Nucleic acid binding proteins and their involvement in cellular homeostasis and pathology.
Transcriptional and post-transcriptional gene regulatory mechanisms.
Heterogeneity of cell states and their relationship to health and disease.
Listed below are the major research projects I have completed and my role in these projects.
Department of Molecular, Cell, and Developmental Biology & Department of Biological Chemistry
Project Scientist (2024-present)
Associate Project Scientist (2022-2024)
Assistant Project Scientist (2014-2022)
Pan-cancer analysis of the expression patterns of epigenetic factors and relation to clinical outcomes
Independently Designed and Mentored Project; Related Publication: epigenetic factor
Performed a detailed comparison of tumor-to-tumor heterogeneity based on epigenetic factor expression across 24 adult and 4 pediatric cancer types.
Compared the different clinical and biological features of the patient tumor clusters determined based on epigenetic factor expression.
Worked with the mentored student in putting together an AI model for predicting clinical outcomes.
Studying the intertumoral heterogeneity in pancreatic adenocarcinoma (PDAC) based on alternative splicing events
Independently Designed and Mentored Project; Related Publication: PDAC
Performed survival analysis to show that the two patient clusters derived from intron-retention events had different clinical outcomes.
Characterized the intron retention events that were different between the two clusters and found that oncogenes exhibited lower intron retention levels in the cluster with a poorer clinical outcome.
Analyzed the role of splicing factor regulation in differential intron retention between the two clusters.
Generated a model based on protein-protein interactions between the splicing factors to explain the different clinical outcomes between the two clusters.
Role of alternative isoform usage during cell cycle exit to a quiescent state
Related Publication: APA
Analyzed RNA-seq data for proliferating and quiescent cells using transcript-based and count-based methods to get information about the differential gene expression.
Performed bioinformatics analysis to obtain differential splicing events between proliferating and quiescent conditions.
Investigated the expression of splicing and polyadenylation factors in proliferating and quiescent conditions using western blot analysis.
Confirmed alternative polyadenylation events between proliferating and quiescent conditions using quantitative RT-PCR.
Performed imaging-based migration assays to show the differential migration of proliferating and quiescent cells.
Showed the differential effects of core polyadenylation factors on alternative polyadenylation and cell migration by siRNA-mediated knockdown studies.
Probing the inter-tumor heterogeneity in triple-negative breast cancer using integrative clustering
Independently Designed and Mentored Project; Related Publication: TNBC
Devised workflows to perform single-data and integrative clustering of triple-negative breast cancer tissues from 137 patients.
Performed clinical analysis of the three clusters obtained from integrative clustering to show that one of the patient clusters has poorer clinical outcome compared to the remaining two clusters.
Compared the molecular features of the tumors from the three clusters to show the enrichment of different biological pathways in these clusters.
Role of alternative polyadenylation of RECK in cell migration and cancer
Related Publication: RECK
Validated the custom antibody for the short isoform of RECK (generated by alternative polyadenylation of RECK) using western blot analysis and immunofluorescence.
Performed western blot analysis to show the preferential expression of short RECK protein in triple-negative breast cancer cells compared to primary cells.
Demonstrated using gene knockdown methods that levels of long and short isoforms of RECK could be modulated in cancer cells by the manipulation of polyadenylation factors.
Section on Viral Gene Regulation, 2008-2014
Postdoctoral Fellow; Advisor: Dr. Judith G. Levin
Biological activities of human antiviral restriction protein APOBEC3A (A3A) and A3H
Related Publications: A3A-1 A3A-2 A3H
Investigated the determinants of the cytidine deaminase activity of A3A using highly
purified recombinant protein
Analyzed the potential of A3A to inhibit HIV-1 reverse transcription via a deaminase-independent mechanism using an in vitro assay.
Performed the initial biochemical characterization of purified A3A protein for collaborative NMR structural studies.
Interpreted the information obtained from the A3A NMR structure to design mutants for
studies of structure-function relationships.
Successfully prepared thirty catalytic and non-catalytic mutants of A3A. Investigated their enzymatic properties utilizing mammalian cell extracts in parallel with collaborative studies on inhibition of LINE-1 retrotransposition.
Probed the effect of A3A DNA mutator activity on the human genomic DNA using in vitro model systems.
Performed detailed analysis of the determinants of A3H deaminase activity using site-directed mutagenesis. Designed mutants based on bioinformatics analysis.
Role of the nucleic acid chaperone activity of HIV-1 nucleocapsid (NC) protein in reverse transcription
Developed a novel fluorescence assay to monitor the destabilization of an RNA-DNA hybrid by HIV-1 NC protein.
Measured the nucleic acid binding affinities of HIV-1 NC and Gag proteins to nucleic acids using fluorescence anisotropy to probe differences in their nucleic acid chaperone properties.
Advisor: Prof. Karin Musier-Forsyth
Postdoctoral Scholar at the Department of Chemistry, OSU; 2007-2008
Graduate Student Researcher at the Department of Chemistry, UMN; 2003-2007
Nucleic acid chaperone studies of retroviral nucleocapsid proteins using in vitro systems
Related Publications: NC-1 NC-2 NC-3 NC-4
Demonstrated the role of functional domains of HIV-1 NC using synthetic peptides representing different domains of NC and studying their nucleic acid chaperone properties.
Probed the role of different basic and aromatic residues of HIV-1 NC in its nucleic acid chaperone function using gel-based biochemical assays and fluorescence anisotropy.
Studied the nucleic acid destabilization activities of HTLV-1 NC protein by time-resolved FRET.
Developed a fluorescence quenching assay to probe the kissing-loop interactions between nucleic acids involved in the minus-strand transfer step of HIV-1 reverse transcription.