M.S. Medical Biology, CW Post campus Long Island University
PhD. Biomedical Sciences, University of Maine, 2018
Sathyabhama University, Chennai,Tamil Nadu,India. – Bachelor of Technology (2002-2006) Biotechnolgy
Institute of Genetics and Hospital for Genetic Disorders, Hyderabad, A.P,India – Research Assistant (2006-2007)
Long Island University, C.W.Post Campus, Brookville,NY.- Master of Science (2007-2009) Medical Biology Major in Immunology
The Rockefeller University, New York – Research Assistant (2009-2012)- Dr.Nathaniel Heintz Lab.
Jackson Laboratory, The University of Maine – Pre-Doctoral Student (2012-Present) -Dr.Robert E Braun Lab.
First Year Lab Rotations: Dr. Carol Kim (University of Maine), Dr.Susan Ackerman (Jackson Laboratory)
Spermatogenesis is a process during which haploid spermatids are produced from diploid spermatogonia after mitotic proliferation and meiosis. This process is then followed by spermiogenesis; during which round spermatids differentiate into spermatozoa. Post-transcriptional regulation of gene expression is a major form of gene regulation in gametogenesis and it involves degradation of mRNA transcripts or translation blockage. Both processes rely upon either specific RNA-protein interactions or formation of a double stranded RNA. My research is aimed towards identifying the role of a double stranded RNA binding protein (dsRBP) TARBP2 in post-transcriptional regulation of gene expression during the process of gametogenesis
MicroRNAs (miRNAs) mediated post-transcriptional regulation of gene expression is required at various stages of spermatogenesis to ensure the production of fully- differentiated spermatozoa. miRNAs are ~22 nucleotide non-coding RNAs that function as post-transcriptional regulators by modulating mRNA translation and stability. In the canonical miRNA biogenesis pathway, the RNase III enzyme DICER cleaves the ~70nt pre-miRNA “hairpin”, to produce a duplex dsRNA that is loaded into the RNAi effector mechanism, the RNA induced silencing complex (RISC). DICER binds two dsRBP co-factors, TARBP2 and PRKRA, which modulate pre-miRNA “dicing” kinetics, cleavage site selection and loading of the miRNA duplex into the RISC. Mutations in either of these dsRBPs lead to the disruption of miRNA processing abilities of DICER and can impact mammalian spermatogenesis and cancer.
TARBP2 is highly expressed in mouse testis where it is predominantly expressed in germ cells as previously shown by our lab. Tarbp2 mutants are sterile and have defects in translational activation of Prm1 mRNA, which is under temporal translational regulation during spermiogenesis. It is unknown if the defective translational activation of the Prm1 mRNA is mediated through the action of TARBP2 as a cofactor of DICER, or whether the effect is independent of DICER and miRNAs. However the discordance between the phenotype of Tarbp2 mutants and a germ cell specific knock out of Dicer1, suggest that TARBP2 have a novel function in post-transcriptional regulation apart from miRNA biogenesis and I propose to test the post-transcription regulation of gene expression by TARBP2 independent of miRNAs during spermatogenesis. Using a wild type mouse testis, immunoprecipitation of RNA-Protein complex with antibody against TARBP2 combined with high throughput sequencing will reveal the transcripts that bind to TARBP2. Whole RNA sequencing data combined with polysomal profile analysis comparing Tarbp2+/+and Tarbp2-/- testis will reveal whether the post-transcriptional gene regulation mediated by TARBP2 is through degradation of mRNA transcripts or by blocking translation. Successful completion of these studies will provide new insights into the post-transcription regulation of gene expression by TARBP2 and will therefore present an appealing target for therapeutic intervention of male sterility and cancer.
- Mikulak, J., Teichberg, S., Arora, S., Kumar, D., Yadav, A., Salhan, D., Pullagura, S., Mathieson, P.M., Saleem, M.A., Singhal, P.C., 2010. DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes. Am.J. Physiol. Ren. Physiol. 299 (3), F664–F673. Read Abstract