant recruitment
Despite the importance of transitions in adolescence to future health, there has been little attention given
to adolescent health in recent efforts to 'close the gap' in Aboriginal health and disadvantage. Aboriginal
Young people experience significantly poorer health and greater social and economic challenges to future
health than other young Australians. Whilst cross-sectional data provide a snapshot of the current health
and wellbeing of Aboriginal adolescents, there are major gaps in evidence and longitudinal studies
highlighting health trajectories and opportunities for appropriate interventions are urgently needed.
The aim of this project is to establish and conduct the first wave of follow-up for a cohort of approximately
2,250 Aboriginal young people aged 10 to 24 years recruited from remote, rural and urban Aboriginal
communities, in order to:
1. Quantify patterns of: physical and mental health risk and protective behaviours; and major physical and
mental health conditions and disability
2. Describe the social and environmental context in which these young people are growing up including
community, school, family and individual level factors;
3. Quantify changes in resilience and risk behaviours and health outcomes over time;
4. Identify factors relating to resilience and risk behaviours and physical and mental health outcomes at
baseline and changes over time;
5. Establish partnerships with communities to better understand factors relating to positive adolescent
and youth health and support them to take action to improve it.
Multiple research projects are expected to arise from this program of work. Studies will involve participant
recruitment, questionnaire development/pilot testing and collection of qualitative and quantitative data.
Students interested in this research area are encouraged to contact the supervisors listed above to
develop a research proposal.
Aboriginal and/or Torres Strait Islander students are warmly encouraged to consider this project.
Knowledge and/or experience working with Aboriginal and Torres Strait Islander communities is desirable.
• Epidemiology and biostatistics

• Participant recruitment for research studies
• Data collection and analyses
• Experience in Aboriginal health
4
Project title: Evaluating the off-label use of tilorone as a novel therapeutic for heart failure
Laboratory: Cardiac Hypertrophy
Primary Supervisor (s) Dr Bianca Bernardo and A/Prof Julie McMullen
Contact:
bianca.bernardo@bakeridi.edu.au 8532 1167
Research Focus:
Developing new therapies for the treatment of heart failure
Keywords: heart failure, fibrosis, tilorone, novel therapies
Synopsis: Heart failure is one of the leading clinical problems in Australia, and its significance is increasing
as the population ages. Existing therapies typically slow, rather than prevent or reverse heart failure
progression and often have undesirable side effects. Thus, innovative and efficacious therapies that can
prevent heart failure are urgently needed. Scarring (also called fibrosis) of the heart is a key clinical
correlate of declining heart function. Recently, tilorone, an FDA approved drug which is primarily
prescribed for viral infections and diarrhoea was shown to inhibit scarring in a mouse model of lung
disease. We have since generated exciting Preliminary Data that demonstrate that tilorone can regulate
the expression of a key anti-scarring pathway in heart cells called the bone morphogenetic protein
pathway, and that administration of tilrone in a mouse model of heart failure can attenuate cardiac
fibrosis.
Hypothesis: Tilorone may therefore act as a potential novel therapeutic to inhibit scarring and preserve
heart function in a setting of heart failure.
Aim: To determine the effect of tilorone on fibrosis and cardiac function in a mouse model of pathological
cardiomyopathy with established adverse cardiac remodelling, fibrosis and dysfunction.
• Experimental mouse procedures (echocardiography, dissection, i.p. injections)

• qPCR
• Western blotting
References:
1. Lepperantra et al., 2013 Am J Respir Cell Mol Biol 48:448-55

2. Massague et al., 2005 Genes Dev 19: 2783-2810
3. Bernardo, B.C., Ooi, J.Y.Y. and McMullen, J.R. (2012) The Yin and Yang of Adaptive and Maladaptive Processes in
Heart Failure. Drug Discovery Today: Therapeutic Strategies. 9(4): e163-e172.
4. Tham, Y. K., B. C. Bernardo, J. Y. Ooi, K. L. Weeks and J. R. McMullen (2015). "Pathophysiology of cardiac hypertrophy
and heart failure: signaling pathways and novel therapeutic targets." Arch Toxicol. Feb 24. [Epub ahead of print]
5. Zeisberg et al., 2003 Nat Med 9:964-8
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Project title: Atrial fibrillation and phosphoinositide 3-kinase signalling in the heart
Primary Supervisor (s) A/Prof Julie McMullen
Contact:
Julie.mcmullen@bakeridi.edu.au 8532 1194
Research Focus:
Understanding mechanisms by which a decrease in PI3K makes the heart susceptible to AF
Keywords: heart, cardiac function & rhythm, PI3K signalling
Synopsis: Atrial fibrillation (AF) is a cardiac disorder. It is the most common type of arrhythmia causing an
irregular heart beat, weakness, fatigue and dizziness. AF is associated with increased risk of mortality,
stroke and heart failure. Our laboratory has had a long term interest in the role of phosphoinositide 3-
kinase (PI3K) in the heart. Utilising genetic mouse models, we have shown that increasing PI3K-Akt
signalling in the heart provides protection against cardiac pathology, whereas decreasing PI3K can lead to
cardiac dysfunction, heart failure, and increase the susceptibility to AF.
Aim: To understand how and why a reduction in PI3K increases the susceptibility to atrial fibrillation.
• Experimental mouse procedures (echocardiography, ecg, dissection)

• qPCR
• Histological analyses
References:
1. Pretorius L, Du XJ, Woodcock EA, Kiriazis H, Lin RC, Marasco S, et al. Reduced phosphoinositide 3-kinase
(p110alpha) activation increases the susceptibility to atrial fibrillation. Am J Pathol. 2009;175(3):998-1009.
3. Sapra G, Tham YK, Cemerlang N, Matsumoto A, Kiriazis H, Bernardo BC, Henstridge DC, Ooi JYY, Pretorius L, Boey
EJH, Lim L, Sadoshima J, Meikle PJ, Mellet NA, Woodcock EA, Marasco S, Ueyama T, Du XJ, Febbraio MA, McMullen
JR. The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice. Nature Communications
5:5705 doi: 10.1038/ncomms6705, 2014.
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Project title: Understanding and overcoming cardiotoxicity associated with new cancer therapies
Primary Supervisor (s) A/Prof Julie McMullen and Dr Jenny Ooi
Contact:
Julie.mcmullen@bakeridi.edu.au 8532 1194
Research Focus:
Understanding cardiotoxicity of anti-cancer agents and identifying safer alternatives.
Keywords: heart, cardiac function & rhythm, anti-cancer agents
Synopsis: Cancer therapeutics have evolved dramatically in the last five years with an explosion of potent
small molecule inhibitors that target key survival pathways in the cancer cell. Many of these pathways are
also crucial for cardioprotection. Hence, although the use of targeted agents in the clinic may ameliorate
“traditional” side-effects such as myelosuppression and infections, they may paradoxically increase the
risk of serious cardiac events. A thorough understanding of how these agents impact cardiac signalling is
critical for their safe and widespread use in the community. Our laboratory has had a long term interest in
the role of phosphoinositide 3-kinase (PI3K) in the heart. Utilising genetic mouse models, we have shown
that increasing PI3K-Akt signalling in the heart provides protection against cardiac pathology, whereas
decreasing PI3K can lead to cardiac dysfunction, heart failure, and increase the susceptibility to atrial
fibrillation (AF). Despite the beneficial effect of PI3K in the heart, PI3K is amplified and mutated in a wide
range of cancers. Thus, inhibiting components of the PI3K pathway is currently one of the most active drug
developments in the cancer field.
Aim: To study the impact of anti-cancer agents on PI3K-Akt signalling in the heart and assess cardiac
function.
• Experimental mouse procedures (echocardiography, dissection, i.p. injections)

• qPCR
• Cell culture
References:
1. Pretorius L, Du XJ, Woodcock EA, Kiriazis H, Lin RC, Marasco S, et al. Reduced phosphoinositide 3-kinase
(p110alpha) activation increases the susceptibility to atrial fibrillation. Am J Pathol. 2009;175(3):998-1009.
3. McMullen JR, Boey EJ, Ooi JY, Seymour JF, Keating MJ, Tam CS. Ibrutinib increases the risk of atrial fibrillation,
potentially through inhibition of cardiac PI3K-Akt signaling. Blood. 2014;124(25):3829-30.
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Project title: Identification of PI3K-regulated noncoding RNAs in cardiac diseases
Primary Supervisor (s) Dr Jenny Ooi, A/Prof Julie McMullen
Contact: Julie.mcmullen@bakeridi.edu.au, 85321194

jenny.ooi@bakeridi.edu.au, 85321712
Research Focus: Bioinformatics approaches for cardiac disease
Keywords Cardiac hypertrophy, bioinformatics, microRNAs, noncoding RNAs
Heart failure is a major clinical problem affecting 1-3% Australians, therefore strategies to protect the heart
against insults that lead to heart failure such as pathological cardiac hypertrophy (growth of the heart) is
becoming more critical. Protein-coding genes are the most well studied sequences but only account for
approximately <2% of the genome. Previously unknown non-coding RNA species (ncRNA, formerly known as
‘junk’) have been discovered, and add a new dimension and complexity to the regulation of DNA, RNA and
protein. MicroRNAs (miRs) are a family of small RNAs that play important roles in the regulation of target
genes. Our laboratory has successfully regulated one of these miRNAs with an RNA-based therapy in a mouse
model with cardiac dysfunction, and demonstrated improved outcome and reduced pathology with this
treatment strategy (1, 2).
Previously, we demonstrated that the gene phosphoinositide 3-kinase (PI3K) protects the heart in settings of
cardiac stress (3). We identified miRNAs controlled by PI3K and reported that regulation of these PI3K-
controlled miRNAs was beneficial in models of heart failure (3). The main aim of this project is to identify other
non coding RNAs controlled by PI3K. We have collected tissues from these mice and with the development and
improvement of deep sequencing technologies we now have the opportunity to identify and comprehensively
assess the role of other small ncRNAs in addition to miRNAs simultaneously (3).
This project will use bioinformatics approaches to investigate changes in other small RNAs and build ncRNA-
associated networks that will improve our understanding of the pathways that regulate complex diseases like
heart failure. After identification of key miRNAs/ncRNAs, the student will use molecular and cell culture
experimental techniques to perform validations.
• Bioinformatics
• Molecular techniques
References:
1. Bernardo BC, Gao XM, Tham YK, et al. Silencing of miR-34a Attenuates Cardiac Dysfunction in a Setting of
Moderate, but Not Severe, Hypertrophic Cardiomyopathy. PLoS One 2014; 9:e90337.
2. Bernardo BC, Gao XM, Winbanks CE, et al. Therapeutic inhibition of the miR-34 family attenuates pathological
cardiac remodeling and improves heart function. Proc Natl Acad Sci U S A 2012; 109:17615-20.
3. Lin RC, Weeks KL, Gao XM, et al. PI3K(p110 alpha) protects against myocardial infarction-induced heart failure:
identification of PI3K-regulated miRNA and mRNA. Arterioscler Thromb Vasc Biol 2010; 30:724-32.
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Project title: Protective effects of exercise on metabolism
Laboratory: Cellular and Molecular Metabolism Laboratory
Primary Supervisor (s) Darren Henstridge, Mark Febbraio
Contact: darren.henstridge@bakeridi.edu.au 8532 1708

Research Focus:
My research focus is on how metabolism is impacted in different disease settings such as obesity, insulin
resistance, type 2 diabetes and Alzheimer’s disease. I have a special interest in the impact of exercise on
metabolism and the role of a family of proteins known as heat shock proteins (HSPs) on metabolic
function.
Keywords: Metabolism / exercise / mitochondria / Alzheimer’s disease / obesity / diabetes / liver /
skeletal muscle / heat shock proteins
Exercise is an effective therapy for many conditions where metabolism is impaired including obesity,
insulin resistance and type 2 diabetes. However, many people especially those who are frail or elderly
cannot exercise and of those that can exercise, rates of compliance are low. Therefore, finding
therapeutics that target pathways regulated by exercise and/or finding the best modes of exercise training
to give maximal metabolic effect are of interest. While many of the benefits of exercise in relation to
metabolic disease such as increased energy expenditure leading to weight loss and improved
cardiovascular function are well known, others such as exercise's affect on the type of bacteria in the gut
(gut microbiota) and the way in which exercise is protective against liver disease have been less studied.
We have ongoing research in our laboratory which is examining how exercise impacts the composition of
the bacteria in the gut and whether this alteration leads to any changes in metabolism. We are also
interested in how exercise improves fatty liver a condition that is associated with obesity and type 2
diabetes and a condition that can be a precursor to the development of liver cancer (hepatocellular
carcinoma).
Other interests of the laboratory include the identification of the role of the gene ACAD10 in whole-body
metabolic function. And the role of overexpression of heat shock protein 72 in the brain’s of mice with
Alzheimer’s disease.

