My work has focused on translational research in DNA damage and repair, specifically, to determine how those activities can be exploited therapeutically to treat cancers and protect normal cells from oxidative and DNA base damage. Since 1993, I have focused specifically on the enzyme apurinic/apyrimidinic endonuclease 1/ Redox effector factor-1 (APE1/Ref-1)—mechanistically as well as a therapeutic target in cancers and other diseases that manifest cancer-like properties. APE1/Ref-1 is unique to the Base Excision Repair Pathway (BER), with dual repair and redox signaling functions that are crucial to cellular viability. My work has been the first to tease apart those functions, not only to fully characterize them, but to also determine how to manipulate each function individually for therapeutic benefit. In doing the latter, I discovered and have been developing a redox-specific inhibitor of Ref-1, as well as second-generation analogs that are under further investigation. This original work was the impetus for becoming Chief Scientific Founder and Officer of Apexian Pharmaceutical, an integrated drug development company that’s leveraging the APE1/Ref-1 target platform to produce new therapeutics for some of the deadliest and hardest-to-treat cancers. Apexian recently submitted and received a treatment IND (IND125360) for a new drug that targets Ref-1; its potential indications include ovarian, colon, pancreatic cancer, leukemias as well as other adult and pediatric cancers. APX3330 is completing a phase 1 clinical trial for safety and recommended Phase II dose (RP2D) in cancer patients (NCT03375086). I am also exploring APE1/Ref-1 and BER for mechanistic and therapeutic opportunities in chemotherapy-induced peripheral neuropathy (CIPN) and other diseases. In broader terms, all the academic chairs I’ve held and the program leader and director positions I currently hold are dedicated to fast-tracking collaboration and translational research to find more effective cancer treatments. In my Associate Director positions, I also help equip the next generation of researchers by training and mentoring junior faculty, postdoctorates, fellows, MD students and others. My expertise in Ref-1 functions, drug development, such as taking APX3330 to clinical trials and development of second generation compounds, as well as years of studies centering on Ref-1 and its role as a node in cancer cells will augment this application.
I serve on numerous consulting/scientific boards of several biotechnology companies and have and still serves on various NIH/NCI study sections and Cancer Center review panels. I was chair of the Cancer Etiology Study Section at NIH and reviews for numerous international agencies. I am a member of American Association for the Advancement of Science, American Association for Cancer Research, Society for Pediatric Research, and American Society of Clinical Oncology. I also serve on the editorial board of Frontiers in Bioscience, Journal of Pharmacology and Experimental Therapeutics, Mutation Research; Molecular and Fundamental Mechanisms (Assoc Editor) and Current Molecular Pharmacology.
1993–1998 Associate Professor of Pediatrics, Section of Pediatric Endocrinology and Dept. of Biochemistry and Molecular Biology, Indiana University School of Medicine (IUSM)
1995– 2017 Associate Director, Wells Center for Pediatric Research, IUSM
1997–present Professor of Pediatrics and Dept. of Biochemistry and Molecular Biology, IUSM
2001–2006 Program Leader, Experimental and Developmental Therapeutics Research, IUSCC, IUSM
2002–2006 Chemical Pathology Study Section Member & Cancer Etiology Study Section Member
2004–2006 Cancer Etiology Study Section Chairperson
2008–2012 NCI-F Manpower and Training: T32 Training grant and K99/R00 Career development Awards
2001–2008 Jonathan and Jennifer Simmons Professor of Pediatrics, Dept. of Pediatrics, IUSM
2002–present Professor, Dept. of Pharmacology and Toxicology, Indiana University School of Medicine
2005–present Associate Director of Basic Science Research, Indiana University Simon Cancer Center
2006–present Chair, IU Simon Cancer Center Translational Research Acceleration Collaboration (ITRAC)
2008–present Director, Program in Pediatric Molecular Oncology and Experimental Therapeutics, IUSM
2008–present Betty and Earl Herr Chair in Pediatric Oncology Research
2008–present Chief Scientific Founder and Officer, Apexian Pharmaceuticals, Indianapolis, IN
2012–2016 Co-Director, Chemical Biology and Drug Discovery Initiative, IU Simon Cancer Center
2012–2016 NCI-F Grant Review SEP: Cancer Health Disparities/Diversity in Basic Cancer Research
2013–2016 Chair, NCI Omnibus Special Emphasis Panel: drug discovery reviews
2017—present Member, Basic Mechanisms of Cancer Therapeutics (BMCT) Study Section, NIH
2004-- 2018 75 NIH study section review panels over 14 years.