Position Title

Associate Professor/ Director of IM PhD/MS Program

Biography

Raghavendar Thipparthi, PhD., is Associate Professor in the Department of Biochemistry, Microbiology and Immunology. Dr. Thipparthi received his PhD from the University of Hyderabad, Hyderabad, India (1989). He was a visiting scientist (1989) at the Oak Ridge National Laboratory, Tennessee; Post-graduate researcher (1990 - 93), and Assistant Research Scientist (1994 - 2000) in Dr. Flossie Wong-Staal's lab, Department of Medicine, University of California, San Diego, CA. He joined the faculty in Immunology and Microbiology in November 2000.

Education

 PhD: School of Life Sciences (Dept of Biochemistry), University of Hyderabad, India

Graduate

Accepting new MS students in 2024: Yes (IM)
Accepting new PhD students in 2024: No

Office Location

7213 Scott Hall

Research

Post-transcriptional regulation of human immunodeficiency virus (HIV) gene expression

Research Focus

The human immunodeficiency virus -1 (HIV-1) differentially controls viral protein expression at the level of splicing as well as the nuclear export of incompletely spliced viral RNAs. The HIV-1 Rev protein, which shuttles between the nucleus and cytoplasm, facilitates the nuclear export of unspliced mRNAs containing the Rev response element (RRE). This process, mediated by the Rev/RRE, interfaces with cellular components involved in the post-transcriptional gene regulation. Several cellular proteins that bind Rev and/or RRE have been identified, which either positively or negatively modulate Rev function. However, no cellular counterpart of Rev has been reported. We identified that a cellular protein, Sam68, can functionally substitute as well as synergize with Rev in RRE-mediated gene expression and virus production. Furthermore, we demonstrated that Sam68 is absolutely required for Rev function and HIV-1 production. The mechanism by which Sam68 enhances HIV-1 production is under investigation.

Another area of our lab focus is to understand the role of Rev in viral latency in astrocytes. Astrocytes serve as reservoirs and HIV preferentially establishes latency in these cells, partly due to mis-localization of Rev (cytoplasm) in these cells and contributes to functional block. Our hypothesis is that astrocytes express cytoplasmic protein(s) which interfere with the nuclear uptake of Rev, thus blocking the Rev function. One such protein is Hsp22, expressed at high levels in the cytoplasm of astrocytes. Currently, the role of Hsp22 in the Rev function and HIV-1 production in astrocytes is under investigation.

Publications

• Modem S, Dicarlo SE, Reddy TR. Fresh Garlic Extract Induces Growth Arrest and Morphological Differentiation of MCF7 Breast Cancer Cells. Genes Cancer. 3:177-86. 2012. Medline
• Modem S, Chinnakannu K, Bai U, Reddy GP, Reddy TR. Hsp22 (HspB8/H11) knockdown induces Sam68 expression and stimulates proliferation of glioblastoma cells. J Cell Physiol. 226:2747-51. 2011. Medline
• Suhasini M, Reddy TR. Cellular proteins and HIV-1 Rev function. Curr HIV Res. 7:91-100. 2009 Medline
• Modem S, Reddy TR. An anti-apoptotic protein, Hax-1, inhibits the HIV-1 rev function by altering its sub-cellular localization. J Cell Physiol. 2008 214:14-9. 2008. Medline
• Bagchi M, Besser D, Reddy TR, Skoff R, Maisel H. Effect of thermal stress on early and late passaged mouse lens epithelial cells. J Cell Biochem. 102:1036-42. 2007 Medline
• Badri KR, Modem S, Gerard HC, Khan I, Bagchi M, Hudson AP, Reddy TR. Regulation of Sam68 activity by small heat shock protein 22. J Cell Biochem. 99:1353-62. 2006. Medline
• Singh K.P., Gerard H.C., Hudson A.P., Reddy T.R., Boros D.L. Retroviral Foxp3 gene transfer ameliorates liver granuloma pathology in Schistosoma mansoni infected mice. Immunology, 114:410-417, 2005. Medline
• Modem S., Badri K.R., Holland T.C., Reddy T.R. Sam68 is absolutely required for Rev function and HIV-1 production. Nucleic Acids Res., 33:873-879, 2005. Medline
• Yang J.P., Reddy T.R., Truong K.T., Suhasini M., Wong-Staal F. Functional interaction of Sam68 and heterogeneous nuclear ribonucleoprotein K. Oncogene, 21:7187-7194, 2002. Medline
• Xu W., Zhang Y., Yeh L.Y., Ruprecht C.R., Wong-Staal F., McFadden B.A., Reddy T.R., Ruprecht R.M. One-step, highly efficient site-directed mutagenesis by toxic protein selection. Biotechniques, 32:1266-1268, 1270, 2002. Medline
• Reddy T.R., Suhasini M., Xu W., Yeh L.Y., Yang J.P., Wu J., Artzt K., Wong-Staal F. A role for KH domain proteins (Sam68-like mammalian proteins and quaking proteins) in the post-transcriptional regulation of HIV replication. J. Biol. Chem., 277:5778-5784, 2002. Medline
• Yang, J-P., Tang, H., Reddy, T. R., and Wong-Staal, F. (2001). Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type-D retroviruses. J. Biol. Chem., 276:30694-30700, 2001. Medline
• Reddy, T. R., Xu, W., and Wong-Staal. F. (2000). General effect of Sam68 on Rev/Rex regulated expression of complex retroviruses. Oncogene 19:4071-4074. Medline
• Reddy, T. R., Tang, H., Xu, W., and Wong-Staal. F. (2000). Sam68, RNA helicase A and Tap co-operate in the post-transcriptional regulation of retroviral mRNA. Oncogene 19:3570-3575. Medline
• Reddy, T. R. (2000). A single point mutation in the nuclear localization signal (NLS) of Sam68 blocks the Rev/RRE-mediated post-transcriptional regulation of HIV-1. Oncogene 19:3110-3114. Medline
• Westberg, C., Yang, J-P., Tang, H., Reddy, T. R., and Wong-Staal, F. (2000). A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element. J. Biol. Chem. 275:21396-21401. Medline

 

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