• Animal (mouse) work on metabolism measuring fat mass (echoMRI), exercise training mice,
glucose tolerance etc.
• Laboratory analysis of tissue samples (protein levels, mRNA etc.)
• Data analysis and graphical presentation
References:
1. Jordy AB, Kraakman MJ, et al. Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-
fat diet-induced hepatosteatosis in mice. American Journal of Physiology, Endocrinology and Metabolism 2015;
308:E778-E791.
2. Berglund ED et al Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver. Diabetes. 2011.
60(11): 2720-9.
3. Evans CC, LePard KJ, et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-
induced obesity. PLOS ONE 2014; 9:1-14.
4. Turnbaugh PJ, Ley RE, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature
2006; 444:1027-1031.
5. Henstridge DC, Bruce CR, Drew BG, Tory K, Kolonics A, Chung J, Watson N, Estevez E, Gardner T, Lee-Young R,; Conner T,
Watt M, Carpenter K, Hargreaves M, McGee S, Hevener A, Febbraio, MA (2014). Activating HSP72 in rodent skeletal
muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance. Diabetes. 63(6):1881-
94.
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Project title: Does skeletal muscle mitochondrial dysfunction cause insulin resistance?
Laboratory: Cellular and Molecular Metabolism Laboratory / Diabetes & Dyslipidaemia

Primary Supervisor (s) Darren Henstridge (CMML), Brian Drew (Diabetes & Dyslipidaemia)
Contact: darren.henstridge@bakeridi.edu.au 8532 1708

brian.drew@bakeridi.edu.au 8532 1134
Research Focus:
This research focuses on whether insulin resistance (a state whereby the body no longer responds
normally to the actions of the hormone insulin) can be caused by skeletal muscle mitochondrial
dysfunction.
Keywords: Metabolism / mitochondria / obesity / diabetes / skeletal muscle / Parkin / PolG /insulin
resistance
Mitochondria are cellular organelles known as the "power plant” of the cell, due to their ability to convert
fatty acids and glucose to energy. In recent years, it has become clear that mitochondrial dysfunction and
defects in oxidative metabolism are characteristic features of many chronic illnesses including obesity,
insulin resistance, type 2 diabetes and neurodegenerative diseases. However, the underlying reasons for
this association are still poorly understood.
Mitochondrial activity is heavily contingent on the quality of mitochondria in the cell, which in turn is
governed by a balance between the generation of new mitochondria (mitochondrial biogenesis), the
removal of old or damaged mitochondria (mitophagy) and cellular processes including mitochondrial
fission (separation and isolation) and fusion (joining together). Fusion helps mitigate cellular stress by
sharing critical nutrients amongst mitochondria, whilst fission is a necessary pathway for the removal of
damaged mitochondria via mitophagy. Mitochondrial dysfunction has been shown to be induced by
various insults including, amongst others, mutation(s) in the mtDNA.
Over the years there have been various lines of evidence suggesting that mitochondrial dysfunction may
cause skeletal muscle insulin resistance. To definitively determine whether this is indeed the case, we are
creating two mouse lines that will have two genes involved in mitochondrial function (parkin and PolG)
deleted specifically from the skeletal muscle. To establish this resource we are using a technique called
CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindronic Repeast system) in collaboration with the
Australian Phenomics Network (APN). CRISPR is a novel gene editing tool that takes advantage of an
adaptive immune defense system used by Archea and bacteria, which facilitates genomic engineering in
mammalian organisms. Together, this will allow us to determine whether skeletal muscle specifc
mitochondrial dysfunction causse insulin resistance?

• Animal (mouse) work on metabolism measuring things such as body weight, fat and lean mass
(echoMRI), glucose tolerance etc..
• Laboratory analysis of tissue samples (protein levels, mRNA, mitochondrial function etc.)
• Data analysis and graphical presentation
References:
1. Drew BG, Ribas V, Le JA, Henstridge DC, Phun J, Zhou Z, Soleymani T, Daraei P, Sitz D, Vergnes L, Wanagat J, Reue K, Febbraio MA,
Hevener AL (2014). HSP72 is a Mitochondrial Stress Sensor Critical for Parkin Action, Oxidative Metabolism, and Insulin Sensitivity in
Skeletal Muscle. Diabetes, 63(5):1488-505.
2. Henstridge DC, Bruce CR, Drew BG, Tory K, Kolonics A, Chung J, Watson N, Estevez E, Gardner T, Lee-Young R,; Conner T, Watt M,
Carpenter K, Hargreaves M, McGee S, Hevener A, Febbraio, MA (2014). Activating HSP72 in rodent skeletal muscle increases
mitochondrial number and oxidative capacity and decreases insulin resistance. Diabetes. 63(6):1881-94.
3. Safdar et al. (2011). Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator
mice. 108 (10), 4135-4140.
4. Sander et al. (2013). CRISPR-Cas systems for editing, regulating, and targeting genomes. Nature Biotechnology. 32, 347-355.
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Project title:
IDOL Regulation of Lipid Metabolism
Laboratory:
Diabetes & Dyslipidaemia
Primary Supervisor (s):
Dr Anna Calkin, Dr Brian Drew
Contact:
anna.calkin@bakeridi.edu.au 8532 1140
Research Focus:
Animal studies to investigate the role of IDOL in the prevention of cardiovascular disease, diabetes and
liver disease
Keywords
cholesterol, triglyceride, insulin resistance, diabetes, steatosis, myocardial infarction, mice
More than one in five Australians has elevated levels of circulating triglycerides caused by excess dietary
intake, genetics or diabetes. These excess triglycerides can accumulate in peripheral tissues where they
can have pathological effects. In the heart this result in increased risk of cardiovascular disease (CVD); in
skeletal muscle it can lead to insulin resistance and in the liver this can result in steatosis. Currently, there
are few effective therapies for lowering triglyceride levels. Thus, there is a need to prevent the damage
caused by excess triglycerides.
IDOL is an E3 ligase identified for its ability to degrade the LDL receptor (1). In addition, we have confirmed
its importance in regulating the accumulation of triglycerides in the heart and skeletal muscle. We have
various projects which will test the role of IDOL in protecting against the following,
- lipid-induced cardiac dysfunction
- lipid-mediated insulin resistance in skeletal muscle
- lipid-induced hepatic steatosis
These studies will involve the use of genetically modified mouse models as well as the use an adeno-
associated virus (AAV) to turn on the IDOL pathway in mice. These studies will involve the assessment of
metabolic parameters such as glucose tolerance, insulin sensitivity and the response to a myocardial
infarction. Tissues will be assessed for metabolic signaling and substrate metabolism using a range of
techniques including western blotting and qPCR as well as an Oroboros. Immunohistochemical,
histological and lipidomic approaches will also be utilised.
• Western blotting – assessment of metabolic signaling pathways

• Quantitative PCR – assessment of regulators of lipid metabolism
• Immunohistochemistry/Histology – tissue morphology/protein expression
• Lipidomics – assessment of lipid species
• Oroboros – analysis of cellular respiration
• Animal studies – AAV transduction, cross-breeding, metabolic assessment
References:
1. Zelcer et al, Transgenic expression of dominant-active IDOL in liver causes diet-induced

hypercholesterolemia and atherosclerosis in mice. Science 2009; 325(5936):100-104
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Project title: Characterizing new genetic approaches to improve mitochondrial health and prevent disease
Laboratory: Diabetes & Dyslipidaemia Laboratory (DDL)
Primary Supervisor (s) Brian Drew, Anna Calkin
Contact: Brian.drew@bakeridi.edu.au, Ph: 8532 1134

Anna.calkin@bakeridi.edu.au, Ph: 8532 1140
Research Focus: This project focuses on increasing energy production in cells by improving the health of
mitochondria in specific tissues including skeletal muscle, adipose and brain. We will test if this approach
may have benefit in treating diseases including diabetes, obesity and neurodegeneration.
Keywords: energy metabolism, mitochondria, obesity, diabetes, neurodegeneration
Numerous diseases including some cancers, diabetes, obesity and neurodegeneration are associated with
a decline in the health and function of mitochondria – small structures within every mammalian cell
responsible for generating energy. However, the cause of this mitochondrial dysfunction - or ways in
which we can prevent or reverse it remain incompletely understood.
In a healthy cell, mitochondria are continuously degraded and regenerated in a tightly controlled cycle
that results in a constant supply of fresh and efficient mitochondria. It is disruption of this tight cycle that
leads to mitochondrial dysfunction. Very little is known about the cellular mechanisms that control this
cycle, even though identification of these mechanisms could have significant therapeutic implications.
To this end, we have recently made some new and exciting findings that identify a number of important
proteins which regulate mitochondrial flux, and also appear to be critical to maintaining mitochondrial
health. Consequently, we have projects available that will test whether manipulation of these proteins in
various tissues (skeletal muscle, adipose tissue, brain) can effect mitochondrial dysfunction in cells and
mice, and therefore affect disease pathogenesis.
• Cell culture
• qPCR/Western blotting
• Genetic manipulation
• Mouse handling, phenotyping and characterization
References:
1. Riera CE at al., Nat Cell Biol, 2015
12
Project title:
Identification of Novel Regulators of Cholesterol Metabolism
Laboratory:
Diabetes & Dyslipidaemia
Primary Supervisor (s):
Dr Anna Calkin, Dr Eser Zerenturk, Dr Brian Drew
Contact:
anna.calkin@bakeridi.edu.au 8532 1140
Research Focus:
Cell culture and animal studies to validate novel regulators of cholesterol metabolism identified through
our proteomic/lipidomic discovery platform
Keywords
Cholesterol, Atherosclerosis, Mice, Gene Discovery, Novel Therapies
One in three Australians has elevated levels of circulating cholesterol caused by excess dietary intake,
genetics or diabetes. This can have pathological effects in peripheral tissues such as the heart, increasing
the risk of cardiovascular disease (CVD). Currently, although statins have had a substantial impact on
reducing plasma cholesterol and CVD risk, some individuals experience side effects such as muscle
soreness and others respond poorly, highlighting an unmet need for new cholesterol lowering therapies.
Thus, studies are required to identify novel regulators of cholesterol metabolism as potential targets for
therapeutic intervention.
We provide a novel approach to identify new pathway(s) associated with cholesterol regulation. We have
linked genetic differences in 100 strains of mice to changes in plasma cholesterol levels. Excitingly, this
approach has identified many new targets, never before linked to cholesterol metabolism.
This project will involve validation of these identified targets in liver cells and translation of these findings
to mouse models including a hypercholesterolaemic model developed by our group, L-sIDOL transgenic
mice (1). In vitro studies will be performed in the human liver cell lines, HepG2 and Hep3B, overexpressing
and inhibiting a given target and assessing outputs of cholesterol regulation such as induction of the LXR
and SREBP2 pathways. Animal studies will involve administration of target AAVs and assessment of
parameters including plasma and liver cholesterol levels, atherosclerotic lesion development and
cholesterol signaling pathways.
• Molecular biology – cloning, generation of adenovirus, expression constructs

• Cell culture – liver cell lines, primary liver cells, transfection, infection
• Assessment of cholesterol pathways - cholesterol uptake, western blotting, qPCR
• Animal studies – AAV transduction, metabolic assessment
References:
1. Calkin et al, Transgenic expression of dominant-active IDOL in liver causes diet-induced

hypercholesterolemia and atherosclerosis in mice. Circulation Research. 2014; 115(4):442-9
13
Project title: The role of Nox5 in diabetes associated cardiovascular disease
Laboratory: Diabetic Complications
Primary Supervisor (s) Dr. Stephen Gray and Prof. Karin Jandeleit-Dahm
Contact:
Stephen.gray@bakeridi.edu.au 8532 1198
Research Focus:
Oxidative Stress, Diabetic Complications, Vascular Disease
Keywords
The development of diabetic complications including vascular and renal disease is enhanced in diabetic
patients. However, the underlying mechanism as to why this disease process is accelerated is largely
unknown.
Oxidative has been proposed to play a key role in the development of diabetic complications, particular the
NADPH oxidase (Nox) family. There are primarily 4 Nox isoforms that have been shown to be important in
the development of diabetic complications, Nox1, 2, 4 and 5. All of these isoforms have increased
expression and activity in diabetic patients. Our group has established a role for the Nox1 isoform in the
development of diabetic atherosclerosis, and the Nox4 isoform in diabetic kidney disease. However, to date
a role for the Nox5 isoform in diabetic complications is unknown.
We have multiple Honors and PhD projects involving the role of Nox5 in diabetes associated
cardiovascular disease, which will focus on the following areas;
1- Vascular Reactivity
2- Atherosclerosis development and remodeling
3- Cardiovascular function
The projects will utilize a highly novel humanised Nox5 knockin mouse, where Nox5 is expressed only in the
vascular smooth muscle cells or the endothelial cells. The project will involve applying various experimental
techniques that include immunhistochemistry, RT-PCR for gene expression analysis and cell culture analysis
to delineate the role that Nox5 plays in the development of diabetic complications.

