Gopal Chandra Kundu

November 2, 1959 Born Bataspur, West Bengal

Residence

Pune, Maharashtra

Nationality Indian

Fields

Cancer Biology

Institution

National Centre for Cell Science, Pune

Known for

Cancer Models in Animal, Cancer Therapeutics, Biomarker Study for Cancer Detection, Angiogenesis and Nanomedicine

DBT National Bioscience Award, Shanti Swarup Bhatnagar Prize, International

Notable awards

Journal of Oncology, Oncology Reports and International Journal of Molecular Medicine Award for an outstanding

achievement in Oncology, Greece.

Dr. Gopal Kundu has obtained his Ph.D. from Bose Institute, Kolkata, India (1989) in Protein Biochemistry. He did his post-doctoral research work at The Cleveland Clinic Foundation, University of Colorado, University of Wyoming, and The National Institutes of Health, USA from 1989 to 1998. He has performed excellent work in the area of cardiovascular biology, inflammation and immunomodulation during that period. In 1998, he joined as Scientist-D at National Centre for Cell Science (NCCS), India. At present, he is working as Scientist-F at NCCS. His area of research at NCCS is tumor biology, regulation of gene expression, cell signaling, angiogenesis, cancer therapeutics, biomarker study for cancer detection and nanomedicine which earned him many national and international laurels. These works from Dr. Kundus laboratory have been published in several high impact factor peer reviewed journals including Cancer Research, JBC, Trends in Cell Biology, Current Molecular Medicine and Expert Opinion on Therapeutic Targets etc. These works are recognized internationally by several groups in these areas and the papers published based on these works from Dr. Kundus laboratory are highly cited. Dr. Kundu has also published a large number of papers including Nature Medicine, Science, PNAS, JBC etc during his post doctoral research work in USA. The impact factor, citation and based on the citations, the H-index of Dr. Kundus publications are very high (25.00) as compared to any other scientists at National Centre for Cell Science, Pune as well as many other recognized life scientists in India. He has received several awards including Fellows Award for Research Excellence (FARE) from The National Institutes of Health, USA, National Bioscience Award, DBT,

Govt. of India and Shanti Swarup Bhatnagar Prize in Biological Sciences, CSIR, Govt. of India. He has recently received International Award for outstanding achievement in oncology. He is Fellow of National Academy of Sciences, India and Indian Academy of Sciences. He is member of American Society for Biochemistry and Molecular Biology and New York Academy of Sciences. He has published 56 papers in peer reviewed international journals and one US patent. He serves as Editorial Board Member of Current Molecular Medicine, Molecular Medicine Reports, The Open Cancer Journal and American Journal of Cancer Research. He reviewed papers from various journals including Nature, Nature Reviews Cancer, JNCI, MCB, JBC, Cancer Research, Clinical Cancer Research, Expt. Cell Res., Mol. Cancer Therapeutics, Carcinogenesis, Gastroenterology, FASEB J, Eur. J. Cancer, Oncogene, Life Sciences, BMC Cancer, JCMM, Lab. Invest., Intl. J. of Cancer, BBRC and grant proposals from Wellcome Trust UK, Cancer Research UK, MRC UK and Health Research Board (HRB), Ireland.

Regulation of Gene Expression, Signal Transduction, Extracellular Matrix, Tumor Biology, Angiogenesis, Cancer Therapeutics, Biomarker Study for Cancer Detection and Nanomedicine Recent studies from Dr. Kundus laboratory demonstrated that osteopontin can act as potential diagnostic and prognostic marker in various cancers including breast. Dr. Kundu and his group have recently demonstrated that cancer research is focused on the paradigm that tumor progression involves an intricate crosstalk between tumors and stromal environment. His research is primarily focused on delineating the molecular mechanisms by which tumor and stroma-derived osteopontin (OPN), a cytokine like SIBLING family of calcified ECM-associated protein plays an important role in determining the oncogenic potential of various cancers. The results revealed that both stroma and tumor derived OPN regulates a series of signaling events through activation of various signaling molecules that ultimately control the expression of downstream effector genes, which contribute to tumor progression and angiogenesis. Moreover, the functional role of intracellular and secretory OPN as well as the role of various splice variants of OPN in regulating stroma-tumor interaction leading to tumor angiogenesis is

in progress. Several lines of evidences revealed that epithelial to mesenchymal transition plays crucial role in controlling tumor growth and metastasis. The role of OPN in regulation of epithelial to mesenchymal transition and its correlation to breast cancer progression and angiogenesis is being studied in our laboratory. Furthermore, OPN is not only associated with several tumor types, but its level of expression directly correlates to various stages of cancers. The findings from his laboratory have made seminal contribution that highlight the potential role of both tumor and stroma-derived OPN and the molecular mechanism underlying the genesis of tumor progression which may be useful in developing targeted therapy for the treatment of cancer. Current Projects

