Edward A. Motea
Assistant Professor of Biochemistry & Molecular Biology
Dr. Motea received his PhD in Chemistry from Case Western Reserve University under the directions of Dr. Irene Lee and Dr. Anthony Berdis through the Cancer Pharmacology Training Program. His graduate research focused on understanding how DNA polymerases select nucleotides during the replication bypass of damaged DNA (e.g., oxidatively damaged nucleobase and abasic sites). This aberrant process, also known as translesion DNA synthesis or TLS, remains a critical means of survival and drug resistance for cancer cells following therapy, which makes it an interesting pathway to study for innovative targeted therapeutic interventions. His graduate research areas included application of medicinal chemistry, computational chemistry, chemical biology, enzyme kinetics, and molecular biology to rationally design and synthesize novel non-natural nucleosides and nucleotides as biochemical probes and theranostic agents (a chemical agent with dual therapeutic and diagnostic capabilities). Dr. Motea pursued his postdoctoral fellowship at UT Southwestern Medical Center/Simmons Comprehensive Cancer Center under Dr. David Boothman in the Departments of Pharmacology and Radiation Oncology where he received a Cancer Biology Training Grant (PD: Dr. Jerry T. Shay) to investigate the functional role (i.e., structure-function relationship studies) of novel factors (e.g., Kub5-Hera, XRN2, p15RS, and NQO1) that could be exploited as predictive biomarkers for targeted therapy. He joined the faculty of Chemical Biology and Biotherapeutics within the Department of Biochemistry and Molecular Biology at Indiana University School of Medicine in 2017. Dr. Motea has two broad areas of research interest. The first area focuses on understanding the mechanistic basis for the pathophysiological role of persistent RNA:DNA hybrid structures (also known as R-loops) as a source of DNA damage and genomic instability focusing on the novel functional roles of transcription termination factors in DNA repair. His second area of interest is in developing novel chemical agents and innovative strategies based on mechanistic studies to potentiate the tumor-selective effects of NQO1-bioactivatable drugs focusing on understanding the mechanism of action/synergy to enhance tumor lethality while sparing normal tissues. His research incorporates interdisciplinary approaches to biological questions ranging from synthetic/medicinal chemistry to cancer biology and therapeutics.
The major goal of Dr. Motea’s research lab is to discover and understand at the molecular level how cancer cells promote and/or avert critical mechanisms of survival and growth following therapy. Specifically, his research will focus on (1) discovering and characterizing novel factors and phenomenon in damaged DNA replication and repair; (2) understanding the role of persistent DNA:RNA hybrids or R-loops in genomic instability; and (3) elucidating the mechanistic basis for NQO1-bioactivable drug synergy with novel and current FDA-approved anticancer agents. Overall, the mechanistic insights gained from his research program should ultimately lead to the development of novel chemical agents, biomarkers, druggable targets and innovative strategies to selectively stop malignant cells while sparing healthy cells for personalized medicine in the clinic.