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Search Program Faculty/Research

Pothana Saikumar, Ph.D.

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RESEARCH

Cell death is an important mechanism in the pathogenesis of many diseases as well as homeostasis in adult tissues. Dr. Pothana Saikumar's research is aimed at elucidating the biochemical and molecular mechanisms of cell death that occurs in the context of hypoxia as well as cancer chemotherapy. 

Mitochondrial outer membrane permeabilization, associated with most apoptotic stimuli, results in the release of apoptogenic proteins like Cytochrome c, Smac/DIABLO, and HtrA2/Omi from mitochondria and is regulated by both pro- and anti- apoptotic members of the Bcl-2 family of proteins. They have previously shown that hypoxia induces the translocation of Bax, a death promoting protein, from cytosol to mitochondria, followed by its oligomerization along with Bak protein in the membrane and release of cytochrome c from mitochondria to the cytosol. 

Recently, a model involving mitochondrial fragmentation has been suggested as a complementary mechanism for mitochondrial outer membrane permeabilization. 

However, their studies identified 15d-PGJ2, a product of inflammatory COX-2 during reoxygenation, inducing cell death with mitochondrial fusion preceding the death. They are currently studying the mechanisms involved in the dynamic alterations of mitochondrial shape associated with apoptosis. 

Many cancers are resistant to classical drug/radiation therapies, which induce apoptosis. In this regard, they have identified compounds that could induce nonapoptotic cell death termed as cytoplasmic vacuolation death or paraptosis in apoptosis resistant cancer cells. They reported that upregulation and processing of autophagy marker LC3 is an important event in non-autophagic cytoplasmic vacuolation death. They are further exploring the signaling mechanisms of this novel death pathway as well as of its utility in treating therapy resistant cancers. 

Molecular basis by which a tumor suppressive TGF-β signaling promotes tumor progression in advanced cancers is not known. They recently identified a TGF-β responsive gene TMEPAI (transmembrane prostate androgen-induced protein), whose expression is increased in several breast tumors. TMEPAI blocks TGF-β signaling through possible sequestration of R-Smads thus converting TGF-β from a tumor suppressor to a tumor promoter. Their current research explores the mechanisms by which TMEPAI alters TGF-β signaling and its role in tumorigenicity.

Selected Publications

Singha PK, Pandeswara S, Venkatachalam MA, Saikumar P. Manumycin A inhibits triple-negative breast cancer growth through LC3-mediated cytoplasmic vacuolation death. Cell Death Dis. 2013 Jan 17;4:e457.

Nair HB, Perla RP, Kirma NB, Krishnegowda NK, Ganapathy M, Rajhans R, Nair SS, Saikumar P, Vadlamudi RK, Tekmal RR. Estrogen receptor-beta mediates the protective effects of aromatase induction in the MMTV-Her-2/neu x aromatase double transgenic mice. Horm Cancer. 2012 Apr;3(1-2):26-36.

Lan R, Geng H, Polichnowski AJ, Singha PK, Saikumar P, McEwen DG, Griffin KA, Koesters R, Weinberg JM, Bidani AK, Kriz W, Venkatachalam MA. PTEN loss defines a TGF-β-induced tubule phenotype of failed differentiation and JNK signaling during renal fibrosis. Am J Physiol Renal Physiol. 2012 May 1;302(9):F1210-23.

Geng H, Lan R, Singha PK, Gilchrist A, Weinreb PH, Violette SM, Weinberg JM, Saikumar P, Venkatachalam MA. Lysophosphatidic acid increases proximal tubule cell secretion of profibrotic cytokines PDGF-B and CTGF through LPA2- and Gαq-mediated Rho and αvβ6 integrin-dependent activation of TGF-β. Am J Pathol. 2012 Oct;181(4):1236-49.

Lan R, Geng H, Hwang Y, Mishra P, Skloss WL, Sprague EA, Saikumar P, Venkatachalam M. A novel wounding device suitable for quantitative biochemical analysis of wound healing and regeneration of cultured epithelium. Wound Repair Regen. 2010 Mar-Apr;18(2):159-67.

Associate Professor/Research
Pathology

Education

Ph.D., Biochemistry, Indian Institute of Science, 1985

M.S., Biochemistry, Banaras Hindu University, 1979

B.S., Chemistry, Andhra University, 1976

Contact

Email: SAIKUMAR@UTHSCSA.EDU

Phone: 210-567-6597

Research Profile
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