Mark R. Kelley, Ph.D.
Betty and Earl Herr Professor in Pediatric Oncology Research and Professor
Departments of Pediatrics, Biochemistry & Molecular Biology and Pharmacology & Toxicology
Associate Director, Herman B Wells Center for Pediatric Research
Associate Director of Basic Science Research, Indiana University Simon Cancer Center
Director, Program in Pediatric Molecular Oncology & Experimental Therapeutics
1044 West Walnut, R4 302
Indianapolis, IN 46202
Areas of Interest
Dr. Kelley’s laboratory studies DNA repair genes involved in repairing base damage that occurs from oxidative and alkylation events in normal and tumor cells and following cancer treatments. Ongoing projects include: 1) Studying the multifunctional Ape1/Ref-1 protein structure/function in order to determine its redox and repair functions in normal and cancer cells, 2) Molecular targeted therapeutic approaches at members of the DNA base excision repair (BER) pathway, 3) Altering Ape1’s redox function and role in angiogenesis as a therapeutic approach for cancer and other indications, 4) Role of DNA repair genes in cognitive dysfunction (“chemobrain”) and peripheral neuropathy.
Mark R. Kelley, PhD has been part of the IU School of Medicine Department of Pediatrics since 1993 and is currently the Betty and Earl Herr Chair in Pediatric Oncology Research, Professor of Biochemistry and Molecular Biology, Professor of Pharmacology and Pediatrics, Associate Director for the Herman B Wells Center for Pediatric Research, and the Associate Director of Basic Science Research at the Indiana University Melvin and Bren Simon Cancer Center. He received his B.A. from DePauw University and his MS and PhD from Louisiana State University. He then trained as a postdoctoral fellow at The Rockefeller University in New York City and from there he became an assistant professor at the Biochemistry Department at Loyola University Medical School before joining the IUSM.
All of the discoveries gained during Dr. Kelley’s research have culminated in 14 patents and over 160 articles in peer reviewed journals, plus numerous reviews (over 18) on the topic of APE1/Ref-1 for both its repair and redox activities and clinical/translational relevance attesting to my contributions to that field of knowledge. In 2001, he received the Jonathan and Jennifer Simmons Chair in Pediatrics, given to an investigator who is a strong proponent and contributor in the area of translational cancer research, a position he held until 2008 when he was awarded the Betty and Earl Herr Chair in Pediatric Oncology Research. He sits on several editorial boards, has sat on numerous NCI review panels, and is the Chief Scientific Founder of ApeX Therapeutics (http://apextherapeutics.com/), an integrated drug development company built to leverage the APE1 target platform to produce new therapeutics to meet unmet needs in cancer.
|1979||BA- Zoology Depauw University|
|1981||MS- Zoology Louisiana State University|
|1984||PhD- Genetics Louisiana State University|
|1987||Postdoctorate The Rockefeller University|
Honors & Awards
- Malpas Trust Scholarship 1975-1979
- McClure Research Fellowship 1979
- National Sigma XI Research Grant 1982-1983
- American Cancer Society Postdoctoral Fellowship 1984-1987
- Schweppe Career Development Award 1989-1992
- Jonathan and Jennifer Simmons Professor of Pediatrics 2001-2008
- Betty and Earl Herr Chair in Pediatric Oncology Research 2008 - Present
Riley Outpatient Center
705 Riley Hospital Drive
Indianapolis, IN 46202
Research & Grants
Novel Role of Ref-1 in Pancreatic Etiology and Progression
R01 CA167291-01A1 01/01/13-12/31/17
Goals: Study the role and interaction of Ref-1 in tumor and stroma of PDAC.
Novel Therapeutic Strategy for Refractory and Relapse Childhood Acute Leukemia
Goals: Develop newly discovered Ref-1 redox inhibitors for clinical trials
Studies to Support Clinical Translation of a Novel Ref-1-Targeted Therapy for Relapsed Childhood Acute Lymphoblastic Leukemia
09/01/13 – 12/01/15
Hyundai Hope on Wheels
Kelley / Cardoso / Batra (co-PIs)
Goals: Basic and translational mechanisms of Ref-1 in relapsed and refractive ALL
Testing ApeX compounds for efficacy in leukemia models
ApeX Therapeutics Contract
Goals: Testing new Ref-1 redox inhibitors in leukemia models for efficacy
IU Simon Cancer Center Institutional Research Grant
American Cancer Society
Goals: Institutional ACS grant to furnish young investigators with pilot funding
Cancer Center Support Grant
P30 CA082709-14 09/01/08-08/31/19
Role: Associate Director of Basic Science
Indiana Clinical and Translational Sciences Institute
8UL1TR000006-05 05/01/08 – 04/30/13
Role: Co-Director of the TRAC 1 program
To establish a new institute that facilitates clinical and translational biomedical research across the state of Indiana. This is an institute established by the CTSA to Indiana and Purdue Universities.
Indiana Medical Scientist/Engineer Training Program
GM077229-01A1 07/01/08 – 06/30/14
Project: Train engaging physician-scientist who are poised to pursue careers as clinical investigators in hypothesis-driven, investigator-initiated research.