Role of splice variants, secretory and intracellular OPN in regulation of stromatumor interaction leading to tumor angiogenesis, tumor cell invasion and metastasis. Role of OPN and v3 integrin in epithelial to mesenchymal transition and its correlation to tumor growth and metastasis Studies on peptide nanoparticle-mediated drug/siRNA delivery to tumor vasculature regulates tumor growth and angiogenesis using in vitro and in vivo model and it's analysis by In Vivo Imaging System (IVIS) Development of novel diagnostic and prognostic clinical biomarkers in breast cancer. List of Publications

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Kundu GC and Sinha NK: Purification and characterization of proteinase inhibitor from artocarpus integrifolia seeds. Phytochemistry 28:725-728, 1989. Sen S, Kundu GC, Castel J, Mekhail N, Misono KS and Healy B: Myotrophin: Purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth. J. Biol. Chem. 265 (27): 16635-16643, 1990. Kundu GC and Misono KS: Affinity labeling of endothelin receptors in bovine and rat lung membranes by N9- azidobenzoyl-125 I-endothelin-1. Mol. and Cell. Endocrinology 79: 85-92, 1991. Kundu GC and Wilson IB: Identification of endothelin converting enzyme in bovine lung membranes using a new fluorogenic substrate. Life Sciences 50(13): 965-970, 1992.

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Kundu GC and Wilson IB : Endothelin converting enzyme: the binding of metal ions. Int. J. Peptide and Protein Res. 42(1): 64-67, 1993. Kundu GC, Schullek JR and Wilson IB: The alkylating properties of chlorambucil. Pharmacol. Biochem. Behav. 49(3): 621-624, 1994. Kundu GC, Ji I, McCormick DJ, and Ji TH: Photoaffinity labeling of the lutropin receptor with synthetic peptide for carboxyl terminus of the human choriogonadotropin subunit. J. Biol. Chem. 271(19): 11063-11066, 1996. Kundu GC, Mantile G, Miele L, Cordela-Miele E and Mukherjee AB: Recombinant human uteroglobin suppresses cellular invasiveness via a novel class of high-affinity cell surface binding site. Proc. Natl. Acad. Sci. USA 93: 2915-2919, 1996. Kundu GC and Mukherjee AB: Evidence that porcine pancreatic phospholipase A2 via its high-affinity receptor stimulates extracellular matrix invasion by normal and cancer cells. J. Biol. Chem. 272(04), 2346-2353, 1997. Shanmugam V, Chackalaparampil I, Kundu GC, Mukherjee AB and Mukherjee BB: Altered sialylation of osteopontin prevents its receptor-mediated binding on the surface of oncogenically transformed tsB77 cells. Biochemistry 36(19), 5729-5738, 1997. Zhang Z, Kundu GC, Yuan C-J, Ward JM, Lee EJ, DeMayo F, Westphal H and Mukherjee AB: Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin. Science 276,1408-1412, 1997. Kundu GC, Panda D, Lee BI, Peri A, Fohl D, Chackalaparampil I, Mukherjee BB, Li XD, Mukherjee DC, Seides S, Rosenberg J, Stark K and Mukherjee AB: Potential roles of osteopontin and v3 integrin in the development of coronary artery restenosis after angioplasty. Proc. Natl. Acad. Sci. USA 94, 9308-9313, 1997. Phang T, Kundu GC, Hong S, Ji I and Ji TH: The amino terminal region of the luteinizing hormone/choriogonadotropin receptor contacts both subunits of human choriogonadotropin: II Photoaffinity labeling. J. Biol. Chem. 273(22), 13841-13847, 1998. Kundu GC, Mandal A, Zhang Z, Mantile-Selvaggi G and Mukherjee AB: Uteroglobin suppresses extracellular matrix invasion by normal and cancer cells that express the high affinity UG-binding proteins. J. Biol. Chem. 273 (35), 22819-22824, 1998. Mukherjee AB, Kundu GC, Mandal AK, Pattabiraman N, Yuan C-J and Zhang Z: Uteroglobin(UG): Physiological role in normal glomerular function, uncovered by targeted disruption of the UG gene in mice. Am. J. Kid. Dis. 32 (6), 1106-1120, 1998. Kundu GC, Zhang Z, Panda D, Mandal A.K., Mantile-Selvaggi Peri A, Yuan C-J and Mukherjee AB: Loss of transformed phenotype in cancer cells by over expression of uteroglobin gene. Proc. Natl. Acad. Sci. USA 96, 3963-3968, 1999.

