Biomedical Sciences Department
Assistant Professor
Biomedical Sciences Department
314 Henry Hall
Allendale, Michigan 49401
Phone: 616-331-2391
Fax: 616-331-2090
email: sridhars@gvsu.edu
FALL OFFICE HOURS:
Monday, Wednesday, & Friday: 11:30 a.m. - 12:30 p.m.
BMS 290 - Human Physiology
BMS 291 - Physiology Lab
B.Sc. Biochemistry, Madras University, India
M.Sc. Biochemistry, Madras University, India
Ph.D. Physiology, School of Medicine, Southern Illinois University, Carbondale, IL
Dissertation: Structural and functional analysis of the human erythrocyte glucose transporter protein
Adjunct Faculty, Biology Division, Emporia State University, Emporia, KS.
Postdoctoral Fellow, Pharmaceutical Chemistry, Higuchi Bioscience Center, University of Kansas, Lawrence, KS.
Formulation and stabilization of experimental anticancer drugs from the National Cancer Institute
Postdoctoral Fellow, Lab of Integrin Signaling & Tumorigensis, VanAndel Institute, Grand Rapids, MI.
Identifying the role of the tetraspanin protein CD82, in prostate tumor metastasis
My research interest is in the field of prostate cancer, in identifying the role of a metastatic tumor suppressor protein called CD82 (KAI1 gene). CD82 expression is lost during prostate tumor progression to metastasis. Loss of CD82 expression has also been recently shown to correlate with metastasis in a number of invasive cancers. The mechanisms by which cancers become metastatic are not clear. CD82, has been shown to associate with membrane proteins such as integrin and receptor tyrosine kinases (EGFR). During my postdoctoral work at the VanAndel Institute, I have re-expressed CD82 to normal levels in metastatic prostate tumor cell lines. Re-expression of CD82 in these tumor cells reduced invasion in vitro, and suppressed integrin- or HGF-mediated activation of the receptor tyrosine kinase c-Met. Conversely, we have also shown that suppression of CD82 expression in normal cells increases integrin mediated c-Met activation. Signaling through c-Met is required for cell migration and invasion in metastatic prostate tumor cells, which is over expressed in all metastatic prostate cancers. The exact mechanism by which CD82 regulates c-Met is my current research focus. Preliminary data suggests that CD82 may be causing either a decrease in c-Met cell surface aggregation or may be bringing in a c-Met specific phosphatase in close proximity, and thereby regulating c-Met phosphorylation/ activation. Both these mechanisms of CD82 regulation are currently under investigation. Invivo studies with mice are also under way to reconfirm the c-Met regulation observed invitro by CD82. and will be done through collaborative efforts.
1. Jumaa M., Chinnaswamy S., Svetlana S, and Stella, V.J. “Degradation of NSC-281612 (4-[bis[2-[(methylsulfonyl)oxy]ethyl]amino]-2-methyl-benzaldehyde), an experimental antineoplastic agent: The effect of pH, solvent composition, (SBE)7m-[[beta]]-CD and HP-[[beta]]-CD on stability". Journal of Pharmaceutical sciences, Vol 93, 2004.
2. Sridhar S.C, and Miranti, C.K. 2005. “Tumor Metastasis Suppressor KAI1/CD82 is a Tetraspanin” in Contemporary Cancer Research: Metastasis. Eds. C. Rinker-Schaeffer, M. Sokoloff and D. Yamada.
3. Sridhar, S.C., and Miranti, C.K. 2006. Tetraspanin KAI1/CD82 Suppresses Invasion by Inhibiting Integrin-Dependent Crosstalk with c-Met Receptor and Src Kinases. Oncogene, 25 (16).P: 2367-2378.
