.

  

Dr. Gopal C. Kundu

Scientist 'F',

National Centre for Cell Science,

NCCS Complex, Pune University Campus

Ganeshkhind, Maharashtra,

Pune- 411007, India

Phone:   +91-20-25708000 Extn. 8103

                 +91-20-25708103

Fax:        +91-20-25692259

Email: kundu@nccs.res.in; gopalkundu@hotmail.com

 

 

 

Research Area and Interest

Regulation of Gene Expression, Signal Transduction, Tumor Biology and Angiogenesis

Recent advancement in cancer research focused on the paradigm that tumor progression involves an intricate crosstalk between tumors and stromal environment. Our research primarily focuses on delineating the molecular mechanisms by which tumor and stroma-derived osteopontin (OPN), a chemokine like SIBLING family of calcified ECM-associated protein plays an important role in determining the oncogenic potential of various cancers. We have demonstrated that OPN regulates tumor growth through induction of COX-2, uPA and VEGF expressions and activation of matrix metalloproteinase (MMP) in various cancer cells. We have recently shown that JAK/STAT3 pathway is directly involved in regulation of breast tumor growth in response to OPN. Our results revealed that 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 in in vitro and animal models. Moreover, OPN is not only associated with several tumor types, but its level of expression directly correlates to various stages of breast cancers. The findings from our 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.

 

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                                                                                                      Current Projects

1. Understanding the mechanism of tumor growth and angiogenesis by osteopontin and other associated genes in breast and other cancers
2. Identification of novel targets and development of target based therapy in cancers
3. Nanomedicine based drug delivery in breast cancer; Development of  multiple tumor models in mice and analysis of tumors by In Vivo Imaging System (IVIS)
4. Development of novel diagnostic and prognostic biomarkers in breast cancer

 

Papers Published from NCCS, Pune (2001-2009)

1.

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, (November), 2009.  
2.

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, Fernández A, Colell A, García-Ruiz C, Fernández-Checa JC, Meyer C, Meindl-Beinker NM. Alcohol, Signaling, and ECM Turnover. Alcohol Clin Exp Res. (October), 2009.

3.

Jain S, Chakraborty G, Raja R, Kale S, and Kundu GC: Prostaglandin E2 regulates tumor angiogenesis in prostate cancer. Cancer Res, 68(19):7750–7759, 2008.
4.

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)
5.

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.
6.

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.
7.

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.
8.

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
9.

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
10.

Shalini J, Chakraborty G and Kundu GC: The Crucial Role of cyclooxygenase-2 in osteopontin induced PKCα/c-Src/IKKα/β dependent prostate tumor progression and angiogenesis. Cancer Res 66 (13), 6638-6648, 2006
11.

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.
12.

Rangaswami H, Bulbule A and Kundu GC: Osteopontin: role in cell signaling and cancer progression. Trends in Cell Biol. 16 (2), 79-87, 2006.
13.

Das R, Philip S, Mahabeleshwar GH, Bulbule A and Kundu GC:      Osteopontin: its role in regulation   of cell motility and nuclear factor kB-mediated urokinase type plasminogen activator expression. IUBMB Life 57 (6), 441-447, 2005.
14.

Rangaswami H, Bulbule A and Kundu GC: Nuclear factor inducing    kinase plays crucial role in osteopontin-induced MAPK/IKK dependent nuclear factor kB-mediated promatrix metalloproteinase-9 activation. J. Biol. Chem. 279 (37), 38921-38935, 2004.  

15.

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.
16.

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.

17.

Philip S, Bulbule A and Kundu GC: Matrix metalloproteinase-2: mechanism and regulation of NF-kB-mediated activation and its role in cell motility and ECM-invasion. Glycoconjugate J. 21, 429-441, 2004

18.

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.
19.

Mahabeleshwar GH and Kundu GC: Tyrosine kinase, p56lck regulates cell motility and NF-kB mediated secretion of urokinase type plasminogen activator through tyrosine phosphorylation of IkBa following hypoxia/reoxygenation. J. Biol. Chem. 278 (52), 52598-52612, 2003.
20.

Das R, Mahabeleshwar GH and Kundu GC: Osteopontin stimulates cell motility and NF-kB 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
21.

Takada Y, Mukhopadhyay A, Kundu GC, Mahabeleshwar GH, Singh S, and Aggarwal BB: Hydrogen peroxide activates NF-kB through tyrosine phosphorylation of IkBa and serine phosphorylation of p65: Evidence for the involvement of IkBa kinase and Syk protein tyrosine kinase. J. Biol. Chem. 278 (26), 24233-24241, 2003
22.

Philip S and Kundu GC: Osteopontin induces NF-kappa B mediated promatrix metalloproteinase-2 activation through IKK/IkBa signaling pathways and curcumin (diferulolylmethane) down regulates these pathways. J. Biol. Chem. 278 (16), 14487-14497, 2003.

23.

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.

24.

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.
25.

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.  

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Patents granted

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

                                                                                                           

Past Students

Dr. Subha Philip
Dr. Ganapati H. Mahabeleshwar
Dr. Riku Das
Dr. Hema Rangaswami
Dr. Goutam Chakraborty
Dr. Shalini Jain

                                                                                   

Present Sudents

Ms. Reeti Behera
Mr. Mansoor Ahmed
Ms. Priyanka Sharma
Mr. Vinit Kumar
Ms. Rajinder Kaur
Ms. Remya Raja
Ms. Smita Kale
Mr. Santosh Kumar
Ms. Rosalin Mishra
Ms. Madhvi Mandhania
Ms. Dhanashri Thorat

Ms. Anuradha Bulbule (Technician-C)

 

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Member of Scientific Society/Journal Editorial Board

1. Member of New York Academy of Sciences, USA (2000-2001)
2. Life member of Indian Society of Cell Biology
3. Member of Molecular Immunology Forum
4. Fellow of the National Academy of Sciences, India
5. Member of Guha Research Conference (GRC)
6. Fellow of Maharashtra Academy of Sciences
7. Fellow of the Indian Academy of Sciences  
8. Member of American Society for Biochemistry and Molecular Biology, USA  
9. Editorial Board Member of Current Molecular Medicine, USA
10. Editorial Board Member of Molecular Medicine Reports, Greece
11. Served as reviewer in Nature, Nature Reviews Cancer, JNCI, MCB, JBC, Cancer Research, Clinical Can Res,  Expt. Cell Res., Gastroenterology, FASEB J,  Eur. J. Cancer, Oncogene, Carcinogenesis, Life Sciences, BMC Cancer, JCMM, Lab. Invest., Intl. J. Cancer, Cancer Lett, PLOS One, BBRC and grant proposals from Wellcome Trust UK, Cancer Research UK, MRC UK and Health Research Board (HRB), Ireland.  

                                                                                                      

Awards & Achievement

1. Prof. R.C. Shah Memorial Lecture Award, The Indian Science Congress Association, 2004.
2. National Bioscience Award for career development, Department of Biotechnology, New Delhi, 2003.
3. Shanti Swarup Bhatnagar Prize in Biological Sciences, Council of Scientific and Industrial Research (CSIR), New Delhi, Govt. of India, 2004.

 

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