Sreenivasa R. Chinni
Sreenivasa R. Chinni, Ph.D.
9200 Scott Hall
540 E. Canfield
Detroit, MI 48201
- Characterizing cellular and molecular pathological events contributing to prostate cancer progression.
- Chemokine and chemokine receptor axis signaling in lipid raft membrane microdomains of prostate cancer cells.
- Identifying ERG gene transcription targets in prostate cancer cells.
The research focus of my laboratory is to understand the molecular mechanism of prostate cancer metastasis. Currently, we are studying the role of chemokines and chemokine receptors in tumor cell invasion and metastasis using in vitro and in vivo preclinical models of metastasis. Chemokine pathways have been shown to play a key role in primary tumor progression and site specific metastasis. We recently identified that chemokine receptor CXCR4 highly localizes to lipid rich membrane microdomains, activate members of growth factor family receptors and down stream signaling pathways. In tumor cells this transactivation pathway further contributes to intraosseous tumor growth of prostate cancer cells in addition to bone metastasis. Our current studies are directed towards characterizing the molecular intermediates regulating the CXCR4 transactivation of growth factor family receptors in prostate cancer cells. Other project in the lab is to define molecular targets of recently identified recurrent chromosomal alterations in prostate cancer patients. We have identified that androgen activation of common chromosomal translocations, TMPRSS2-ERG induce CXCR4 transcription, and thereby contributing to enhanced invasion and metastasis of prostate cancer cells. We are currently characterizing the functional significance of chromosomal translocations and chemokine receptor expression in prostate cancer metastasis.
Powell K, Semaan L, Conley-LaComb MK, Asangani I, Wu YM, Ginsburg KB, Williams J, Squire JA, Maddipati KR, Cher ML, Chinni SR. ERG/AKR1C3/AR Constitutes a Feed-Forward Loop for AR Signaling in Prostate Cancer Cells. Clin. Cancer Res. 21:2569-79.
Wong D, Kandagatla P, Korz W, Chinni SR. Targeting CXCR4 with CTCE-9908 inhibits prostate tumor metastasis. BMC Urol. 2014;14:12.
Chinni S, Singareddy R, Semaan L, Conley-Lacomb MK, St John J, Powell K, Iyer M, Smith D, Heilbrun LK, Shi D, Sakr W, Cher ML.Transcriptional regulation of CXCR4 in prostate tumor cells: Significance of TMPRSS2-ERG fusions. . Mol Cancer Res. 2013;11:1349-61.
Conley-Lacomb MK, Saliganan A, Kandagatla P, Chen YQ, Cher ML, Chinni SR. PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling. Mol Cancer. 2013;12:85.
St John J, Powell K, Conley-Lacomb MK, Chinni SR. TMPRSS2-ERG Fusion Gene Expression in Prostate Tumor Cells and Its Clinical and Biological Significance in Prostate Cancer Progression. J Cancer Sci Ther. 2012;4:94-101.
Cai, J., Kandagatla, P., Singareddy, R., Kropinski, A., Sheng, S., Cher, M.L., and Chinni, S.R. Androgens Induce Functional CXCR4 via ERG Factor Expression in TMPRSS2-ERG Fusion Positive Prostate Cancer Cells. Transl Onclol. 2010;3:195-203.
Education and Training
PhD (1998): University of Louisville, Louisville, Kentucky
Postdoctoral Fellowship (1998-2002): Wayne State University, Detroit, Michigan
Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling