Assistant Professor, Biochemistry and Molecular Genetics
- MSc, Life Sciences, Jawaharlal Nehru University
- PhD, Computational Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD)
- Postdoc, Genomics, University of Virginia
1340 Jefferson Park Ave
1312A Pinn Hall
Charlottesville, VA 22908
Bioinformatics and Genomics
Bioinformatics Core Director; Biogenesis and Function of Transfer RNA-Related Fragments (tRFs); Study of extrachromosomal circular DNA (eccDNA) or double minutes to understand Tumor heterogeneity
Bioinformatics Core: As a Bioinformatics Core Director at the University of Virginia, I have been privileged to work with great colleagues and have the opportunity to make contributions to biomedical research and perform integrative analysis of multiple functional genomics data sets. I have been leading the University of Bioinformatics core since 2019. This has given me additional opportunity to collaborate with a battery of scientists across grounds whose research interests are varied and span different areas like the microbiome, metagenomics, metabolomics, proteomics, transcriptomics, eQTL analysis, single nucleotide variation, structure variation of the genome, single-cell genomics to understand the heterogeneity between the cells, etc. I have been supporting colleagues and collaborators across the university with bioinformatics analysis, statistical analysis, data interpretation and grant writing (as a Co-I) to fulfill aims that need bioinformatics and statistical expertise.
My laboratory used computational methods to make novel biological discoveries about the regulation of gene expression in cancers from genomic and transcriptomic data generated by consortia like The Cancer Genome Atlas (TCGA), Encyclopedia of DNA elements (ENCODE), etc. An unbiased approach to analyzing high-throughput small RNA sequencing data resulted in the discovery of a new class of small RNAs called transfer RNA fragments (tRFs). Ongoing projects in the lab examine how tRFs impact on gene expression and cancer.
I was one of the first authors from the group (my postdoc lab) that used first paired-end high throughput sequencing methods to identify circular DNA at base-pair resolution. I developed one of the first computational methods (Circle_finder available at https://github.com/pk7zuva/Circle_finder), which can identify circular DNA from any type of paired-end high throughput sequencing data. The genome-wide abundance of eccDNAs and their functional importance are not very well understood. These eccDNA sequences are a few hundred kbs to a few megabases in size. My interest is in longer eccDNA as they are expected to harbor full-length gene sequences. I have been working on circular DNA for over a decade.
TRFs are a heterogeneous class of small RNAs, with the most abundant ones classified into groups: tRF-5 arising from 5 end of mature tRNA, tRF-3 from 3 end of mature tRNA, tRF-1 arising from 3 end of primary tRNA and tiRs (tRNA halves) that are generated by cleavage in the anticodon loop. While tRF1 is generated during tRNA maturation by RNase Z, not much is known of the factors responsible for the biogenesis of other tRFs viz. tRF5s, tRF3s and tiRs. Also, the biological function of a vast majority of the tRFs is unknown. Our analysis of the Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) of Argonaute (AGO) protein and cross-linking ligation and sequencing of hybrids (CLASH) data suggest that tRFs bind to Argonaute proteins (AGO) and base pair with target genes in a manner similar to miRNA. . By comparison with microRNAs, another family of small RNAs that bind to AGO proteins and base-pair with target genes, we hypothesize that this will function as tumor suppressors or as oncogenes and be involved in cellular and pathological processes like apoptosis and neurodegeneration. We are also interested to understand the biogenesis and function of this, specifically, its gene-regulatory role in cancer. Finally to help achieve this goal and facilitate research on this we created and maintain a publicly available database of tRFs called tRFdb (http://genome.bioch.virginia.edu/trfdb/index.php ) that lists the sequences of abundant tRFs in different species and potential target genes.