• Cell Culture
• RT-PCR
• Tissue morphology & histology
References:
1. Gray SP., et al. Nox1 plays a key role in diabetes associated atherosclerosis Circulation. 2013
2. Gray, S.P. and K. Jandeleit-Dahm, The pathobiology of diabetic vascular complications-cardiovascular and kidney
disease. J Mol Med (Berl), 2014.
3. Guzik TJ., et al. Calcium-dependent nox5 nicotinamide adenine dinucleotide phosphate oxidase contributes to
vascular oxidative stress in human coronary artery disease. J Am Coll Cardiol. 2008
4. Montezano AC., et al. Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (nox5) regulation by
angiotensin ii and endothelin-1 is mediated via calcium/calmodulin-dependent, rac-1-independent pathways in
human endothelial cells. Circ Res. 2010.
5. Jha, J.C., et al., Genetic Targeting or Pharmacologic Inhibition of NADPH Oxidase Nox4 Provides Renoprotection in
Long-Term Diabetic Nephropathy. J Am Soc Nephrol, 2014.
14
Project title: The role of Linagliptin in diabetes associated kidney disease
Contact:
Research Focus:
Diabetic complications, kidney disease,
Keywords
Diabetic nephropathy is the leading cause of end stage renal disease in the Western World and is
associated with enhanced morbidity and mortality. Linagliptin has been demonstrated to have
potential as not only a glyceamic control agent, but also as a direct reno-protective agent in
diabetes. However, the direct effect of linagliptin in the development of diabetic kidney disease
has not yet been examined.
The current honors project aims to investigate the direct renoprotective effects of linagliptin in a
rat model of STZ induced diabetic nephropathy and in a mouse model of spontaneous insulin
deficiency, the Akita mouse which develops diabetic nephropathy.
The project will involve the utilization of diabetic mice and rats. The end points of the study will
involve kidney tissue analysis for kidney structure and disease, ELISA and immunohistochemistry
for analysis of kidney function as well as RT-PCR and Western Blot to determine the mechanism
involved in disease development and progression.

• RT-PCR
• Animal handling
References:
1. von Eynatten M, Gong Y, Emser A, Woerle HJ. Efficacy and safety of linagliptin in type 2 diabetes subjects at
high risk for renal and cardiovascular disease: a pooled analysis of six phase III clinical trials. Cardiovasc
Diabetol.12:60.
2. McGill JB, Sloan L, Newman J, Patel S, Sauce C, von Eynatten M, Woerle HJ. Long-term efficacy and safety of
linagliptin in patients with type 2 diabetes and severe renal impairment: a 1-year, randomized, double-blind,
placebo-controlled study. Diabetes Care.36(2):237-244.
3. Watson AM, Gray SP, Jiaze L, Soro-Paavonen A, Wong B, Cooper ME, Bierhaus A, Pickering R, Tikellis C,
Tsorotes D, Thomas MC, Jandeleit-Dahm KA. Alagebrium reduces glomerular fibrogenesis and inflammation
beyond preventing RAGE activation in diabetic apolipoprotein E knockout mice. Diabetes.61(8):2105-2113.
15
Project title: The interaction between the Renin Angiotensin System (RAS) and Nox derived ROS in
diabetes associated vascular and renal disease.
Contact:
Research Focus:
Oxidative Stress, Diabetic Complications, Vascular and Kidney Disease
Keywords
The development of diabetic complications including vascular and renal disease is enhanced in diabetic
patients. However, the underlying mechanism as to why this disease process is accelerated is largely
unknown.
A number of mechanisms interact with each other to enhance the development of diabetic complications.
However, the level of interaction is unexplored. One such interaction is oxidative stress and the rennin
angiotensin system (RAS). Studies have shown that blocking the RAS system prevents the accelerated
development of kidney and vascular disease. In addition, studies have shown that blocking Nox derived
ROS also reduces the development of kidney and vascular disease development in diabetes. However, no
study has explored how these two systems interact and if the combined inhibition enhances the attenuation
of diabetes associated vascular and kidney disease development.
Our group has established animal models that have Nox isoforms genetically deleted in addition to
pharmacological inhibition of the RAS system.
The project on offer will explore this interaction using tissue collected from these Nox deleted diabetic mice
that have been administered RAS inhibitors. Furthermore, a novel aspect of these studies will be the co-
administration of a Nox inhibitor and RAS blocker to identify if there are enhanced effects on diabetic
complications development when two pathways are blocked at the same time.

• Cell Culture
• RT-PCR
References:
1. Gray SP., et al. Nox1 plays a key role in diabetes associated atherosclerosis Circulation. 2013
2. Gray, S.P. and K. Jandeleit-Dahm, The pathobiology of diabetic vascular complications-cardiovascular and kidney
disease. J Mol Med (Berl), 2014.
3. Jha, J.C., et al., Genetic Targeting or Pharmacologic Inhibition of NADPH Oxidase Nox4 Provides Renoprotection in
Long-Term Diabetic Nephropathy. J Am Soc Nephrol, 2014.
4. Watson AM, Gray SP, Jiaze L, Soro-Paavonen A, Wong B, Cooper ME, Bierhaus A, Pickering R, Tikellis C, Tsorotes D,
Thomas MC, Jandeleit-Dahm KA. Alagebrium reduces glomerular fibrogenesis and inflammation beyond preventing
RAGE activation in diabetic apolipoprotein E knockout mice. Diabetes.61(8):2105-2113.
16
Project title: The role of let 7 micro-RNA in atherosclerosis: endothelial cells
Laboratory: Genes and Diabetes (Diabetic Complications Laboratory)
Primary Supervisor (s): Phillip Kantharidis
Contact: Phillip Kantharidis

Phillip.kantharidis@bakeridi.edu.au 8532 1462
Research Focus:
Diabetes associated atherosclerosis
Keywords
microRNA, atherosclerosis, endothelial cells, inflammation
Patients with diabetes have mortality from cardiovascular disease that is over twice that observed in the
general population, resulting in atherosclerotic plaque formation. The diabetic plaque is characterized by
macrophage accumulation and abnormalities in both aortic endothelial and vascular smooth muscle cell
function. Within the atherosclerotic cytokine network, tumor necrosis factor-alpha (TNF-alpha) is
implicated as a key molecular driver. Our data in vascular smooth muscle cells suggests that the let-7
micro-RNA family may have an important role in the pathogenesis of the diabetic plaque, with TNF-alpha
down regulating the expression of this miRNA family. Restoring the expression of let-7 miRNAs in vascular
smooth muscle cells can attenuate TNF-alpha-mediated signaling. However, the impact of restoring let-7
expression in aortic endothelial cells and macrophages is unclear. This project will investigate whether
restoring let-7 miRNA levels in primary mouse aortic endothelial cells and macrophages can suppress
inflammatory signals mediated by TNF-alpha. The project will involve the use of transfection techniques
but also the use of novel therapeutic compounds to attenuate the effect of TNF and hence
atherosclerosis.
• Animal experiments
• Tissue culture
• Transfection with miRNA mimics
• rtQ-PCR analysis for gene and microRNA expression
• Western analysis
• NFkB reporter gene assays
• Monocyte adhesion assays
• Animal tissue handling, processing and analysis
References:
1. Wang B, Jha JC, Hagiwara S, McClelland AD, Jandeleit-Dahm K, Thomas MC, Cooper ME, Kantharidis P:
Transforming growth factor-beta1-mediated renal fibrosis is dependent on the regulation of transforming growth
factor receptor 1 expression by let-7b. Kidney international 2014, 85:352-61.
2. McClelland AD, Kantharidis P: microRNA in the development of diabetic complications. Clinical science 2014,
126:95-110.
3. Hagiwara S, Kantharidis P, Cooper ME: MicroRNA as biomarkers and regulator of cardiovascular development and
disease. Current pharmaceutical design 2014, 20:2347-70.
17
Project title: RNA biomarkers predictive of patients at risk of developing diabetic nephropathy

Research Focus:
Biomarkers for diabetic nephropathy
Keywords
microRNA, biomarkers, RNA-seq, bioinformatics
Not all patients with diabetes are at risk of also developing complications such as end stage kidney disease
and diabetes associated atherosclerosis. Approximately 30 % of patients develop these debilitating
conditions. Despite the research to date we do not have any good means of identifying patients at risk of
developing complications. In terms of the kidney, diabetic nephropathy is the most common cause of
chronic kidney disease in people with diabetes. This condition is characterized by glomerular changes such
as glomerular basement thickening, mesangial expansion, renal hypertrophy and the accumulation of
extracellular matrix (ECM) proteins. These changes are largely driven by TGF-β which stimulates ECM
production in many cell types.
The aim of this project is to use RNA-seq techniques to identify RNA biomarkers in urine from control and
diabetic patients which not only are diagnostic of disease, but more importantly may be able to predict
disease development. Archival and fresh samples will be used to identify RNA (mRNA and miRNA)
biomarkers and these will be then be tested against a panel of samples from patients whose history is
known. Potential biomarkers will be further assessed in terms of relevance to disease using in vitro assays
and animal models of diabetic nephropathy.
• RNA isolation techniques

• RNA-seq and bioinformatics
• Tissue culture
• Transfection with miRs
• rtQ-PCR analysis
• western analysis
References:
1. Hagiwara S, Kantharidis P, Cooper ME: MicroRNA as biomarkers and regulator of cardiovascular development and
disease. Current pharmaceutical design 2014, 20:2347-70.
3. Wang B, Komers R, Carew R, Winbanks CE, Xu B, Herman-Edelstein M, Koh P, Thomas M, Jandeleit-Dahm K,
Gregorevic P, Cooper ME, Kantharidis P: Suppression of microRNA-29 expression by TGF-beta1 promotes collagen
expression and renal fibrosis. Journal of the American Society of Nephrology : JASN 2012, 23:252-65.
4. Wang B, Koh P, Winbanks C, Coughlan MT, McClelland A, Watson A, Jandeleit-Dahm K, Burns WC, Thomas MC,
Cooper ME, Kantharidis P: miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression.
Diabetes 2011, 60:280-7.
5. Wang B, Herman-Edelstein M, Koh P, Burns W, Jandeleit-Dahm K, Watson A, Saleem M, Goodall GJ, Twigg SM,
Cooper ME, Kantharidis P: E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of
the profibrotic effects of transforming growth factor-beta. Diabetes 2010, 59:1794-802.
18
Project title: Lipoxin A4 analogues as a treatment for diabetic nephropathy

