Source: http://microbiology.med.uky.edu/users/vmrang01
Timestamp: 2019-04-25 06:58:00+00:00

Document:
Dr. Vivek M. Rangnekar’s laboratory studies the molecular cross-talk between oncogenes and tumor suppressor genes, in an effort to tilt the balance in favor of tumor suppressor function. The strategy is to utilize the inherent strengths of the tumor against itself, to specifically target cell survival mechanisms that are common to diverse cancers, while leaving the normal host cells unharmed. The multi-faceted tumor suppressor protein Par-4/PAWR, originally identified by Dr. Rangnekar in 1993, serves as a paradigm for such studies. Interestingly, up-regulation of Par-4 protein induces apoptotic death specifically in cancer cells, and its absence leads to tumor growth. Par-4 induces apoptosis intracellularly acting in the cytoplasm or nucleus, or extracellularly via its cell surface receptor GRP78. Dr. Rangnekar’s team is now studying novel Par-4 secretagogues that can cause elevated secretion of Par-4 for inhibition of primary and metastatic tumors.
NIH/NCI R01 CA187273 (PI: Rangnekar VM) 07/01/15-06/30/20 "Suppression of Prostate Tumor Growth and Metastasis by Inhibition of Vimentin"
NIH/NCI T32 CA165990 (Multi-PI: Rangnekar, VM and Evers, BM) 04/01/13-03/31/21 “Interdisciplinary Research Training in Cancer Biology” Goals: This project is to train pre-doctoral students and post-doctoral scholars in cancer biology.
NIH/NCI P30 CA177558 (PI: Evers, BM) 07/01/13-06/30/18) “University of Kentucky Markey Cancer Center – Cancer Center Support Grant” Role: Program Co-leader, Cancer Cell Biology and Signaling.
NIH/NCI R21 CA179283 (PI: Rangnekar, VM) 04/01/14-03/31/18 "Regulation of Par-4 Secretion in Normal Cells for Paracrine Action in Cancer Cells"
Programmed Cell Death: Cellular and Molecular Mechanisms (volume 1) and Role in Disease, Pathogenesis &amp; Prevention (volume 2). (Elsevier Science, Inc., NY). Editors: M. P. Mattson, S. Estus, and V. M. Rangnekar. January 2001.
A. Goswami, R. Burikhanov, A. de Thonel, N. Fujita, M. Goswami, Y. Zhao, J. E. Eriksson, T. Tsuruo, and V. M. Rangnekar (2005) Binding and phosphorylation of Par-4 by Akt is essential for cancer cell survival. Molecular Cell 20: 33–44.
A. Goswami, P. Ranganathan and V. M. Rangnekar (2006) The PI3K-Akt1-Par-4 Axis: A Cancer-Selective Therapeutic Target. Cancer Res. 66, 2889-2892.
Y. Zhao, R. Burikhanov, S. Qiu, S. M. Lele, C. D. Jennings, S. Bondada, B. Spear, and V. M. Rangnekar (2007) Cancer resistance in transgenic mice expressing the SAC module of Par-4. Cancer Res. 67: 9276-9285.
K. M. Vasudevan, R. Burikhanov, A. Goswami, and V. M. Rangnekar (2007) Suppression of PTEN expression is essential for antiapoptosis and cellular transformation by oncogenic Ras. Cancer Res. 67: 10343-10350.
A. Goswami, S. Qiu, T. S. Dexheimer, P. Ranganathan, R. Burikhanov, Y. Pommier and V. M. Rangnekar. (2008) Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation activity. Cancer Res. 68: 6190-6198.
R. Burikhanov, Y. Zhao, A. Goswami, S. Qiu, S. R. Schwarze, and V. M. Rangnekar. (2009) The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis. Cell 138: 377-388.
T. Bhattarai and V. M. Rangnekar (2010) Cancer-selective apoptotic effects of extracellular and intracellular Par-4. Oncogene 29: 3873–3880.
Y. Zhao, R. Burikhanov, J. Brandon, S. Qiu, B. J. Shelton, B. Spear, S. Bondada, S. Bryson and V. M. Rangnekar (2011) Systemic Par-4 inhibits metastatic tumor growth. Cancer Biol Ther. 12: 152-157.
G.W.Warren, M. Romano, M.R. Kudrimoti, M.E. Randall, R.M. McGarry, A.K. Singh, and V.M. Rangnekar. (2012) Nicotinic modulation of therapeutic response in vitro and in vivo. Int. J. Cancer 131:2519-2527.
R. Burikhanov, T. Shresta-Bhattarai, S. Qiu, N. Shukla, N. Hebbar, S. Lele, C. Horbinski, and V. M. Rangnekar (2013) Novel mechanism of apoptosis resistance in cancer mediated by extracellular PAR-4. Cancer Res. 73:1011-1019.
T. Shrestha-Bhattarai, N. Hebbar, and V.M. Rangnekar (2013) Par(-4)oxysm in Breast Cancer. Cancer Cell 24(1):3-5.
R. Burikhanov, T. Shrestha-Bhattarai, N. Hebbar, S. Qiu, Y. Zhao, G. Zambetti, and V. M. Rangnekar (2014) Paracrine apoptotic effect of p53 mediated by tumor suppressor Par-4. Cell Reports 6:271–277.
Ravshan Burikhanov, Vitaliy M Sviripa, Nikhil Hebbar, Wen Zhang, W John Layton, Adel Hamza, Chang-Guo Zhan, David S Watt, Chunming Liu and Vivek M Rangnekar (2014) Arylquins target vimentin to trigger Par-4 secretion for tumor cell apoptosis. Nature Chem Biol. 10(11): 924–926.
Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar (2017) Chloroquine-inducible Par-4 secretion Is essential for tumor cell apoptosis and inhibition of metastasis. Cell Reports 18 (2): 508-519.
Hebbar N, Burikhanov R, Shukla Ni, Qiu S, Zhao Y, Elenitoba-Johnson KSJ, and Rangnekar VM. (2017) A naturally generated decoy of the prostate apoptosis response-4 protein overcomes therapy resistance in tumors. Cancer Res 77:4039-4050.
Patent # 7,786,275, on August, 31 2010, to Vivek M. Rangnekar (radiation medicine) for "Identification of a unique core domain of Par-4 sufficient for selective apoptosis induction in cancer cells."
Patent Application No. PCT/US2014/066796: Arylquinoline and arylbenzopyran compounds and use of such to treat cancer.

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