Department of Veterinary Pathobiology

Bimal Ray
Professor

  • PhD, Calcutta University

Building Address: 124 Connaway Hall
Phone Number: 573-882-4461
Email: RayB@missouri.edu

Teaching Responsibilities: Molecular Basis of Health and Disease

Research Emphasis: My laboratory is interested in studying molecular basis of inflammation-induced diseases and current research focuses on arthritis and cancer. Our goal is to discern new information on the molecular events that are responsible for the pathogenesis of these diseases and to use this knowledge to develop new approaches for effective treatment. Abnormal gene expression, which plays a critical role in the pathogenesis of these diseases, is a major target of our investigation. Activation of transcription factors by mechanisms involving signal transduction and epigenetic modulation of chromatin structure that influences assembly of regulatory proteins at the chromosomal genes are some of the crucial molecular events we have been investigating. Our studies have revealed the identity of a novel transcription factor called SAF, serum amyloid A activating factor. We have extensively studied several structural features of this protein which belongs to a family of at least four members that are derived from a single gene by alternative splicing mechanism. Activation of SAF by different signaling pathways involving MAP kinase, PKA, PKC and mTOR provides an opportunity to control its activity with different pharmacological agents. Abnormal activity of several transcription factors plays an important role in the angiogenesis in cancer and therefore, we investigate this event to develop novel control measures against cancer growth and metastasis. We also explore gene silencing approach with siRNA/shRNA technology to control abnormal gene activities associated with arthritis and cancer.

Teaching: Molecular Biology

Selected Publications:

Ray, A., Alalem, M., and Ray, B. K. (2013) Loss of epigenetic Kruppel-like factor 4-histone deacetylase –mediated transcriptional suppression is crucial in increasing vascular endothelial growth factor expression in breast cancer.  J. Biol. Chem. 288: 27232-27242.

Ray, B.K., Dhar, S., Henry, C., Rich, A. and  Ray, A. (2013) Epigenetic regulation by Z-DNA silencer function controls cancer-associated ADAM-12 expression in breast cancer:  crosstalk between MeCP2 and NF1 transcription factor family. Cancer Res. 73: 736-744.

Ray, B.K., Dhar, S., Shakya, A. and  Ray, A. (2011)  Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression. Proc. Natl. Acad. Sci. U.S.A.  108: 103-108.

Ray, A., Dhar, S., and  Ray, B. K. (2011) Control of VEGF expression in triple negative breast carcinoma cells by suppression of SAF-1 transcription factor activity.  Mol. Cancer Res. 9: 1030-1041.

Ray, B.K., Dhar, S., and  Ray, A. (2010) TGF-b1 mediated activation of  NF-kB contributes to enhanced ADAM-12 expression in mammary carcinoma cells. Mol. Cancer Res. 8: 126-1-1270.

Kumar, D., Ray, A., and Ray, B.K. (2009) Transcriptional synergy mediated by SAF-1 and AP-1: critical role   of N-terminal polyalanine and two zinc finger domains of SAF-1.  J. Biol. Chem. 284: 1853-1862.

Ray, A., Dhar, S., Shakya, A., Ray, P., Okada, Y. and  Ray, B.K. (2009) SAF-3, a novel variant of the SAF-1/MAZ/Pur-1 family, is expressed during inflammation.  FEBS. J. 276: 4276-4286.

Ray, A. and Ray, B.K. (2008) An inflammation-responsive transcription factor in the pathophysiology of osteoarthritis. Biorheology 45: 399-409.

Ray, B. K.., Shakya, A., and Ray, A. (2007) VEGF expression in arthritic joint is regulated by SAF-1 transcription factor.  J. Immunol. , 178: 1774-1782.

Ray, A., Shakya, A., Kumar, D., Benson, M.D., and Ray, B.K. (2006) Inflammation-responsive transcription factor SAF-1 activity is linked to the development of AA amyloidosis. J. Immunol 177: 2601-2609

Ray, A.,  Bal, B.S., and Ray, B.K. (2005) Transcriptional induction of MMP-9 in the chondrocyte and synoviocyte cells is regulated via a novel mechanism: evidence for functional cooperation between SAF-1 and AP-1.  J. Immunol. 175: 4039-4048.

Ray, A.,  Shakya, A., Kumar, D. and Ray, B.K. (2004) Over-expression of SAF-1 inhibits cell proliferation by the induction of cyclin-dependent protein kinase inhibitor p21 expression. J. Immunol. 172: 5006-5015.

Ray, A., Kumar, D., Shakya, A., Brown, C.R. Cook, J.L. and Ray, B.K. (2004) SAF-1 transgenic mice are prone to develop severe form of inflammation-induced arthritis. J. Immunol. 173: 4684-4691.

Ray, A., Kumar, D., Ray, P., and Ray, B.K. (2004) Transcriptional activity of SAF-1 is regulated by distinct functional modules. J. Biol. Chem. 279: 54637-54646.

Ray, B.K., Shakya, A., Turk, J.R., Apte, S.S., and Ray, A. (2004) Induction of the MMP-14 Gene in Macrophages of the Atherosclerotic Plaque:  Role of SAF-1 in the Induction Process. Circulation Res. 95: 1082-1090.

Ray, A., Ray, P., Guthrie, N., Shakya, A., Kumar, D. and Ray, B.K. (2003) Protein kinase A signaling pathway regulates transcriptional activity of SAF-1 by unmasking its DNA-binding domains. J. Biol. Chem. 278: 22586-22595

Ray, A., Kuroki, K., Cook, J.L., Bal, B.S., Kenter, K., Aust, G., and Ray, B.K. (2003) Induction of matrix metalloproteinases-1 gene expression is regulated by inflammation-responsive transcription factor SAF-1 in osteoarthritis .  Arthritis & Rheumatism  48: 134-145

Ray, A., Yu, G.-Y and Ray, B.K. (2002) Cytokine responsive induction of SAF-1 activity is mediated by a MAP kinase signaling pathway.  Mol. Cell. Biol. 22: 1027-1035.

Ray, B.K., Murphy, R., Ray, P., and Ray, A. (2002) SAF-2, a splice variant of SAF-1 acts as a negative regulator of transcription.  J. Biol. Chem.  277: 46822-46830

 

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