Research Focus:
Biomarkers for diabetic nephropathy
Keywords
Inflammation, microRNA, diabetic nephropathy
Diabetic nephropathy (DN) is the most common cause of chronic kidney disease in people with diabetes.
The major characteristics of DN include glomerular basement thickening, mesangial expansion, renal
hypertrophy and the accumulation of extracellular matrix (ECM) proteins. TGF-β is the most potent
inducer of renal fibrosis because it stimulates ECM production in many cell types, but because it also
transformed cells to a profibrotic phenotype, inducing the expression of other fibrogenic molecules (eg.
CTGF), thus amplifying the effect of TGF-β. Many fibrogenic mechanisms appear to converge on TGF-β and
its receptors to signal through the SMADs, MAPKs and other pathways. The role of altered expression of
certain miRNAs in TGFβ treated proximal tubular cells appears to contribute to the increased expression
of ECM proteins (collagens, fibronectin, αSMA, etc). Restoring the expression of some of these miRs can
attenuate the effects of TGFβ in terms of ECM synthesis.
However, the direct targeting of TGF-β as an anti-fibrotic treatment has been problematic because of the
critical role this factor plays in immune surveillance. We have found that a family of naturally occurring
molecules in the body (lipoxins) have the ability to modulate TGFβ signaling and restore the expression of
certain miRNAs that contribute to renal disease, and hence are able to reduce the damage caused by
diabetes in the kidney. Access to newly designed stable analogues of these compounds provides us with a
unique opportunity to test new treatments against diabetic nephropathy.
• rtQ-PCR (gene expression) analyses
• Tissue culture
• western analyses
• mitochondrial and oxidative stress assays
References:
Diabetes 2011, 60:280-7.
19
Project title: MicroRNAs and mitochondrial function in diabetic nephropathy

Research Focus:
The impact of altered miRNA expression on mitochondria
Keywords
Oxidative stress, mitochondria, microRNA, diabetes, kidney
Diabetic nephropathy (DN) is the most common cause of chronic kidney disease in people with diabetes. It
is characterized by scarring of the kidney, with changes in both glomeruli and the tubulointerstitial areas
of the kidney. The laying down of excess extracellular matrix (ECM) protein results in reduced kidney
function and finally leads to end stage renal disease. TGF-β is the most potent inducer of renal scarring,
stimulating ECM production in many cell types. More recently it has become evident that mitochondrial
structure and function is also affected by TGF-β1, contributing to the overall disease phenotype.
Our work has demonstrated that microRNAs play an important role to the regulation of ECM in the kidney
and more recently we have demonstrated the miR-21 in particular is important for mitochondrial biology
and targets several genes that are relevant to mitochondrial structure and function.
This project will investigate the link between elevated miR-21 in diabetic nephropathy and the effect this
has on mitochondria using renal proximal tubular cells as a model. Parallel studies will be conducted in
kidney tissue from diabetic animals to confirm findings and develop new strategies for the treatment of
diabetic nephropathy.
• rtQ-PCR (gene expression) analyses
• Tissue culture
• western analyses
• mitochondrial assays
• oxidative stress assays
References:
Diabetes 2011, 60:280-7.
20
Project title: Targeting the AT2R as a novel therapeutic approach for diabetes-associated atherosclerosis
Laboratory: Diabetes & Atherosclerosis
Primary Supervisor (s): A/Prof Terri Allen, Dr Bryna Chow
Contact: terri.allen@bakeridi.edu.au 8532 1453

bryna.chow@bakeridi.edu.au 8532 1311
Research Focus:
Diabetes is a major risk for the development of cardiovascular disease leading to the clinical consequences
of heart attacks, stroke and amputations and contributing to increased morbidity and mortality observed
in diabetes patients. Current treatment options fail to fully protect patients from macrovascular
complications of diabetes and thus new treatments are urgently needed. Our laboratory aims to address
key clinical questions centering on the prevention and treatment of diabetes-associated macrovascular
complications.
Keywords: Atherosclerosis, diabetes, cardiovascular disease, inflammation
Background: Atherosclerosis is well-implicated to be the main contributor to the mortality and morbidity
in diabetes patients (1). Hyperglycaemia often accelerates the progression and development of
atherosclerosis and cardiovascular disease. Following the rupture of an atherosclerotic lesion, diabetic
patients are at high risk of suffering from heart attacks and strokes. Angiotensin (Ang) II, the main effector
hormone of the renin-angiotensin system, is regarded as the key factor that drives the destabilisation of
atherosclerotic lesions on blood vessel walls. Its ability to stimulate the production and secretion
inflammatory, oxidative stress and fibrotic molecules during pathological conditions is well-considered to
be mediated primarily through its type 1 receptors (AT1Rs) subtype (2).
Interestingly, accumulating evidence has postulated that Ang II negatively regulates AT1R-mediated
actions and attenuates fibrosis by signalling through its type 2 receptors (AT2R). Although activation of the
AT2R has been shown to be protective in numerous diseased models (3-6), such an approach in type 1
diabetes has yet to be fully characterised.
Project aim: Therefore, the current project aims to specifically explore the role of the AT2R using the novel
selective non-peptide AT2R agonist, Compound 21 (C21) in a mouse model of atherosclerosis which
closely mimic the pathology of human plaque, and elucidate the signaling transduction pathways
associated with C21’s ability to regulate its activity. These studies are novel and crucial to an overall
program of research devoted to developing the clinical potential of C21 as a therapeutic intervention for
diabetic associated atherosclerosis. *Honours, Masters and PhD projects are available.

• Animal procedure
• Cell culture
• Protein biochemistry and molecular biology (i.e. Western blotting, ELISA)
• Gene analysis (i.e. Quantitative real time PCR)
• Histology
References:
1. Juutilainen A et al (2008) Similarity of the impact of type 1 and type 2 diabetes on cardiovascular mortality in middle-aged
subject. Diabetes Care 31, 714-719.
2. Ma TK et al (2010) Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. Br J Pharmacol
160, 1273-1292.
3. Johren J et al. (2004) Cardiovascular and renal function of angiotensin II type-2 receptors. Cardiovasc Res 62, 460-467.
4. Johansson, ME et al (2008) Angiotensin type 2 receptor is expressed in human atherosclerotic lesion. J Renin Angiotensin
Aldosterone Syst 9, 17-21.
5. Sales et al (2005) Angiotensin type 2 receptor is expressed in murine atherosclerotic lesions and modulates lesion evolution.
Circulation 112, 3328-3336.
6. Chang SY et al (2011) Angiotensin II type II receptor deficiency accelerates the development of nephropathy in type I diabetes
via oxidative stress and ACE2. Exp Diabetes Res 521076.
21
Project title: Dietary role in the prevention of heart failure – an intergenerational study
Laboratory: Heart Failure research Group
Primary Supervisor (s) Dr Francine Marques and Prof David Kaye
Contact: francine.marques@bakeridi.edu.au 8532 1916
Research Focus: epigenetic mechanisms to prevent f cardiac fibrosis
Keywords: heart failure, fibrosis, diet, epigenetics
Heart failure is the leading cause of death in developed countries. Patients with heart failure have marked
cardiac fibrosis, the scarring of the heart with the accumulation of fibroblasts and extracellular matrix,
leading to stiffness and, thus, a decrease in myocardial function. While the role of a high fat diet has been
well studied in the development of cardiovascular disease, the effect of a high fibre diet in the prevention
or attenuation of heart failure is less known. We have recently found that dietary manipulation in mice for
3 weeks prior to deoxycorticosterone acetate (DOCA) challenge (which causes hypertension and cardiac
fibrosis) has beneficial effects on cardiac structure. Recent studies performed in the context of other
inflammatory disease suggest that epigenetic modifications could also be passed on across generations.
The overall aim of this project will be to determine the effect of the maternal diet in the prevention of
myocardial fibrosis in the progeny. This will be achieved by treating pregnant mice with different diets,
DOCA surgery, in vivo echocardiography, immunohistochemistry to determine cardiac fibrosis, and
validation of DNA methylation and target messenger RNA (mRNA) sites in the progeny.

Mouse surgery, mouse echocardiography, immunohistochemistry (Masson’s trichrome), RNA and DNA
extraction, next-generation sequencing (bisulfite sequencing), real-time PCR.
22
Project title: Targets of microRNA miR-181a regulating blood pressure
Laboratory: Heart Failure research Group
Primary Supervisor (s) Dr Francine Marques, Prof Geoff Head, Prof Gavin Lambert
Contact: francine.marques@bakeridi.edu.au 8532 1916

Research Focus: mechanisms that regulate high blood pressure
Keywords: microRNAs, kidney, biomarker
High blood pressure (BP), also known as essential hypertension, is responsible for more than 50% of
cardiovascular deaths worldwide, being the principal risk factor for global burden of disease. Hypertension
is a multifactorial condition with a substantial contribution from heritable genetic factors. Unravelling the
molecular predisposition to high blood pressure (BP) has, however, proven challenging. MicroRNAs are
small non-coding RNAs which bind to untranslated regions of many genes including those responsible for
cardiovascular disease. We found previously that the microRNA miR-181a binds to and regulates the levels
of renin mRNA in cells in culture and is inversely associated with the level of expression of renin in the
kidney (Marques et al., Hypertension 2011; Jackson, Marques et al., Hypertension 2013). This microRNA
was also detected in the circulation and was associated with the BP level. Other genes besides renin seem,
however, to be involved (Marques et al., submitted). The aim of this project will be to determine if miR-
181a is associated with early markers of high BP and cardiovascular disease using 200 human plasma
samples obtained from young adults, and also whether miRNA levels change with exercise and/or diet. We
will also determine what other messenger RNAs are targeted by miR-181a, especially ones in pathways
that affect BP and cardiovascular disease. This will be achieved by performing bioinformatics analyses,
then validating the levels of these genes in tissues of models of hypertension (treated with a microRNA
mimic, renal denervation, etc), followed by cloning and in vitro transfection experiments.
This project will involve collaborations with the Menzies Institute for Medical Research, Tasmania.
Project related methods/skills/technologies: Bioinformatics, RNA extraction, real-time PCR, cloning and
microbiology, cell culture, transfections, luciferase assays, and statistical analyses
References:
1. Jackson KL, Marques FZ, Watson AM, Palma-Rigo K, Nguyen-Huu TP, Morris BJ, Charchar FJ,
Davern PJ, Head GA. A novel interaction between sympathetic overactivity and aberrant
regulation of renin by miR-181a in BPH/2J genetically hypertensive mice. Hypertension.
2013;64:775-81.
2. Marques FZ, Campain AE, Tomaszewski M, Zukowska-Szczechowska E, Yang YH, Charchar FJ,
Morris BJ. Gene expression profiling reveals renin mRNA overexpression in human hypertensive
kidneys and a role for microRNAs. Hypertension. 2011;58:1093-8.
3. Marques FZ, Romaine S, Denniff M, Eales J, Dormer J, Garrelds I, Nelson CP, Wojnar L, Musialik K,
Morris BJ, Samani NJ, Bogdanski P, Zukowska-Szczechowska E, Danser AHJ, Charchar FJ,
Tomaszewski T. Signatures of miR-181a on blood pressure and renal transcriptome. Submitted for
publication.
23
Project title: Circumventing Impaired Nitric Oxide Function in the Cardiovascular Complications of
Diabetes
Laboratory: Heart Failure Pharmacology
Primary Supervisor: Assoc Prof Rebecca Ritchie
Contact:rebecca.ritchie@bakeridi.edu.au 8532 1392
Research Focus:
Our laboratory seeks to improve the understanding of the causes of heart failure, identify new targets for
its precursors and develop new pharmacotherapies for delaying their progression.
Keywords: Cardiac function; Coronary vasculature; Diabetes; Nitric Oxide; Nitroxyl; Oxidative stress;
Platelets.
BACKGROUND: The global epidemic of diabetes mellitus is imposing an exponential burden on society –
not only because of the substantial associated healthcare costs, but also because of the poor health
outcomes for those with the condition, particularly as a result of diabetic cardiovascular complications-
induced morbidity and mortality. Impaired nitric oxide (NO) signalling is an independent marker of poor
prognosis. Defined as a diminution or absence of the protective cardiovascular actions downstream of NO,
the phenomenon is particularly manifest in diseased human vasculature, likely as a consequence of
elevated oxidative stress (see diagram). Loss of NO responsiveness is particularly debilitating in diabetes,
where cardiovascular emergencies (acute myocardial infarction, transient ischaemia, cardiogenic shock)
occur more frequently, yet the ability of NO-based pharmacotherapies to target platelet aggregation and
vasoconstriction is deficient. We have identified nitroxyl (HNO) as a putative strategy for enhancing NO
signalling in the heart and vasculature over the short- and longer-term, which we believe can potentially
address this clear area of clinical need.
GENERAL HYPOTHESIS: Diabetes-induced NO resistance in the heart and vasculature is exacerbated by
poor glycaemic control, and can be circumvented by HNO
AIMS: To determine whether diabetes induces NO resistance in the myocardium (not previously known),
to investigate the relationship between hyperglycaemia and NO responsiveness in the diabetic heart and
vasculature, and to demonstrate that HNO circumvents this impaired NO signalling induced by diabetes.
SIGNIFICANCE: Strategies that circumvent (for management of cardiovascular emergencies) and/or
ameliorate (targeting the incidence of these emergencies) impaired NO signalling in the diabetic heart and
vasculature will improve prognosis in affected patients, of substantial clinical importance.
24
• in vivo models of diabetic cardiac disease