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Mukherjee AB, Kundu GC, Mantile-Selvaggi G, Yuan C-J, Mandal AK, Chattopadhyay S, Zhang F, Pattabiraman N and Zhang Z: Uteroglobin: A novel cytokine? Cell Mol Life Sci. 55(5), 771-87, 1999. Kundu GC, Zheng F, Zhang Z, Ward JM, DeMayo F, Mukherjee AB: An essential role of uteroglobin in preventing immunoglobulin A-nephropathy in mice. Nature Medicine 5(9), 1018-1025, 1999. Zheng F, Kundu GC, Zhang Z, Mukherjee AB, Ward J and DeMayo F: Identical glomerulopathy in two different mouse models of uteroglobin deficiency. Am. J. Kid.Dis. 35(2), 362-363, 2000 20. Zhang Z, Kundu GC, Zheng F, Yuan C-J, Lee E, Westphal H, Ward J, DeMayo F and Mukherjee AB: Insight into the physiological function(s) of uteroglobin by gene knockout and antisense-transgenic approaches. Annals of the New York Academy of Sciences. 923, 210-233, 2000.

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Choudhury B, Mantile-Selvaggi G, Kundu GC, Miele L, Cordella-Miele E, Zhang Z, Mukherjee AB: Amino acid residues in alpha-helix-3 of human uteroglobin are critical for phospholopase A2 inhibitory activity. Annals of the New York Academy of Sciences. 923, 307--311, 2000. Kundu GC, Zhang Z, Mantile-Selvaggi G, Mandal A, Yuan C-J and Mukherjee AB: Uteroglobin binding proteins: regulation of cellular motility and invasion in normal and cancer cells. Annals of the New York Academy of Sciences. 923, 234-248, 2000. Publications from NCCS, Pune, India (2001-till date)

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Philip S, Bulbule, A and Kundu GC: Osteopontin stimulates tumor growth and activation of pro-matrix metalloproteinase-2 through NF-kappa B mediated induction of membrane type 1-matrix metalloproteinase in murine melanoma cells. J. Biol. Chem. 276 (48), 44926-44935, 2001. Annie Bligh SW, Bashall A, Garrud C, McPartlin M, Wardle N, White K, Padhye S, Barve V and Kundu GC: Reaction of (C-(6-aminomethyl-pyridin-2-yl)-methylamine) chloroplatinum (II) with nucleosides and its biological activity. Dalton Transaction, 2, 184-188, 2003. Mahabeleshwar GH and Kundu GC: Syk, a protein tyrosine kinase, suppresses the cell motility and NF-kappa B mediated secretion of urokinase type plasminogen activator by inhibiting the phosphatidylinositol 3-kinase activity in breast cancer cells. J. Biol. Chem. 278 (8), 6209-6221, 2003. Philip S and Kundu GC: Osteopontin induces NF-kappa B mediated promatrix metalloproteinase-2 activation through IKK/I B signaling pathways and curcumin