Basic Science Studies on Gene Therapy of Blood Diseases
2T32HL007910 07/01/1999 – 08/31/14
To continue training the next generation of scientists in the clinically-relevant medical area of gene transfer for effective modulation of normal cell growth, and gene therapy
IUPUI Pancreatic Cancer Signature Center: Designation and Funding for Pancreatic Cancer Working Group
IUPUI Signature Center Initiative
Goals: Support for pancreatic working group; infrastructure, models, primary panc lines and tissues as well as GEM models
Novel Therapeutics Strategy for Refractory and Relaspe Childhood ALL
IU Simon Cancer Center
Goals: Mechanism of APE1 function in ALL models
Chemotherapy Induced Peripheral Neuropathy
01/01/13 – 12/31/14
Goals: Mechanistic investigation of important DNA repair pathways in the quest to understand chemotherapy?induced peripheral neuropathy (CIPN)
Indiana Clinical and Translational Sciences Institute – K12 Program
KL2RR025760 05/1/08 – 4/30/18
To establish a new training and career development program providing mentoring programs and individual K08, K23, and K30 equivalent awards to junior investigators in clinical and translational biomedical research within the Indiana CTSI.
Indiana Clinical and Translational Sciences Institute – T32 Program
TL1RR025759 05/01/08 – 04/30/18
To establish a new training program providing mentoring programs and individual training fellowships to pre- and post-doctoral candidates in clinical and translational research programs within the Indiana CTSI.
Fishel ML, Colvin ES, Luo M, Kelley MR, Robertson KA (2010) Inhibition of the Redox Function of APE1/Ref-1 in Myeloid Leukemia Cell Lines Results in a Hypersensitive Response to Retinoic Acid-induced Differentiation and Apoptosis. Experimental Hematology. Dec; 38(12):1178-88. PMCID: PMC2998713
Kelley MR, Luo M, Reed A, Su D, Delaplane S, Borch R F, Nyland II RL, Gross ML, Georgiadis M. (2011) Functional analysis of new and novel analogs of E3330 that block the redox signaling activity of the multifunctional AP endonuclease/redox signaling enzyme APE1/Ref-1. Antioxid Redox Signal. April; 14(8): 1387-1401. PMCID: PMC3061197
Su D, Delaplane S, Luo M, Rempel D, Vu B, Kelley MR, Gross ML, Georgiadis M. (2011) Interactions of APE1with a redox inhibitor: Evidence for an alternate conformation of the enzyme. Biochemistry. 50(1): 82-92. PMCID: PMC3070192
Vasko MR, Guo C, Thompson EL, Kelley MR. (2011) The repair function of the multifunctional DNA repair/redox protein APE1 is neuroprotective after ionizing radiation. DNA Repair 10: 942-952. PMCID: PMC3162094
Fishel ML, Jiang Y, Rajeshkumar NV, Scandura G, Sinn AL, He Y, Shen C, Jones DR, Pollok KE, Ivan M, Maitra A, Kelley MR. (2011). Impact of APE1/Ref-1 Redox Inhibition on Pancreatic Tumor Growth. Molecular Cancer Therapeutics. Sep;10(9):1698-708.PMCID: PMC3170439
Kelley MR, Georgiadis MM, Fishel ML. (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): 36-53. PMCID: PMC3319314.
Luo M, Zhang J, He H, Su D, Chen Q, Gross M, Kelley MR, Georgiadis, M. (2012) Characterization of the Redox Activity and Disulfide Bond Formation in Apurinic / Apyrimidinic Endonuclease. Biochemistry. Jan 17; 51(2):695-705. PMCID: PMC3293223
Cardoso AA, Jiang Y, Luo M, Reed AR, He Y, Kelley MR, Fishel ML. (2012) APE1/Ref-1 Regulates STAT3 Transcriptional Activity and APE1/Ref-1-STAT3 Dual-Targeting Effectively Inhibits Pancreatic Cancer Cell Survival. PLos One, (10): e47462 PMCID: PMC3477158
Zhang J, Luo M, Marascot D, Logsdon D, LaFavers KA, Chen Q, Reed A, Kelley MR, Gross ML, Georgiadis MM. (2013) Inhibition of Apurinic/apyrimidinic endonuclease I’s redox activity revisited. Biochemistry. Apr 30;52(17):2955-66 PMCID: PMC3706204
Domenis R, Bergamin N, Gianfranceschi G, Vascotto C, Romanello M, Vagnarelli G, Faggiani M, Kelley MR, Beltrami CA, Cesselli D, Tell G, Beltrami AP. (2014) The redox function of APE1 is involved in the differentiation process of stem cells toward a neuronal cell fate. PLoS ONE, Feb 19;9(2):e89232. doi: 10.1371/journal.pone.0089232. PMCID: PMC3929656
Fishel ML, Devlin CM, Jiang Y, Luo M, He Y, Yu Zhangsheng, Tong Y, Lipking KP, Maitra A, Rejeshkumar NV, Wu X, Scandura G, Kelley MR, Ivan M. (2014) Apurinic/Apyrimidinic Endonuclease/Redox Factor-1 (APE1/Ref-1) redox function negatively regulates NRF2. J Biol Chemistry, in press.
Kelley MR, Logsdon D, Fishel M. (2014) Targeting DNA repair pathways for cancer treatment: what’s new? Future Oncology, in press