• isolated rodent hearts ex vivo
• assessment of cardiac and vascular function
• biochemical techniques: Westerns, ROS detection, ELISA, real-time PCR, histology
References:
1. Huynh K, Bernardo BC, McMullen JR*, Ritchie RH*. Invited review: Diabetic cardiomyopathy: Mechanisms and
new treatment strategies targeting antioxidant signaling pathways. (2014). Pharmacol Ther 142: 375-415.
2. Chin KY*, Qin C*, Cao N, Kemp-Harper BK, Woodman OL, Ritchie RH. (2014). The concomitant coronary
vasodilator and positive inotropic actions of Angeli's salt in the intact rat heart are mediated by nitroxyl and
soluble guanylyl cyclase-dependent mechanisms. Br J Pharmacol 171: 1722–1734.
3. Irvine JC*, Cao N*, Gossain S, Alexander AE, Love JE, Qin C, Horowitz JD, Kemp-Harper BK, Ritchie RH. (2013).
HNO/cGMP-dependent antihypertrophic actions of isopropylamine-NONOate in neonatal rat cardiomyocytes:
potential therapeutic advantages of HNO over NO•. Am J Physiol 305: H365-H377.
4. Dautov R, Ngo DT, Licari G; Liu S; Sverdlov AL, Ritchie RH, Kemp-Harper BK, Horowitz JD, Chirkov YY. (2013). The
nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness. Nitric
Oxide 35: 72–78.
25
Project title: Annexin-A1 Mimetics: a Novel Therapeutic Approach for Targeting the Cardiac
Complications of Diabetes
Research Focus:
Keywords: Annexin-A1; Cardiac function; Diabetes; Heart failure; Inflammation.
BACKGROUND: Diabetes is Australia’s fastest growing chronic disease. The disease affects almost 2 million
Australians; diabetes increases heart failure risk 2.5-fold and accelerates its onset. Our laboratory has an
established track record for identifying new pharmacotherapies for diabetic cardiomyopathy. Building on
this experience, we have obtained recent evidence that cardiac inflammation is a key contributor to
myocardial damage in the diabetic heart. We have previously shown that the glucocorticoid-regulated
anti-inflammatory mediator annexin-A1 is a key regulator of cardiac viability and function. Annexin-A1
thus offers an attractive approach to minimise the detrimental consequences of diabetes on the heart.
GENERAL HYPOTHESIS: Annexin-A1-based therapies limit diabetic cardiomyopathy by reducing cardiac
inflammation and protecting cardiac contractile function.
AIMS: To compare the time-course of cardiac inflammation and impaired cardiac function, in both type 1
and type 2 diabetes, and to investigate annexin-A1 cardioprotection for the cardiac complications of the
disease in vivo
SIGNIFICANCE: The alarming global epidemic of diabetes gives rise to an ever-increasing heart failure
burden. We propose that annexin-A1 addresses the unmet clinical need of the extra burden posed by
concomitant diabetes, inflammation and cardiomyopathy. The potential cardioprotective annexin-A1
mechanisms represent a strategic new therapeutic intervention for diabetic cardiomyopathy. These
interventions may ultimately limit progression to heart failure and death in diabetes-affected patients.
26

• assessment of cardiac function
• biochemical techniques: Westerns, ELISA, real-time PCR, histology, immunofluorescence
References:
1. Qin C, Buxton KD, Pepe S, Cao AH, Venardos KM, Love JE, Kaye DM, Yang YH, Morand EF, Ritchie RH. (2013).
Reperfusion-induced myocardial dysfunction is prevented by endogenous annexin-A1 and its N-terminal
derived peptide Ac-ANX-A12-26. Br J Pharmacol 168: 238–252
2. Huynh K, Kiriazis H, Du XJ, Love JE, Gray SP, Jandeleit-Dahm KA, McMullen JR*, Ritchie RH*. (2013). Targeting
the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic
cardiomyopathy in mice. Free Rad Biol Med 60: 307-317.
4. Qin C, Yang YH*, May LM*, Gao XM, Stewart A, Tu Y Woodman OL, Ritchie RH. Invited review:
Cardioprotective potential of annexin-A1 mimetics in myocardial infarction. Pharmacol Ther (submitted
28/4/14).
27
Project title: Therapeutic targeting of the cardiac hexosamine biosynthesis - ROS axis to protect the
diabetic heart
Research Focus:
Keywords: Cardiac function; Diabetes; Glucose metabolism; Heart failure; Oxidative stress; Mitochondria.
BACKGROUND: Diabetes is Australia’s fastest growing chronic disease. The disease affects almost 2 million
Australians; diabetes increases heart failure risk 2.5-fold and accelerates its onset. Our laboratory has an
established track record for identifying new pharmacotherapies for diabetic cardiomyopathy, many of
which target reactive oxygen species (ROS). Building on this experience, we have obtained recent evidence
that the hexosamine biosynthesis pathway (HBP), an alternative fate of glucose, has now emerged as a
contributing factor to the cardiac complications of diabetes.
GENERAL HYPOTHESIS: that the concomitant impairments in both glucose handling and ROS that are
hallmarks of diabetes together provide an additional drive towards unchecked HBP dysregulation, such
that this post-translational modification switches from serving an adaptive, to a maladaptive, role,
affecting both cardiac function in vivo and mitochondrial integrity.
AIMS: The major goal of this study is to demonstrate that cardiac-directed therapeutic targeting of the
ROS-HBP axis will delay or even overcome diabetes-induced cardiac dysfunction in the intact heart in vivo.
SIGNIFICANCE: The lack of existing management of heart failure in the context of the poorer prognosis of
concomitant diabetes highlights a clear, unmet clinical need. By specifically regulating cardiac HBP
signalling in either the early or later stages of diabetes-induced heart failure, our approach is therapeutic
rather than prophylactic, in addition to permitting tissue-selective regulation of this important, otherwise
cytoprotective, post-translational modification.
28

• assessment of cardiac function
• assessment of mitochondrial function
• biochemical techniques: Westerns, ELISA, real-time PCR, histology, immunofluorescence
References:
1. Huynh K*, McMullen JR*, Julius TL, Tan J, Love JE, Cemerlang N, Kiriazis H, Du XJ, Ritchie RH. (2010). Cardiac-
specific IGF-1 receptor transgenic expression protects against cardiac fibrosis and diastolic dysfunction in a
mouse model of diabetic cardiomyopathy. Diabetes 59(6): 1512-1520
2. Ritchie RH, Love JE*, Huynh K*, Bernardo BC, Henstridge D, Kiriazis H, Tham YK, Sapra G, Qin C, Cemerlang N,
Boey EJH, Jandeleit-Dahm KA, Du XJ, McMullen JR. (2012). Enhanced phosphoinositide 3-kinase (p110α)
activity prevents diabetes–induced cardiomyopathy and superoxide generation in a mouse model of diabetes.
Diabetologia 55(12): 3369-3381.
3. Huynh K, Kiriazis H, Du XJ, Love JE, Gray SP, Jandeleit-Dahm KA, McMullen JR*, Ritchie RH*. (2013). Targeting
the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic
cardiomyopathy in mice. Free Rad Biol Med 60: 307-317.
29
Project title: New Cellular Cholesterol Transporter
Laboratory: Lipoproteins and Atherosclerosis
Primary Supervisor (s): Prof. Dmitri Sviridov, Dr. Ying Fu
Contact:
Dmitri.Sviridov @bakeridi.edu.au 8532 1363
Research Focus: Treatment for atherosclerosis and diabetes
Keywords: Atherosclerosis, lipids, diabetes, heart disease, vascular biology
Atherosclerosis is the cause of majority of cardiovascular diseases, a major cause of death in Western
societies. Atherosclerosis is essentially accumulation of excessive cholesterol in the walls of arteries with
the formation of atherosclerotic plaque blocking the blood flow and causing thrombosis. Accumulation of
cholesterol may be caused by excessive delivery of cholesterol from blood or by damaged pathways
responsible for eliminating excess of intracellular cholesterol. Disturbances in intracellular cholesterol
metabolism are the primary cause of impairment of cholesterol release and are on the full front of rapidly
emerging anti-atherosclerotic therapies. Cholesterol homeostasis also plays a key role in diabetes:
accumulation of cholesterol in βcells severely disrupts insulin secretion.
A key element of intracellular cholesterol metabolism is a group of proteins moving cholesterol around
the cell called ABC transporters. ABC transporters regulate release of cholesterol from cells to plasma and
maintain correct intracellular cholesterol content. Surprisingly, very little is known about how these
transporters work.
We have recently discovered that one of the transporters, ABCA12, which was known to play an important
role in skin, also plays an important role in macrophages, cell central for development of atherosclerosis
and inflammation and in βcells. It appears that ABCA12 is responsible for “regulating the regulator” –
modulating a major pathway responsible for coordinate action of other ABC transporters. The same
pathway is also involved in regulation of inflammation. The study is a combination of sophisticated in vitro
study aimed at discovering the molecular and cellular mechanisms of how ABCA12 regulates this pathway,
and in vivo study aimed at testing the effects of ABCA12 deficiency on development of atherosclerosis and
diabetes in mouse model of these diseases. The project is conducted in collaboration with Monash
University.
• Cell biology
• Animal models
References:
1. Fu Y, Mukhamedova N, Ip S, et al. ABCA12 Regulates ABCA1-Dependent Cholesterol Efflux from

Macrophages and the Development of Atherosclerosis. Cell Metabolism. 2013;18:225-38.
2. Smyth I, Hacking DF, Hilton AA, et al. A mouse model of harlequin ichthyosis delineates a key role for
abca12 in lipid homeostasis. PLoS Genet. 2008;4:e1000192.
30
Project title: Cholesterol metabolism and complications of HIV disease
Primary Supervisor (s): Prof. Dmitri Sviridov, Dr. Nigora Mukhamedova
Contact:
Research Focus: Pathogenesis of complications of HIV disease
Keywords: HIV, atherosclerosis, lipids, diabetes, heart disease, vascular biology
Current treatment for HIV infection has dramatically reduced mortality, however, co-morbidities that are
not directly related to immunodeficiency are now increasingly recognized as a consequence of HIV
infection. One such co-morbidity is an increased risk of cardiovascular and metabolic disease. The current
view is that HIV infection and/or its treatment are associated with elevated risk of development of
atherosclerosis and consequently with increased prevalence of acute and chronic cardiovascular events.
HIV also causes disturbances of lipoprotein metabolism, metabolic syndrome, lipodystrophy, dementia.
We currently investigate how HIV is causing co-morbidities in the organs not infected with the virus. Our
hypothesis is that HIV-infected cells release viral proteins and MiRs in the bloodstream that affect
uninfected cells causing pathology in these cells without infection. Our study is focused on establishing
how factors released by HIV-infected cells affect uninfected cells. Our hypothesis, supported by large
volume of data, is a key affected pathway is the pathway related to cholesterol metabolism.
The project is a combination of in vitro work in cell culture, animal studies and some clinical work.
It is on the crossroads of virology and cardiology and gives an opportunity to learn a wide range of
techniques, from cell biology to biochemistry as well as clinical studies. The project is conducted in
collaboration with a number of Australian and overseas laboratories and gives the participants an
exposure to research in various disciplines.
• Cell biology
• Animal models
References:
1. Cui HL, Ditiatkovski M, Kesani R, et al. HIV protein Nef causes dyslipidemia and formation of foam
cells in mouse models of atherosclerosis. FASEB J. 2014; in press.
2. Cui HL, Grant A, Mukhamedova N, et al. HIV-1 Nef mobilizes lipid rafts in macrophages through a
pathway that competes with ABCA1-dependent cholesterol efflux. J Lipid Res. 2012;53:696-708.
3. Mujawar, Z., Rose, H., Morrow, M. P.,et al. (2006) Human Immunodeficiency Virus Impairs
Reverse Cholesterol Transport from Macrophages, PLoS Biology 4, e365.
31
Project title: Apolipoprotein A-I mimetic peptides and Treatment for Heart Disease
Primary Supervisor (s): Prof. Dmitri Sviridov, Dr. Michael Ditiatkovsky
Contact:
Research Focus: Treatment for atherosclerosis
Keywords: Atherosclerosis, lipids, heart disease, vascular biology, animal models
Drugs affecting lipid metabolism have revolutionized treatment of atherosclerosis reducing the risk of
cardiovascular diseases by 30-40%. There is, however, an urgent need for further reduction of the
unacceptably high remaining risk of CVD. A most promising direction is complementing decreasing levels
of the pro-atherogenic lipoproteins (“bad cholesterol”) with increasing levels of the anti-atherogenic
lipoprotein, high density lipoprotein (HDL, “good cholesterol”), i.e. “HDL Therapy”. The efficiency of HDL
therapy critically depends on the method used to for elevate HDL levels. A promising type of HDL therapy
is the use of peptides mimicking the structure of the main protein of HDL, apolipoprotein A-I (apoA-I). One
advantage of these peptides is that their structure can be easily changed to fine-tune their properties.
In the lead up to this project we developed a series of peptides that mimic various anti-atherogenic
properties of HDL. The project has two aims. One is to use various peptides that have one, but not other
anti-atherogenic properties of HDL to determine which properties are most important for the protection
against atherosclerosis. The second aim is to develop a peptide, or a combination of peptides which
manifest most significant anti-atherogenic properties of HDL and can be further developed into a drug.
The project is substantially animal based, involving the infusion of peptides into a mouse model of
atherosclerosis to examine their effect on atherosclerotic plaques. In addition this study will include a
sizable in vitro component; where the effect of peptides on plasma lipoproteins is investigated. The study
is conducted in close collaboration with National Institutes of Health, USA.
• Cell biology
• Animal models
References:
1. Ditiatkovski, M., W. D’Souza, R. Kesani, J. Chin-Dusting, J. B. de Haan, A. Remaley, and D. Sviridov.