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(diferulolylmethane) down regulates these pathways. J. Biol. Chem. 278 (16), 1448714497, 2003. 27. Takada Y, Mukhopadhyay A, Kundu GC, Mahabeleshwar GH, Singh S, and Aggarwal BB: Hydrogen peroxide activates NF- B through tyrosine phosphorylation of I B and serine phosphorylation of p65: Evidence for the involvement of I B kinase and Syk protein tyrosine kinase. J. Biol. Chem. 278 (26), 24233-24241, 2003. Das R, Mahabeleshwar GH and Kundu GC: Osteopontin stimulates cell motility and NFB mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J. Biol. Chem. 278 (31), 28593-28606, 2003. Mahabeleshwar GH and Kundu GC: Tyrosine kinase, p56lck regulates cell motility and NF- B-mediated secretion of urokinase type plasminogen activator through tyrosine phosphorylation of I B following hypoxia/reoxygenation. J. Biol. Chem. 278 (52), 52598-52612, 2003. 30. Mahabeleshwar GH, Das R and Kundu GC: Tyrosine kinase, p56lck-induced cell motility and urokinase type plasminogen activator secretion involves activation of epidermal growth factor receptor/extracellular signal regulated kinase pathways. J. Biol. Chem. 279 (11), 9733-9742, 2004 31. Philip S, Bulbule A and Kundu GC: Matrix metalloproteinase-2: mechanism and regulation of NF- B-mediated activation and its role in cell motility and ECM-invasion. Glycoconjugate J. 21, 429-441, 2004. Das R, Mahabeleshwar GH and Kundu GC: Osteopontin induces AP-1-mediated secretion of urokinase type plasminogen activator through c-Src dependent EGF receptor transactivation in breast cancer cells. J. Biol. Chem. 279 (12), 11051-11064, 2004. Rangaswami H, Bulbule A and Kundu GC: Nuclear factor inducing kinase plays crucial role in osteopontin induced MAPK/IKK dependent nuclear factor B-mediated promatrix metalloproteinase-9 activation. J. Biol. Chem. 279 (37), 38921-38935, 2004. Sandbhor U, Kulkarni P, Padhye S, Kundu GC, Mackenzie G and Pritchard R: Antimelanomal activity of the copper (II) complexes of 1-substituted 5-amino imidazole ligands against B16F10 mouse melanoma cells. Bioorg. Med. Chem. Lett. 14(11), 2877-2882, 2004. Das R, Philip S, Mahabeleshwar GH, Bulbule A and Kundu GC: Osteopontin: its role in regulation of cell motility and nuclear factor B-mediated urokinase type plasminogen activator expression. IUBMB Life 57 (6), 441-447, 2005.

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Rangaswami H, Bulbule A and Kundu GC: Osteopontin: role in cell signaling and cancer progression. Trends in Cell Biol. 16 (2), 79-87, 2006. Chakraborty G, Rangaswami R, Jain S, and Kundu GC: Hypoxia regulates crosstalk between Syk and Lck leading to breast cancer progression and angiogenesis. J. Biol. Chem. 281 (16), 11322-11331, 2006. Jain S, Chakraborty G and Kundu GC: The Crucial Role of cyclooxygenase-2 in osteopontin-induced PKC/c-Src/IKK/ dependent prostate tumor progression and angiogenesis. Cancer Res. 66 (13), 6638-6648, 2006 Chakraborty G, Jain S, Behera R, Ahmed M, Sharma P, Kumar V and Kundu GC: The multifaceted roles of Osteopontin in cell signaling, tumor progression and angiogenesis. Curr. Mol. Med. 6 (8), 819-830, 2006 Jain S, Chakraborty G, Bulbule A, Kaur R and Kundu GC: Osteopontin: an emerging therapeutic target for anticancer therapy. Expert Opin. Ther. Targets 11(1), 81-90, 2007 Rangaswami H, Kundu GC.Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncol. Rep. 18 (4):909-15, 2007. Chakraborty et al. Osteopontin regulated signaling network in cancer: redefining the molecular targets. Intl. J. Mol. Med. 20 (Suppl 1), S75, 2007. Chakraborty G, Jain S and Kundu GC: Osteopontin promotes VEGF dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res. 68 (1), 152-161, 2008. Chakraborty G, Jain S, Patil TV and Kundu GC: Down-Regulation of Osteopontin Attenuates Breast Tumor Progression in vivo. J. Cell. Mol. Med., 12 (6A), 2305-2318, 2008 . Chakraborty G, Jain S, Kale S, Raja R, Kumar S, Mishra R and Kundu GC: Curcumin suppresses breast tumor angiogenesis by abrogating osteopontin-induced VEGF expression. Mol Med Reports., 1 (5), 641-646, 2008 (selected for cover page). Jain S, Chakraborty G, Raja R, Kale S, and Kundu GC: Prostaglandin E2 regulates tumor angiogenesis in prostate cancer. Cancer Res, 68(19):77507759, 2008. Seth D, D'Souza El-Guindy NB, Apte M, Mari M, Dooley S, Neuman M, Haber PS, Kundu GC, Darwanto A, de Villiers WJ, Vonlaufen A, Xu Z, Phillips P, Yang S, Goldstein D, Pirola RM, Wilson JS, Moles A, Fernndez A, Colell A, Garca-Ruiz C,

