Barry R. O'Keefe, Ph.D.

Senior Scientist

Molecular Targets Program


Building 576, Room 101
Frederick, MD 21702-1201


Research Topics

Our research efforts are generally split into two study areas: 1) cell-free assay development and identification of active compounds from chemical and natural product libraries, and 2) the isolation and characterization of antiviral proteins from natural product extracts. In the first, our goals are to understand and define specific protein-ligand interactions and use that knowledge to adapt laboratory findings into both high-throughput screens and potential therapeutic discoveries. In the second, we carry out independent research on the discovery and characterization of novel antiviral proteins from natural products extracts. This research is necessarily multidisciplinary and collaborative both within the Molecular Targets Program, as well as the NCI, the NIH and with extramural collaborators interested in our scientific discoveries. Our group uses its expertise in protein chemistry, enzymology, molecular biology, natural products research and assay development to identify, isolate and biochemically characterize new bioactive moieties.


Dr. O'Keefe earned a Bachelor of Science degree in botany from Michigan State University and a Ph.D. in pharmacognosy from the University of Illinois at Chicago. In 1994 Dr. O'Keefe joined the NCI Laboratory of Drug Discovery Research and Development to study novel proteins from natural products extracts. Dr. O'Keefe is currently Director of the Molecular Targets Program and Head of the Protein Chemistry and Molecular Biology Section. Dr. O'Keefe is also Chief of the Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, NCI.

Selected Publications

  1. Cai S, Risinger AL, Petersen CL, Grkovic T, O'Keefe BR, Mooberry SL, Cichewicz RH. Anacolosins A-F and Corymbulosins X and Y, Clerodane Diterpenes from Anacolosa clarkii Exhibiting Cytotoxicity toward Pediatric Cancer Cell Lines. J Nat Prod. 2019;82(4):928-936.
  2. Grkovic T, Evans JR, Akee RK, Guo L, Davis M, Jato J, Grothaus PG, Ahalt-Gottholm M, Hollingshead M, Collins JM, Newman DJ, O'Keefe BR. Erythrofordins D and E, two new cassaine-type diterpenes from Erythrophleum suaveolens. Bioorg Med Chem Lett. 2019;29(2):134-137.
  3. Matarlo JS, Krumpe LRH, Heinz WF, Oh D, Shenoy SR, Thomas CL, Goncharova EI, Lockett SJ, O'Keefe BR. The Natural Product Butylcycloheptyl Prodiginine Binds Pre-miR-21, Inhibits Dicer-Mediated Processing of Pre-miR-21, and Blocks Cellular Proliferation. Cell Chem Biol. 2019;26(8):1133-1142.e4.
  4. Thornburg CC, Britt JR, Evans JR, Akee RK, Whitt JA, Trinh SK, Harris MJ, Thompson JR, Ewing TL, Shipley SM, Grothaus PG, Newman DJ, Schneider JP, Grkovic T, O'Keefe BR. NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening. ACS Chem Biol. 2018;13(9):2484-2497.
  5. Jia L, Lin H, Oppenheim J, Howard OMZ, Li J, Fan H, Zhao Z, Farrar W, Zhang Y, Colburn N, Young MR, Li W, Newman D, O'Keefe BR, Beutler J, Liu J, Hao X, Yang X, Ji T, White JD. US National Cancer Institute-China Collaborative Studies on Chinese Medicine and Cancer. J Natl Cancer Inst Monogr. 2017;2017(52).

Related Scientific Focus Areas

This page was last updated on Monday, March 11, 2024