2013. An Apolipoprotein A-I Mimetic Peptide Designed with a Reductionist Approach Stimulates
Reverse Cholesterol Transport and Reduces Atherosclerosis in Mice. PLoS ONE 8: e68802.
2. D'Souza, W., J. A. Stonik, A. Murphy, S. J. Demosky, A. A. Sethi, X. L. Moore, J. Chin-Dusting, A. T.
Remaley, and D. Sviridov. 2010. Structure/Function Relationships of Apolipoprotein A-I Mimetic
Peptides: Implications for Antiatherogenic Activities of High-Density Lipoprotein. Circ Res 107:
217-227.
32
Project title: High-density lipoprotein (HDL) effects on cardiac metabolism, inflammation and function
Laboratory: Metabolic & Vascular Physiology
Primary Supervisor (s): Andrew Siebel, Adele Richart, Bronwyn Kingwell
Contact: andrew.siebel@bakeridi.edu.au 8532-1247

bronwyn.kingwell@bakeridi.edu.au 8532-1518
adele.richart@bakeridi.edu.au 8532-1265
Research Focus:
Study of the effects of HDL on cardiac glucose metabolism in the setting of type 2 diabetes
Keywords:
heart disease, glucose metabolism, inflammation, cardiac function, type 2 diabetes
High-density lipoprotein (HDL) is best known for its anti-atherosclerotic and anti-inflammatory actions,
which have prompted development of HDL-raising strategies to combat cardiovascular disease. We have
characterized previously unrecognized mechanisms by which HDL modulates glucose metabolism in both
skeletal muscle and the pancreas. This project extends our discoveries to examine the effects of HDL on
glucose metabolism, inflammatory responses and cardiac function following myocardial
ischaemia/reperfusion injury using in vivo mouse models. Mechanisms will be further interrogated using
cardiac muscle cells. We are also interested in determining whether HDL is cardioprotective in the context
of obesity and type 2 diabetes. Given the escalating prevalence of obesity and type 2 diabetes, and the
associated increase in cardiovascular complications, understanding mechanisms which may lead to new
therapeutic approaches targeting myocardial metabolism, inflammation and function has potential for
significant impact.
Opportunities exist for Honours, Masters and PhD students.
• Cell culture
• Western blotting, qPCR, radiolabelled assays
• In vivo animal handling, surgery, functional analyses and tissue collection
References:
1. Siebel AL, Natoli AK, Yap FY, Carey AL, Reddy-Luthmoodoo M, Sviridov D, Weber CI, Meneses-Lorente G,
Maugeais C, Forbes JM, Kingwell BA. Effects of high-density lipoprotein elevation with cholesteryl ester
transfer protein inhibition on insulin secretion. Circ Res. 2013 Jul 5;113(2):167-75.
2. Carey AL, Siebel AL, Reddy-Luthmoodoo M, Natoli AK, D'Souza W, Meikle PJ, Sviridov D, Drew BG, Kingwell
BA. Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is
prevented by high density lipoprotein. PLoS One. 2013;8(2):e56601.
3. Drew BG, Rye KA, Duffy SJ, Barter P, Kingwell BA. The emerging role of HDL in glucose metabolism. Nat Rev
Endocrinol. 2012 Jan 24;8(4):237-45. Review.
4. Drew BG, Duffy SJ, Formosa MF, Natoli AK, Henstridge DC, Penfold SA, Thomas WG, Mukhamedova N, de
Courten B, Forbes JM, Yap FY, Kaye DM, van Hall G, Febbraio MA, Kemp BE, Sviridov D, Steinberg GR,
Kingwell BA. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes
mellitus. Circulation. 2009 Apr 21;119(15):2103-11.
33
Project title: Development of brown adipose tissue for treatment of obesity
Laboratory: Metabolic & Vascular Physiology
Primary Supervisor (s): Andrew Carey & Bronwyn Kingwell
Contact: andrew.carey@bakeridi.edu.au 8532-1251

bronwyn.kingwell@bakeridi.edu.au 8532-1518
Research Focus:
Study of brown adipose (fat) in humans as a potential treatment for obesity
Keywords:
Obesity, diabetes, fat, brown fat, brown adipose tissue, energy expenditure
Fundamentally, obesity results from an imbalance between energy intake and expenditure. Current
preventative and therapeutic approaches have been either unsustainable or result in significant negative
side effects. Brown adipose tissue (BAT) is unique with respect to its sole function of burning potentially
great quantities of energy, therefore increasing BAT content and activity is currently considered one of the
most promising strategies to increase energy expenditure to combat obesity. BAT function in small
animals is well described, however in humans knowledge is limited due to only recently being conclusively
identified in adults and the identification of novel techniques to measure its activity.
Our ongoing studies therefore provide opportunities to explore the possibility of combating obesity
related disease while gaining broad research experience and skills ranging from clinical research to
numerous wet lab techniques.

Numerous aspects of human clinical research, including
• Volunteer recruitment
• Tissue collection
• Body composition analysis
• Measurement of whole body energy expenditure
• Examination of nuclear medicine scans for BAT activity
• Basic Science/wet laboratory analytical techniques
• Opportunity to discuss your work regularly to both lay people and those involved in research
References:
1. Carey et al. (2013) Diabetologia. 56: 147-55.
2. Carey and Kingwell (2013) Pharmacology and Therapeutics. 140: 26-33
34
Project title:
Role of the brain in a mouse model of neurogenic hypertension
Laboratory:
Neuropharmacology laboratory
Prof Geoff Head, Dr Kristy Jackson and Dr Pamela Davern
Contact:
geoff.head@bakeridi.edu.au 03 8532 1332
kristy.jackson@bakeridi.edu.au 03 8532 1390
pamela.davern@bakeridi.edu.au 03 8532 1330
Research Focus:
The influence of the central nervous system on long-term blood pressure levels and the relationship
between blood pressure and stress pathways in the brain is a major focus of the Neuropharmacology
Lab's studies. Research in Neuropharmacology centres on cardiovascular neuroscience and fills a niche
between the clinic and basic research.
Keywords
Hypertension, brain, immunohistochemistry, pharmacology
The Schlager BPH/2J mice is a model of hypertension which is caused by
overactivity of the sympathetic nervous system (SNS) 1 driven by greater
activity of neurons in the medial amygdala2, a brain region most notable for
its role in stress. The brain regions downstream of the medial amygdala
which result in SNS overactivity likely include projections to the
hypothalamus but to date these pathways have not been assessed.
Part 1 of this student project will determine these downstream brain
pathways involved in causing the hypertension in BPH/2J mice. This will be
achieved by injecting a tracing compound into the medial amygdala and
tracking where in the brain these neurons project using
immunohistochemistry. In particular we will identify brain regions involved
in hypertension by colocalising with another immunohistochemical marker
of neuronal activity (Fos).
Part 2 of this student project will be to pharmacologically inhibit one of the important brain regions
(identified in part one of this study) and measure the effect on blood pressure in conscious BPH/2J mice
via radiotelemetry probes.

• Animal handling and surgery
• Immunohistochemical analysis of brain regions
• Direct measurement of blood pressure in conscious freely moving mice
References:
1. Davern PJ, Nguyen-Huu T, La Greca L, Head GA. Role of the sympathetic nervous system in
Schlager genetically hypertensive mice. Hypertension. 2009; 54(4):852-859.
2. Jackson KL, Palma-Rigo K, Nguyen-Huu T-P, Davern PJ, Head GA. Major contribution of the medial
amygdala to hypertension in BPH/2J genetically hypertensive mice. Hypertension. 2014; 63:811-
818.
35
Project title:
Central mechanisms underlying obesity related hypertension: trans-generational effect on cardiovascular
events
Laboratory:
Prof Geoff Head, Dr Joon Lim (Kyungjoon Lim) and Dr Pamela Davern
Contact:
geoff.head@bakeridi.edu.au 03 8532 1332
joon.lim@bakeridi.edu.au 03 8532 1333
Research Focus:
The influence of the central nervous system on obesity related hypertension and the relationship
between trans-generational effect of obesity and blood pressure. Research in Neuropharmacology
centres on cardiovascular neuroscience and fills a niche between the clinic and basic research.
Keywords
Obesity, Hypertension, Developmental Programming, Brain, Physiology, Pharmacology, Leptin
It is increasingly apparent that the high rate of
hypertension in many societies can be attributed
to an equally alarming rate of obesity. The
sympathetic nervous system (SNS), responsible in
part for control of blood pressure, is known to be
overactive in obese humans. In our laboratory, we
have shown that the levels of plasma insulin and
leptin increase for up to 3 weeks after 1 week of
high-fat feeding, accompanied by elevated blood
pressure and renal sympathetic nerve activity,. This study will investigate changes in leptin and insulin
signalling when rabbits are born from obese mother where breeder rabbits are fed with a high-fat-diet.
This project will involve surgical implantation of an intracerebroventricular catheter (for delivering drugs
directly to the brain) and implantation of a renal sympathetic nerve electrode (nerve activity recording).
Also, immunohistochemistry and real-time PCR will be used to identify the signalling pathways that may
be associated with obesity-related hypertension.

• Direct measurement of blood pressure and renal sympathetic nerve activity in conscious rabbits
References:
1. Kyungjoon Lim, Sandra L. Burke and Geoffrey A. Head (2013). “Obesity related hypertension
and the role of insulin and leptin in high fat fed rabbits” Hypertension 61; 628-634, selected
for evaluation by Faculty of 1000 (F1000), Top 2 % in all Biological & Medical Journals in the
world).
2. Kyungjoon Lim, Sandra L. Burke, James A. Armitage, Geoffrey A. Head (2012). “Comparison of
blood pressure and sympathetic activity of rabbits in their home cage and the laboratory
environment” Experimental Physiology 97 (12):1263, selected for evaluation by Faculty of
1000 (F1000), Top 2 % in all Biological & Medical Journals in the world).
36
Project title:
Central effects of chronic stress and mild activation of the renin angiotensin system on blood pressure
Laboratory:
Prof Geoff Head and Dr Pamela Davern
Contact:
geoff.head@bakeridi.edu.au 03 85321332
pamela.davern@bakeridi.edu.au 03 85321330
Research Focus: The influence of the central nervous system on long-term blood pressure levels and the
relationship between blood pressure and stress pathways in the brain is a major focus of the
Neuropharmacology Lab's studies. Research in Neuropharmacology centres on cardiovascular
neuroscience and fills a niche between the clinic and basic research. Work is carried out to understand the
mechanisms that trigger cardiovascular diseases through environmental factors. Stress is a main area of
investigation and research is also being conducted on the effects on the central nervous system in
response to mild activation of the renin angiotensin system.
Keywords
Hypertension, Chronic stress, Renin angiotensin system, Central nervous system
Project description: The effects of acute stress have been well documented
in the literature but the mechanisms by which chronic stress or repeated daily
exposure to acute stress contributes to sustained elevations in blood pressure
is not well understood. The critical factor leading to a marked amplification of
cardiovascular responses does not appear to arise from chronic stress per se
but requires a combination with either an acute novel stress experience or
low subpressor increases in circulating angiotensin II. Our laboratory has data
that indicates overexpression of neuronal nitric oxide synthase and NADPH
oxidase in neurons that are activated in response to novel stress. This
observation is also associated with elevated blood pressure and identified in brain regions such as the
amygdala and hypothalamus that are known to regulate sympathetic output to influence the kidney. In
this study we will repeatedly expose mice administered a mild dose of angiotensin II or vehicle to a stress
on a daily basis over two weeks and record their blood pressure, heart rate and activity continuously via
radiotelemetry devices. The effect of stress on cardiovascular parameters and neuronal activation and
associated neurochemical signatures will also be determined using immunohistochemistry.