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Fernndez-Checa JC, Meyer C, Meindl-Beinker NM. Alcohol, Signaling, and ECM Turnover. Alcohol Clin Exp Res. 34 (1), 4-18, 2010. 48. Behera R, Kumar V, Lohite K, Karnik S and Kundu GC: Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis, 31 (2), 192-200, 2010. Ahmed M and Kundu GC: Osteopontin selectively regulates p70S6K/mTOR phosphorylation leading to NF-kappa B dependent AP-1-mediated ICAM-1 expression in breast cancer cells. Molecular Cancer 9(1), 101, 2010. Singh JP, Tamang S, Rajamohanan PR, Jima NC, Chakraborty G, Kundu GC, Gaikwad SM, Khan MI: Isolation, Structure, and Functional Elucidation of a Modified Pentapeptide, Cysteine Protease Inhibitor (CPI-2081) from Streptomyces Species 2081 that Exhibit Inhibitory Effect on Cancer Cell Migration. J. Med Chem, June 16, 2010. Sharma P, Kumar S and Kundu GC: Transcriptional regulation of human osteopontin promoter by histone deacetylase inhibitor, trichostatin A in cervical cancer cells. Molecular Cancer, July 7, 9(1), 178, 2010. Pradhan S, Mishra R, Sharma P and Kundu GC: Quercetin and sulforaphane in combination suppress the melanoma progression through down regulation of matrix metalloproteinase-9. Experimental and Therapeutic Medicine, 1, 915-920, 2010. Kumar V, Behera R, Lohite K, Karnik S and Kundu GC: p38 Kinase is Crucial for Osteopontin-induced Furin Expression that Supports Cervical Cancer Progression. Cancer Research, 70 (24), 10381-10391, 2010. Bulbule A, Saraswati Sand Kundu GC: Status of research on matrix metalloproteinases (MMPs) in India. Expert Opin Ther Targets. 2011 Apr 11. [Epub ahead of print] Prakash M. et al. Hyaluronan-Binding Protein 1 (HABP1/p32/gC1qR) Induces Melanoma Cell Migration and Tumor Growth by NF-kappa B Dependent MMP-2 Activation through integrin v3 interaction. Cellular Signalling. 2011 (in press). Ahmed et al. Osteopontin: a potentially important therapeutic target in cancer. Expert Opin Ther Targets. 2011 (in press).

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List of patents: (i) A. B. Mukherjee (Brookeville, MD, USA); G. C. Kundu (Maharashtra, India) and D. Panda (Montreal, Canada): 2002, Methods and compositions for treatment of restenosis. US Patent No. US 6,458,590 B1

Earlier Ph. D. Students: 1. Dr. Subha Philip 2. Dr. Ganapati Mahabeleshwar 3. Dr. Riku Das 4. Dr. Hema Rangaswami 5. Dr. Goutam Chakraborty 6. Dr. Shalini Jain 7. Dr. Mansoor Ahmed 8. Dr. Reeti Behera 9. Dr. Vinit Kumar
CurrentStudents:

1. Priyanka Sharma (Thesis submitted) 2. Rajinder Kaur (Thesis submitted) 3. Smita Kale 4. Remya Raja 5. Santosh Kumar 6. Rosalin Mishra 7. Dhanashri Thorat 8. Gowrishankar S. 9. Dhiraj Kumar 10. Pompom Ghosh 11. Amit Jadav 12. Anuja Ramdasi 13. Megha Sanyal 14. Pradnya Surve (Project Assistant) Project Students (2010-2011): 1. Ms. Amruta Oak 2. Ms. Chaitali Basole Technician-C: 1. Anuradha Bulbule