Channa Reddy

BRIEF RESUME OF C. CHANNA REDDY                C. Channa Reddy obtained his PhD in Biochemistry from Indian Institute of Science, Bangalore, in 1975 and Joined as a Post-Doc in the department of Chemistry at Penn State University. He is currently Distinguished Professor Emeritus at Penn State. He was the Chairman of the Department of Veterinary and Biomedical Sciences from 1994 to 2006 at Penn State. Also, he served as the Director of the Huck Institutes of the Life Sciences from 2002 to 2006 at Penn State. He was an awardee of “Research Career Development Award” (RCDA) from National Institute of Health (1983-1988). He was Elected Fellow of the American Association for the Advancement of Science in1992. During his 45-year tenure at Penn State university, he served on 3 NIH study sections and a member of the Editorial Board for a number Scientific Journals.  Recently, he has taken retirement and started a Biotech Company “INDUS Gene Expressions Ltd” near Bangalore. The Company’s focus is contract manufacturing of Monoclonal Antibody Therapeutics.The Major thrust of his research during his Tenure at Penn State has been in Molecular Aspects of Biological Oxidation Reactions: More specifically, the Redox-Based Regulation of Gene Expression. Of particular importance is the oxidative stress induced over-expression of cyclooxygenase (COX)-2 that is characteristic of inadequate selenium (Se) nutrition. In macrophages, COX-2 is induced by not only redox status, but by inflammatory stimuli as well. In contrast, the expression of COX-1 is constitutive and not affected by redox status. Together, these enzymes regulate the metabolism of arachidonic acid (20:4) in macrophages to produce important lipid mediators like prostaglandins (PGs), thromboxanes, and prostacyclins. Interestingly, Se-supplementation of activated macrophages causes a dramatic shift in 20:4 metabolism from a pro-inflammatory PGE2 to an anti-inflammatory PG, 15-deoxy-12,14-PGJ2 (15d-PGJ2), which down-regulates the pro-inflammatory cytokine expression. Thus, the regulation of 20:4 metabolism leading to the augmented production of 15d-PGJ2 could represent one of the underlying mechanisms of anti-inflammatory and anti-carcinogenic properties of Se. Most importantly, 15d-PGJ2 has its own unique spectrum of biological effects, including inhibition of IB kinase activity and macrophage-derived cytokine production, which may have significant therapeutic implications. The transcription factors, nuclear factor-kappa B (NF-B) and peroxisome proliferator activated receptor (PPAR)-γ, which influence pro-inflammatory and anti-inflammatory functions, respectively, are differentially modulated by 15d-PGJ2. Thus, defining the mechanism underlying the selective formation of 15d-PGJ2 in Se-supplemented macrophages and its role in the control of expression of pro-inflammatory genes is one of the major goals of his research program. The specific hypothesis is that Se supplementation selectively modulates several enzymes associated with 20:4 metabolism via the COX pathway, thereby influencing the preferential formation of an anti-inflammatory PG (15d- PGJ2), which attenuates the expression of pro-inflammatory genes through modulation of transcriptional factors, NF-B and PPARγ. An additional complementary hypothesis is that the expression of microsomal glutathione transferase A1 (MGSTA1) is up-regulated during Se deficiency, which is partially responsible for the metabolic transformation of 15d-PGJ2 into an inactive form.