• Stress tests to measure reactivity to aversive and non-aversive stress
References:
1. Davern, P.J., et al., Cardiovascular reactivity and neuronal activation to stress in schlager
genetically hypertensive mice. Hypertension, 2010. 170: 551-558.
2. Davern, P.J., et al., Cardiovascular responses to aversive and non-aversive stressors in schlager
genetically hypertensive mice. American Journal of Hypertension, 2010. 23: 838-844.
37
Project title:
Mechanisms responsible for neuronal synaptic plasticity influencing blood pressure regulation
Laboratory:
Prof Geoff Head, Dr Kristy Jackson and Dr Pamela Davern
Contact:
geoff.head@bakeridi.edu.au 03 85321332
kristy.jackson@bakeridi.edu.au 03 85321390
Research Focus:
The influence of the central nervous system on long-term blood pressure levels and the relationship
between blood pressure and stress pathways in the brain is a major focus of the Neuropharmacology
Lab's studies. Research in Neuropharmacology centres on cardiovascular neuroscience and fills a niche
between the clinic and basic research.
Keywords
Hypertension, brain, synaptic plasticity, tissue plasminogen activator, stress, immunohistochemistry
Tissue plasminogen activator
(tPA) is very highly expressed in
the brain where it is an important
mediator of synaptic plasticity.
One of the brain regions which
displays pronounced expression
of tPA is the medial amygdala
which is a brain region crucial for
regulating cardiovascular
responses to stress and
mediating neurogenic
hypertension in Schalger BPH/2J
mice.1 tPA is likely to play an important role in mediating the maladaptive effects of chronic stress in stress
related brain regions and subsequently contribute to hypertension. Therefore this project aims to
determine whether tPA influences neuronal plasticity in cardiovascular regulatory brain regions such as
the medial amygdala which may ultimately affect blood pressure. Mouse strains genetically modified to
over or under-express tPA will be exposed to chronic stress and a Golgi-Cox staining technique used to
visualize morphological changes in dendritic spines to indicate synaptic plasticity. Immunohistochemistry
will also be used to label for stress hormones and other markers and radiotelemetry devices will record
cardiovascular parameters including blood pressure and heart rate in conscious freely moving mice.

References:
1. Jackson KL, Palma-Rigo K, Nguyen-Huu T-P, Davern PJ, Head GA. Major contribution of the medial amygdala
to hypertension in BPH/2J genetically hypertensive mice. Hypertension. 2014; 63(4):811-818.
38
Project title: The role of caveolae in hypertension-induced inflammation
Laboratory: Vascular Pharmacology
Primary Supervisor (s): Dr Karen Andrews & Professor Jaye Chin-Dusting
Contact: karen.andrews@bakeridi.edu.au 8532 1294
Research Focus: Hypertension induced inflammation, specifically investigating the effect of high blood
pressure on leukocyte adhesion which leads to atherosclerosis.
Keywords: hypertension, inflammation, caveolae, leukocyte adhesion
Project description: Despite the widespread availability of blood pressure lowering medications, high blood
pressure (hypertension) remains responsible for more deaths and disease globally than any other
biomedical risk. While numerous studies identify hypertension as a potent contributing factor in the
development of coronary artery disease (CAD), the exact mechanism by which this occurs is not known. We
have shown that high intraluminal pressure per se causes leukocyte to endothelium adhesion, a hallmark of
vascular inflammation which leads to CAD. We have also shown that high intraluminal pressure alters
caveolae (50- to 100-nm flask-shaped invaginations of the plasma membrane) structure, where pressure
decreases caveolae number (Figure). Caveolae mediate vesicular transport and house many proteins
relating to cholesterol metabolism and cell signaling. This project aims to determine the mechanisms by
which high intraluminal pressure modulates caveolae. The effect of pulsatile pressure on leukocyte
adhesion, using algorithms of blood pressure of hypertensive and normotensive patients, will be
investigated in rat carotid arteries. The effect of pressure on caveolae number and function will be
analysed in vessels subjected to different conditions. These studies may lead to new paradigms in the
management of cardiovascular risk commonly seen in many individuals.
0 mmHg 80 mmHg 120 mmHg
5 **
C a v e o la e n u m b e r /µ m
4
*
3
0 80 120

• Ex vivo: vessel chamber
• Electron microscopy
• Molecular techniques: gene expression via real-time PCR, protein expression via flow cytometry
and western blot analysis
References:
1. Michell DL, Andrews KL, Woollard KJ, Chin-Dusting JP. Imaging leukocyte adhesion to the vascular endothelium at
high intraluminal pressure J Vis Exp. 2011 Aug 23;(54). pii: 3221.
39
Project title: Understanding the energy pathways regulating monocyte subsets and their recruitment to
the atherosclerotic plaque
Primary Supervisor (s): Dr Andrew Murphy and Professor Jaye Chin-Dusting
Contact: andrew.murphy@@bakeridi.edu.au 8532 1292
Research Focus: The effects of atherosclerosis on energy metabolism in monocyte subsets.
Keywords: atherosclerosis, monocytes, energy metabolism
Project description: Cardiovascular disease (CVD) is the leading cause of death worldwide.
Atherosclerosis, a chronic inflammatory disease of the arterial wall is the main contributor of this disease.
This process begins with excess cholesterol depositing into the arterial wall which recruits circulating
monocytes into the sub-endothelial space where they differentiate into macrophages and engulf
cholesterol. When macrophages become overloaded with cholesterol, they are unable to emigrate out of
the vessel wall and thus become trapped, contributing to the atherosclerotic plaque. There are three
subpopulations of circulating blood monocytes (classical – CD14+, intermediate - CD14+/CD16+ & non-
classical – CD16+) and recent clinical observations indicate that of these the non-classical subset is
significantly elevated in patients with CVD. Thus, targeting non-classical monocytes in circulation may hold
key to regressing the atherosclerotic plaque. New evidence now suggests that the energy status of
immune cells in chronic inflammatory diseases such as atherosclerosis plays a critical role and that
manipulating their energy pathways may hold the therapeutic key to the regression of atherosclerotic
plaques. We have shown for the first time that non-classical
monocytes isolated from healthy blood donors meet their
normal energy needs through increased mitochondrial
respiration compared to the classical and intermediate subset
(Figure). Whether their energy metabolism is altered after
exposure to high cholesterol or high glucose, as seen in
atherosclerosis or diabetes, remains to be determined. This
project will involve the use of an atherosclerotic mouse model to
understand how the metabolic requirements of monocyte
subsets differ to healthy control mice, and whether manipulating
their energy pathways may prevent them from entering the sub-
endothelial wall and feeding into the atherosclerotic plaque.

• Flow cytometry
• RT-PCR
• Seahorse extracellular flux analyser
• Transmigration assays
References:
1. Kelly B, O'Neill LA. Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res. 2015
Jul;25(7):771-84.
40
Project title: Exploring mechanisms of T cell mediated vascular inflammation
Primary Supervisor (s): Dr Karen Andrews, Dr Andrew Murphy & Professor Jaye Chin-Dusting
Contact: karen.andrews@bakeridi.edu.au 8532 1294

andrew. murphy@bakeridi.edu.au 8532 1292
Research Focus: To explore how T cells contribute to hypertension.
Keywords: T cells, inflammation, hypertension
Project description: The most common medical ailment managed by physicians globally is high blood
pressure (hypertension) with greater than 2 million Australians diagnosed with this condition. Chronic
high blood pressure is accountable for more deaths and disease globally than any other biomedical risk
(including obesity and diabetes) and is the single biggest contributor to the incidence and progression of
coronary artery disease (CAD), the underlying cause of heart attack and stroke. Inflammation is primarily a
necessary and beneficial defense mechanism against foreign insult (such as germs and bacteria), tissue
damage or injury. It localizes and eliminates the insult while repairing surrounding tissue. However, it is
now thought that inflammation plays a role in the initiation and progression of hypertension and that
vascular inflammation is a significant component of immune-mediated hypertension. As important
recruiters of other white blood cells (leukocytes), T cells are integral drivers of vascular inflammation.
However the mechanisms underlying T cell-driven vascular leukocyte recruitment and inflammation have
not been well-defined. We propose that T cell-mediated activation of endothelial cells is a key driver of
vascular inflammation, through the induction of vascular-derived chemokines and vascular adhesion
molecules. The aim of this project is to determine how T cells perpetuate vascular inflammation, which
may help identify new therapeutic targets for hypertension.
• In vitro: blood vessel organ bath

• Molecular techniques: gene expression via real-time PCR, protein expression via flow cytometry
and/or western blot analysis.
• Migration assays.
References:
1. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C, Harrison DG. Role of the T
cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007 Oct
1;204(10):2449-60.
2. McMaster WG, Kirabo A, Madhur MS, Harrison DG. Inflammation, immunity, and hypertensive end-organ damage.
Circ Res. 2015 Mar 13;116(6):1022-33.
41
Project title: Lipid profiling in acute inflammatory bowel disease
Laboratory: Vascular pharmacology

Prof. Anthony Dart, Dr. Lu Fang, Prof. Jaye Chin-Dusting
Contact:
kfanglu@bakeridi.edu.au 8532 1560
Research Focus:
We aim to examine lipid profiling and inflammation in acute inflammatory bowel disease
Keywords: Lipidomics, inflammation, inflammatory bowel disease
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, encompassing two related and
distinct forms of intestinal inflammation: ulcerative colitis (UC) and Crohn's disease (CD). The
development and course of IBD are affected by several factors, including genetic predisposition, the
intestinal microbiota, other environmental factors and a dysregulated host immune response.1 However,
the precise etiology of IBD remains unknown. Lipid metabolism and signalling are suggested to play
important roles in inflammation with significant implications for IBD. We have recently examined plasma
lipid profiling on patients with IBD at the chronic phase. We have demonstrated that a number of ether
lipids (including alkylphospholipid and plasmalogens), a type of membrane phospholipids, are significantly
and inversely associated with CD, but not with UC.2 Ether lipids possess anti-oxidant properties. Ample
evidence has indicated that oxidant-mediated injury plays an important role in the pathogenesis of IBD.3
The decrease of ether lipids may lead to impaired antioxidant defence, thus contributing to the pathology
of IBD. Since patients in our previous study2 were in remission, we plan to recruit IBD patients with acute
inflammation and examine plasma lipid profiling and inflammatory markers in these patients. We will
compare lipid profiling and inflammatory markers between healthy controls and patients with UC and CD.
• Recruit patients from Alfred Hospital

• Measure inflammatory markers by Elisa assay, and measure microparticles by flow cytometery
• Measure plasma lipids by lipidomics
• Analyze data and perform statistical tests
References:
1. Kaser A, Zeissig S and Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573-621.
2. Fan F, Mundra PA, Fang L, Galvin A, Moore XL, Weir JM, Wong G, White DA, Chin-Dusting J, Sparrow MP, Meikle PJ
and Dart AM. Lipidomic Profiling in Inflammatory Bowel Disease: Comparison Between Ulcerative Colitis and Crohn's
Disease. Inflammatory bowel diseases. 2015;21:1511-8.
3. Karp SM and Koch TR. Oxidative stress and antioxidants in inflammatory bowel disease. Disease-a-month : DM.
2006;52:199-207.
42
Project title: Investigating the therapeutic potential of targeting the bone morphogenetic protein signalling
pathway to combat skeletal muscle wasting
Laboratory: Muscle Research and Therapeutics
Primary Supervisor(s): Dr Paul Gregorevic
Contact: email: paul.gregorevic@bakeridi.edu.au phone: 8532 - 1224

