Featured Scholar: Mark Kelley, PhD
Betty and Earl Herr Professor in Pediatric Oncology Research
Associate Director of Basic Science Research, Indiana University Simon Comprehensive Cancer Center
Professor, Departments of Pediatrics, Biochemistry & Molecular Biology, Pharmacology & Toxicology and Ophthalmology
Adjunct Professor, Eugene and Marilyn Glick Eye Institute
Director, Program in Pediatric Molecular Oncology & Experimental Therapeutics
Glenn W. Irwin, Jr. M.D. Research Scholar
Bantz-Petrino Translating Research into Practice Scholar
Mark R. Kelley, Ph.D., is the Associate Director of Basic Science at Indiana University Simon Comprehensive Cancer Center (IUSCCC) and the Betty and Earl Herr Professor in Pediatric Oncology Research and Professor, Department of Pediatrics. He is also Professor in Ophthalmology, Biochemistry & Molecular Biology, Pharmacology & Toxicology and Adjunct Professor, Eugene and Marilyn Glick Eye Institute as well as the Glenn W. Irwin, Jr. M.D. Research Scholar, Bantz-Petrino Translating Research into Practice Scholar and AAAS Science Fellow. He co-leads the Cancer Drug Discovery and Development Program (CDDD) in the IUSCCC.
His 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 1990, he has 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. He has concentrated on teasing apart these functions and in the process, has discovered and hasbeen developing redox-specific inhibitors of Ref-1. This original work was the impetus for becoming Chief Scientific Founder and Officer of Apexian Pharmaceutical targeting Ref-1 to produce new therapeutics for some of the deadliest and hardest-to-treat cancers. Apexian recently completed a phase I clinical trial using oral APX3330 in solid tumor patients (NCT03375086). This trial established safety, expected PK, target engagement, and responses in patients in the trial. Phase II trials are being developed in cancer and other indications including ocular diseases. A phase II trial using APX3330 in diabetic retinopathy (DR) recently began accruing patients (NCT04692688) using a drug he developed and licensed to Ocuphire Pharma. In broader terms, all the academic chairs he has held and the program leader and director positions he currently holds are dedicated to fast-tracking collaboration and translational research to find more effective cancer treatments. He is also the PI of the IUSCCC ACS Institutional training grant and is directing the Cancer Drug Discovery and Development (CDDD) program in the IU Simon Comprehensive Cancer Center (IUSCCC) and am a member of the CTSA drug discovery “think-tank” at the IU School of Medicine. In all his leadership positions, he also help equips the next generation of researchers by training and mentoring graduate students, MD and MSTP students, junior faculty, post-doctorates, fellows, and others. He is also committed to Diversity, Equity, and Inclusion in his lab and this institution and strongly supports women in science as well as mentor scientists from many different backgrounds.
Professor Kelley's work to find more effective cancer treatments is another example of how IUPUI's faculty members are TRANSLATING their RESEARCH INTO PRACTICE.
Selected Publications in IUPUI ScholarWorks
With over 75 scholarly articles contributed to IUPUI's free, open access repository, Dr. Kelley has made research knowledge about the role of the DNA repair enzyme APE1/Ref-1 in cancer therapy available available to researchers, students and readers around the world.
Shah, F., Goossens, E., Atallah, N. M., Grimard, M., Kelley, M. R., & Fishel, M. L. (2017). APE1/Ref-1 knockdown in pancreatic ductal adenocarcinoma - characterizing gene expression changes and identifying novel pathways using single-cell RNA sequencing. Molecular Oncology. Available from: http://hdl.handle.net/1805/14364
Shah, F., Logsdon, D., Messmann, R. A., Fehrenbacher, J. C., Fishel, M. L., & Kelley, M. R. (2017). Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic. Npj Precision Oncology, 1(1), 19. Available from: http://hdl.handle.net/1805/14363
Ding, J., Fishel, M. L., Reed, A. M., McAdams, E., Czader, M., Cardoso, A. A., & Kelley, M. R. (2017). Ref-1/APE1 as Transcriptional Regulator and Novel Therapeutic Target in Pediatric T-cell Leukemia. Molecular Cancer Therapeutics, molcanther.0099.2017. Available from: http://hdl.handle.net/1805/14366
Kelley, M. R., & Fehrenbacher, J. C. (2017). Challenges and opportunities identifying therapeutic targets for chemotherapy-induced peripheral neuropathy resulting from oxidative DNA damage. Neural Regeneration Research, 12(1), 72–74. Available from: http://hdl.handle.net/1805/13725
Logsdon, D. P., Grimard, M., Luo, M., Shahda, S., Jiang, Y., Tong, Y., … Fishel, M. L. (2016). Regulation of HIF1α under Hypoxia by APE1/Ref-1 Impacts CA9 Expression: Dual Targeting in Patient-Derived 3D Pancreatic Cancer Models. Molecular Cancer Therapeutics, 15(11), 2722–2732. Available from: http://hdl.handle.net/1805/14361
Georgiadis, M. M., Chen, Q., Meng, J., Guo, C., Wireman, R., Reed, A., … Kelley, M. R. (2016). Small molecule activation of apurinic/apyrimidinic endonuclease 1 reduces DNA damage induced by cisplatin in cultured sensory neurons. DNA Repair, 41(Supplement C), 32–41. Available from: http://hdl.handle.net/1805/13825
Kelley, M. R., Wikel, J. H., Guo, C., Pollok, K. E., Bailey, B. J., Wireman, R., … Vasko, M. R. (2016). Identification of new chemical entities targeting APE1 for the prevention of chemotherapy-induced peripheral neuropathy (CIPN). Journal of Pharmacology and Experimental Therapeutics, jpet.116.235283. Available from: http://hdl.handle.net/1805/14360
Li, Y., Liu, X., Zhou, T., Kelley, M. R., Edwards, P., Gao, H., & Qiao, X. (2014). Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization. Redox Biology, 2, 485-494. Available from: http://hdl.handle.net/1805/4698
Kelley, M. R., Georgiadis, M. M., & Fishel, M. L. (2012). APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Current Molecular Pharmacology, 5(1), 36. Available from: http://hdl.handle.net/1805/4688
Kelley, M. R. (2011). DNA repair inhibitors: Where do we go from here?. DNA Repair, 10(11), 1183. Available from: http://hdl.handle.net/1805/4687
Find more free articles by Mark R. Kelley in IUPUI ScholarWorks.