Personal Statement
I have been studying cellular pathways, factors and mechanism involved in maintenance of genomic integrity since last 12 years and acquired training, expertise and knowledge required to successfully pursue the proposed study.
During my doctoral studies I worked with Dr. Shelley L. Lusetti at New Mexico State University (NMSU) and received training in protein biochemistry, enzymology and molecular biology while focusing on the delineating the role of bacterial recombinational protein RecN in DNA double-strand break (DSB) repair via homologous recombination (HR). During my postdoctoral research, I worked with Dr. David A. Boothman at the University of Texas Southwestern Medical Center (UTSouthwestern), and received broad training in genetics, cell and molecular biology, proteomics, genomics, bioinformatics and cancer biology while identifying and characterizing novel human proteins including Kub5-Hera, XRN2, and p15RS that are involved in preserving genomic integrity through avoiding R-loop formation and ensuring efficient non-homologous end joining (NHEJ).
I have been closely involved in delineating the phenotype arise after XRN2, Kub5-Hera and p15RS loss that include increased R-loop formation, elevated DSB formation, sensitivity to a variety of DNA damaging agents, defects in NHEJ-mediated DSB repair pathways, and sensitivity to PARP inhibition. I was also working on NAD(P)H:quinone oxidoreductase 1 (NQO1)-dependent redox-cycling of quinones as an anti-cancer targeted therapy against lung (NSCLC), pancreas (PDAC), and breast cancer as a single agent or in combination with PARP inhibitors. These cancers show elevated NQO1 levels compared to surrounding normal tissue and are prone to undergo apoptosis or programmed necrosis in response to NQO1-dependent redox-cycling of quinones.
During my postdoctoral training, I worked as a co-investigator on several NIH funded grants (PI: Boothman) and laid the foundation for my current research project by identifying poly(ADPribose) polymerase 1 (PARP1) as a novel binding partner of XRN2 and investigating the significance of this interaction in the context of preserving genomic integrity.
I established my own laboratory in fall 2016 here at New Mexico Tech and maintained a strong commitment toward understanding how the interplay between XRN2 and PARP1 might regulate R-loop resolution to preserve genomic stability and received NIH R15 grant in 2018. The current NIH R15 GM128071-01A1 grant proposal capitalizes on my previous and on going work. The mission of my laboratory is to understand the molecular mechanism that cells employ to preserve genomic integrity and identify avenues to exploit differential cellular stress responses in cancer versus normal cells.
Currently, my laboratory is focused on three main projects: i) characterizing interactome of XRN2 and seeking biological significance of novel interaction potentially important for avoiding genomic instability, ii) NQO1- dependent redox-cycling of quinones and quinone-mimics as an anti-cancer targeted therapy, and iii) Kub5- Hera as a determinant of DNA topoisomerase 1 (TOP1) function in R-loop resolution and preserving genomic integrity.