Research Focus: Developing molecular interventions to dissect mechanisms controlling skeletal muscle
attributes and generate gene therapies for conditions of muscle wasting.
Keywords: Skeletal muscle, cell signaling, growth regulation, gene therapy, wasting, cancer cachexia,
sarcopenia, muscular dystrophy, aging.
Skeletal muscle comprises approximately 40% of our body mass and performs a number of crucial bodily
functions. Loss of muscle mass and strength is a serious and unmet health risk associated with disability,
illness and premature death, having serious consequences on the vast majority of society.
The Laboratory for Muscle Research and Therapeutics Development aims to identify the molecular
mechanisms that control muscle mass and manipulate cellular signalling pathways to promote muscle
hypertrophy, metabolic function and strength in disease.
Our lab specialises in the delivery of genes to the striated muscle using recombinant viral vectors. This
cutting edge technology allows us to reveal the basic biological characteristics of skeletal muscle in vivo in
addition to providing a platform to investigate gene therapies in mouse models of skeletal muscle wasting1.
A particularly novel signalling pathway controlling skeletal muscle mass is the bone morphogenetic protein
(BMP) signaling pathway which was originally discovered for its role in stimulating bone formation. We
have recently shown that this pathway plays a vital role as a positive regulator of skeletal muscle mass 2.
Increasing BMP signaling in muscle can promote muscle growth, and counter protein breakdown 2,3. Based
on these exciting results, we are now seeking to investigate whether gene-delivery and drug based
interventions can be developed which target this pathway, as new therapeutics for muscle wasting.
The central aim of this project will be to use a number of molecular approaches to increase or reduce BMP
signalling in skeletal muscle and accompanying cell types in mouse models of disease, to determine if this
impacts on the loss of muscle mass associated with muscle wasting conditions, and impacts on lifespan.
Additional studies will examine the signaling and gene regulation associated with these effects. Research
projects are available for Honours, Masters and PhD students.
Viral vector
delivery Preservation
Healthy
Healthy Nerve
Nerve damage
damage
Muscle
Muscle
of muscle
Muscle
Muscle wasting
wasting
Activation
Activation of of Up-regulation of mass
musclecatabolism
muscle catabolism BMPs
43
• Analysing skeletal • Cell culture validation • Molecular assays

muscle phenotypes in of viral vector including western
vivo plasmids blotting and q-PCR
• Designing and • Using multiple mouse • Histological analysis

administering viral models of skeletal of mouse skeletal
vectors in vivo muscle wasting muscle
• Immunofluorescent • Physiological
microscopy assessment of
skeletal muscle
function
References:
1. Gregorevic et al rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic
mice. Nat Med. 2006 Jul;12(7):787-9.
2. Winbanks et al The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass. J Cell Biol. 2013
Oct 28;203(2):345-57.
3. Sartori et al BMP signaling controls muscle mass. Nat Genet. 2013 Nov;45(11):1309-18.
44
Project title: Using gene therapy tools to study and treat skeletal muscle disease
Laboratory: Muscle Research and Therapeutics
Primary Supervisor(s): Dr Paul Gregorevic
Contact: email: paul.gregorevic@bakeridi.edu.au phone: 8532 - 1224

Research Focus: Developing molecular interventions to understand mechanisms controlling skeletal
muscle attributes and treat conditions of muscle wasting
Keywords: Skeletal muscle, cell signaling, growth regulation, gene therapy, wasting, cancer cachexia,
sarcopenia, muscular dystrophy, aging.
Physical frailty caused by loss of skeletal muscle mass and strength is one of the main factors contributing
to disability, illness and premature death worldwide. Our goal is to elucidate how the cellular mechanisms
that regulate muscle development and adaptation become perturbed in muscle wasting, and to develop
new therapeutic approaches to reverse loss of muscle mass, strength and metabolic function.
What sets us apart is that we design and make recombinant viral vectors “in-house”, to regulate and
interrogate the cellular mechanisms controlling muscle adaptation in vivo with a combination of precision,
efficacy, and speed not offered by other methods. Our expertise in using gene delivery technologies to
manipulate muscle1 is unparalleled in Australia, and undertaking research with us provides a unique
opportunity to work with these cutting edge methods.
Opportunities are available to conduct studies within several of our research themes:
• How does the Transforming Growth Factor-β signalling network regulate muscle 2,3
• Novel genes that control skeletal muscle growth and wasting 4
• Using vector-based delivery of genome editing technology to study and treat disease
• Novel gene therapies for neuromuscular disorders, and wasting in chronic illness
• Using gene therapies to treat diabetes & diabetic complications.
Students are also welcome to discuss other projects that may fall outside of these themes, or involve
building collaborations with other teams possessing complementary expertise. Research projects are
available for Honours, Masters and PhD students.
Figure 1: Recombinant viral vectors can be used as gene delivery tools to study the regulation of muscle attributes, and potentially to treat
conditions associated with skeletal and cardiac muscle disease.
45
• Analysing skeletal • Cell culture validation • Molecular assays

muscle phenotypes in of viral vector including western
vivo plasmids blotting and q-PCR
• Designing and • Using multiple mouse • Histological analysis

administering viral models of skeletal of mouse skeletal
vectors in vivo muscle wasting muscle
• Immunofluorescent • Physiological
microscopy assessment of
skeletal muscle
function
References:
mice. Nat Med. 2006 Jul;12(7):787-9.
2. Winbanks et al The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass. J Cell
Biol. 2013 Oct 28;203(2):345-57.
3. Winbanks et al Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently
of myostatin. J Cell Biol. 2012 Jun 25;197(7):997-1008.
4. Chen et al Elevated expression of activins promotes muscle wasting and cachexia. FASEB J. 2014 Apr;28(4):1711-
23.
46
Project title: Regulation of skeletal muscle mass in health and disease
Laboratory: Muscle biology and therapeutics
Primary Supervisor(s): Dr Paul Gregorevic and Dr Kevin Watt
Contact: email: paul.gregorevic @bakeridi.edu.au phone: 8532-1224

Research Focus: Signalling pathways regulating skeletal muscle size, mechanisms promoting skeletal
muscle atrophy in neuromuscular disease
Keywords: skeletal muscle, hypertrophy, atrophy,

Physical frailty caused by loss of skeletal muscle mass and strength is one of the main
factors contributing to disability, illness and premature death worldwide. The goal of our laboratory is to
elucidate how the cellular mechanisms that regulate muscle development and adaptation
become perturbed in muscle wasting, and to develop new therapeutic approaches to reverse
loss of muscle mass, strength and metabolic function.
To do this we design and make recombinant viral vectors as a means to regulate and interrogate the
cellular mechanisms controlling muscle adaptation in vivo with a combination of precision, efficacy, and
speed not offered by other methods (Fig 1). Our expertise in using gene delivery technologies in skeletal
muscle 1,2 is unparalleled in Australia, and undertaking research with us is a unique opportunity to work
with cutting edge methodology.
Fig1. Schematic of rAAV production and Fig2. Schematic representation of the human
application in vivo Hippo signalling pathway (Harvey et al 3)
This project will interrogate the role of the Hippo signalling pathway (Fig 2) as a novel regulator of skeletal
muscle size in health and disease. This pathway is currently generating much study with numerous
examples of publications in the very highest impact journals. The Hippo signalling pathway is also a key
regulator of skeletal muscle size. However, the mechanisms that drive this remain unclear. Using gene
delivery technologies and a number of disease relevant models e.g. cancer cachexia and amyotrophic
lateral sclerosis we will assess the interactions between the Hippo signalling network, and other key
signalling pathways, as mechanisms governing skeletal muscle size in health and disease. Research
projects are available for Honours, Masters and PhD students.
47
• Range of molecular biology methods (Western blotting, q-RT-PCR, Histology, Cell culture, In vivo
manipulation of gene expression)
• Design, manufacture and administration in vitro and in vivo of recombinant viral vectors.
• Animal models of disease. Small animal handling, and surgical procedures.
References:
mice. Nat Med. 2006 Jul;12(7):787-9.
2. Winbanks et al The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass. J Cell
Biol. 2013 Oct 28;203(2):345-57.
3. Harvey K.F, Zhang X., Thomas D.M. The Hippo pathway and cancer. Nat Rev Cancer 2013 Apr;13(4):246-57
48

2016 Student Projects - Sept - Final PDF

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Student Research Projects in

Cardiovascular Disease, Diabetes &

Index of Projects by Laboratory

Cardiac Hypertrophy .................................................................................................. 5

Cellular & Molecular Metabolism............................................................................... 9

Diabetes & Dyslipidaemia ........................................................................................ 11

Heart Failure Research ............................................................................................. 22

Heart Failure Pharmacology ..................................................................................... 24

Lipoproteins & Atherosclerosis ................................................................................ 30

Metabolic & Vascular Physiology ............................................................................. 33

Vascular Pharmacology ............................................................................................ 39

Muscle Biology & Therapeutics ................................................................................ 43

Laboratory: Aboriginal Health

Primary Supervisor (s) Sandra Eades, Catherine Chamberlain

Contact: Catherine.chamberlain@bakeridi.edu.au 8532 1207

Project related methods/skills/technologies:

Laboratory: Aboriginal Health

Primary Supervisor (s)

Research Focus: Health and wellbeing of Aboriginal adolescents

Project related methods/skills/technologies:

• Epidemiology and biostatistics

Laboratory: Cardiac Hypertrophy

Primary Supervisor (s) Dr Bianca Bernardo and A/Prof Julie McMullen

Keywords: heart failure, fibrosis, tilorone, novel therapies

Project related methods/skills/technologies:

• Experimental mouse procedures (echocardiography, dissection, i.p. injections)

1. Lepperantra et al., 2013 Am J Respir Cell Mol Biol 48:448-55

Laboratory: Cardiac Hypertrophy

Primary Supervisor (s) A/Prof Julie McMullen

Keywords: heart, cardiac function & rhythm, PI3K signalling

Project related methods/skills/technologies:

• Experimental mouse procedures (echocardiography, ecg, dissection)

Laboratory: Cardiac Hypertrophy

Primary Supervisor (s) A/Prof Julie McMullen and Dr Jenny Ooi

Keywords: heart, cardiac function & rhythm, anti-cancer agents

Project related methods/skills/technologies:

• Experimental mouse procedures (echocardiography, dissection, i.p. injections)

Laboratory: Cardiac Hypertrophy

Primary Supervisor (s) Dr Jenny Ooi, A/Prof Julie McMullen

Contact: Julie.mcmullen@bakeridi.edu.au, 85321194

Keywords Cardiac hypertrophy, bioinformatics, microRNAs, noncoding RNAs

Project related methods/skills/technologies:

Laboratory: Cellular and Molecular Metabolism Laboratory

Primary Supervisor (s) Darren Henstridge, Mark Febbraio

Contact: darren.henstridge@bakeridi.edu.au 8532 1708

Project related methods/skills/technologies:

Laboratory: Cellular and Molecular Metabolism Laboratory / Diabetes & Dyslipidaemia

Contact: darren.henstridge@bakeridi.edu.au 8532 1708

Project related methods/skills/technologies:

Project related methods/skills/technologies:

• Western blotting – assessment of metabolic signaling pathways

1. Zelcer et al, Transgenic expression of dominant-active IDOL in liver causes diet-induced

Laboratory: Diabetes & Dyslipidaemia Laboratory (DDL)

Primary Supervisor (s) Brian Drew, Anna Calkin

Contact: Brian.drew@bakeridi.edu.au, Ph: 8532 1134

Keywords: energy metabolism, mitochondria, obesity, diabetes, neurodegeneration

Project related methods/skills/technologies:

1. Riera CE at al., Nat Cell Biol, 2015

Project related methods/skills/technologies:

• Molecular biology – cloning, generation of adenovirus, expression constructs

1. Calkin et al, Transgenic expression of dominant-active IDOL in liver causes diet-induced

Laboratory: Diabetic Complications

Project related methods/skills/technologies: