T.R. Reddy, Ph.D., is Assistant Professor in the Department of Immunology and Microbiology. Dr. Reddy received his Ph.D. from the University of Hyderabad, Hyderabad, India in 1989. He was a visiting scientist (1989) at Oak Ridge National Laboratory, Tennessee; Post-graduate researcher (1990 - 93) and Assistant Research Scientist (1994 - 2000) in Dr. Wong-Staal's lab in the Department of Medicine at the University of California, San Diego. He joined the faculty in Immunology and Microbiology in November 2000.

Dr. Reddy's research interests include understanding the role of cellular proteins in the post-transcriptional regulation of human immunodeficiency virus (HIV). The Rev protein of human immunodeficiency virus (HIV) facilitates the nuclear export of unspliced or singly spliced viral mRNA. Rev has been shown to be a shuttle protein, comprised of a basic, nuclear localization sequence and a leucine-rich nuclear export sequence (NES). Rev specifically interacts with the cognate target sequence, RRE. Several cellular proteins that bind Rev and/or RRE have been identified, which either positively or negatively modulate Rev activity. However, no cellular counterpart of Rev has been reported. Recently, he has identified that a cellular protein, Sam68, can functionally substitute as well as synergize with Rev in RRE mediated gene expression and virus replication. Sam68 is a member of the KH domain family proteins. Carboxy-terminal deletion or point mutants of Sam68 inhibit the transactivation of RRE-mediated gene expression by both wild-type Sam68 and Rev.

The laboratory is currently focusing on the functional relevance of Sam68 in HIV replication: (i) to explore if Rev is functional without Sam68 in RRE-directed transactivation using (a) anti-sense Sam68 and (b) ribozyme gene expression knockout as a means to evaluate the functional relevance of Sam68 implicated in Rev-mediated transactivation; (ii) to generate an in vitro model for the enhancement of HIV-1 replication in NIH3T3 cells by Sam68; (iii) to assess the long-term protection of primary cells expressing transdominant negative mutants of Sam68 from HIV infection; (iv) to explore whether other KH family proteins also substitute for Rev function in HIV replication and (v) to decipher the Sam68-mediated RNA export pathway. A second area of interest of Dr. Reddy's laboratoty is to investigate the role of HTLV Tax in the development of neurological disorder, namely, Tropical Spastic Parapheresis (TSP). The Human T-cell Leukemia Virus (HTLV) is associated with adult T-cell leukemia and neurological disorders (TSP/HAM). The HTLV transcriptional transactivator, Tax, is known to exert its effect through protein-protein interaction with several transcription factors that activate genes in T-cell proliferation. The pathogenic mechanism in the CNS is less defined. In connection with TSP/HAM diseases, using the yeast two-hybrid system, Dr. Reddy has identified and characterized a cDNA clone corresponding to a human neuronal intermediate filament protein a-internexin. We are currently investigating: i) the in vivo assembly and co-assembly of neuronal intermediate filaments in the presence of extra-cellular and exogenously expressed Tax in neuronal cells, and ii) to identify and characterize additional cellular proteins that interact with Tax and are pertinent to TSP/HAM disease.