Aishwarya Prakash, Ph.D.
Postdoctoral Studies: University of Vermont
Ph.D.: University of Nebraska Medical Center
Various factors in our environment including ionizing radiation, chemicals found in cigarette smoke, herbicides, and known carcinogenic metals as well as normal cellular processes, generate reactive oxygen species (ROS) in a cell. ROS cause assault to DNA that leads to nuclear and mitochondrial DNA (mtDNA) damage where unrepaired damage to DNA results in mutagenesis and diseases including premature aging, neurodegenerative disorders, and various cancers. I began my independent research career as a tenure-track Assistant Professor at the University of South Alabama Mitchell Cancer Institute, Department of Biochemistry and Molecular Biology, in March 2016.
A part of my laboratory has been engaged with performing fundamental studies on the biochemistry and structural biology of base excision repair (BER) complexes involved in the repair of non-bulky lesions formed in mtDNA. We have identified components of the mitochondrial replication and transcriptional machinery that interact directly with the NEIL DNA glycosylases, which are oxidized-lesion specific enzymes that catalyze the first step of BER. Furthermore, we are interested in three aspects of NEIL-enzyme regulation including (1) identifying the subcellular localization of NEIL enzymes in response to oxidative stress, (2) regulation of NEIL activity by post- translational modifications, and (3) structure-driven functional studies that seek to identify unique protein interacting partners of the NEIL enzymes, which are essential for successful repair (Fig. 1). These aspects are intimately involved with understanding the role of environmental factors in driving mutagenesis.
More recently, my laboratory has been involved with performing experiments to aid in the reclassification of variants of uncertain significance (VUS) in mismatch repair genes whose loss of function leads to a hereditary cancer syndrome known as Lynch syndrome (LS). VUSs are challenging for patient medical management as functional information regarding the variant is unavailable. The focus of my lab is to use functional assays to recharacterize VUSs as either pathogenic (leads to a higher risk for disease) or benign (not disease causing) (Fig. 2). We are currently extending these studies to analyze the contribution of environmental toxicants such as cadmium (a known carcinogen) in driving cancer progression in LS patients.