Member Biography

Mark R. Kelley, Ph.D.
Mark Kelley

Mark Kelley, Ph.D.

Cancer Research Institute
1044 W. Walnut St., R4 302
Indianapolis, IN 46202
Phone: (317) 274-2755

Research Program Membership

Full member:

Betty and Earl Herr Professor of Pediatric Oncology Research
Department of Pediatrics
IU School of Medicine

Professor of Pediatrics
Department of Pediatrics
IU School of Medicine

Professor of Biochemistry and Molecular Biology
Department of Biochemistry and Molecular Biology
IU School of Medicine

Adjunct Professor of Pharmacology and Toxicology
Department of Pharmacology and Toxicology
IU School of Medicine

Associate Director of Basic Science Research
IU Simon Cancer Center

Dr. Kelley's research interests include:

The inherent chemical instability of DNA, the production of reactive oxygen species during normal cellular metabolism, and the continuous exposure to environmental mutagens and extraneous agents, such as during cancer therapy, all represent a potential threat to the integrity of the DNA of cells. Recently, we have focused more specifically on the role of the major apurinic endonuclease DNA repair enzyme, APE1/Ref-1, in cancer both as a diagnostic and therapeutic factor and are studying the role of DNA BER and specifically APE1/Ref-1 as both a DNA repair and redox signaling factor for normal and cancer cells. We and others have shown that the Ape1/Ref-1 protein is significantly and dramatically elevated in pediatric and adult brain tumors, osteosarcomas and rhabdomyosarcomas, ALL, pancreatic cancer, ovarian, prostate, cervical and germ cell tumors. We are currently trying to understand APE1/Ref-1's role in these cancers and others, and determining how to modulate its activity for therapeutic applications (small molecule inhibitors). Our primary focus is currently directed toward pediatric and adult gliomas, pediatric leukemia/neuroblastoma, and pancreatic cancer:

  • Molecular and cellular biology, biochemistry and translational applications of eukaryotic DNA base excision repair (BER).
  • Regulation and function of AP endonuclease (Ape1/Ref-1) in normal and cancer cells. The multifunctional mammalian APE1 is responsible for the repair of AP (abasic) sites in DNA.
  • APE1/Ref-1 is a multifunctional protein that has also been shown to function as a redox factor facilitating the DNA-binding capability of numerous transcription factors (Fos, Jun, HIF-1, PAX, NFkB, STAT3) as well as p53.
  • Studies of DNA repair genes involved in repairing base damage that occurs from oxidative and alkylation events in normal and tumor cells.
  • Studies relating to DNA damage and repair of neuronal cells resulting in chemotherapy induced peripheral neuropathy (CIPN); peripheral neuropathy and cognitive dysfunction ("chemobrain")
  • Cross-talk between the BER and the NER DNA repair pathways in peripheral neurons.
  • Redox signaling in mammalian cells.
  • Anti-angiogenesis therapeutics in cancer and non-cancer systems including macular degeneration and neo-vascularization.
  • Identification and development of small molecule inhibitor's of both APE1/Ref-1's redox signaling and DNA repair functions.
  • Continued development of APX3330, a small molecule that blocks APE1/Ref-1's redox function for Phase I and eventual Phase II trials in pancreatic cancer and other indications.

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Post-doctoral Fellowship - The Rockefeller University, New York, NY 1984-1987

Ph.D. - Louisiana State University, Baton Rouge, LA 1984

M.S. - Louisiana State University, Baton Rouge, LA 1981

B.A. - DePauw University, Greencastle, IN 1979