William H. St. Clair, MD, PhD

  • Co-Director, Gamma Knife Radiosurgery Program


William H. St. Clair, MD, PhD, is a professor in the Department of Radiation Oncology at the University of Kentucky. Since coming to UK in 2000, he has served as Residency Director, Assistant and Associate Professor, and Interim Chairman for the department, as well as taking on a joint appointment in the Graduate Center for Nutritional Sciences. Dr. St. Clair previously worked as Assistant Professor of Radiology at the Bowman Gray School of Medicine at Wake Forest University, a Research Fellow in the Department of Cancer Biology, Laboratory of Radiobiology, at the Harvard School of Public Health, a Cancer Center Research Assistant at the University of Iowa, and as a Quality Control Chemist at First Mississippi Inc.

Dr. St. Clair completed his residency in radiation oncology at Massachusetts General Hospital and interned in the Department of Internal Medicine at The Christ Hospital in Cincinnati, Ohio. He earned his BS in Biology at St. Ambrose College, his MS and PhD in Radiation Biology at the University of Iowa, and his MD at UK. Dr. St. Clair is certified in radiation oncology by the American Board of Radiology and is a member of several professional medical societies.

Having served on many board committees, Dr. St. Clair has also been a part of many published research articles and has presented on their findings at myriad societal meetings across his more than 30-year career. His clinical interested include genitourinary and central nervous system neoplasms.

Outside of medicine, Dr. St. Clair enjoys taking hikes, particularly in state parks, and he considers himself an avid gardener.

Personal Statement: “What I like best about being in radiation oncology is two-fold: the technology is very interesting. It’s fast-moving and continuing to improve every day. And I really enjoy the very frequent patient contact. I get to see patients every day and share treatment successes with them. When I have a patient initially come to see me in a wheelchair due to the tremendous amount of pain they’re in and then get to see them up and walking after just two or three treatment sessions—it’s a very rewarding part of my job.”

Faculty Rank

  • Professor of Radiation Medicine
  • fixes empty view field issue
    Multi-disciplinary team and Gamma Knife

Training & Education


MD, University of Kentucky, College of Medicine, Lexington
PhD, University of Iowa, College of Medicine, Iowa City


Massachusetts General Hospital, Boston


Harvard University Medical Center, Boston

Certifications and Special Training

American Board of Radiology, Radiation Oncology


Research Focus

Dr. William St. Clair is a physician-scientist with principal interested in advancing the efficacy of radiation therapy for the treatment of cancers. Thus, the goal of his research project is to investigate novel approaches that can enhance cancer therapeutic efficacy while protecting normal tissues against the side effects of radiation therapy. Prostate cancer is the most frequently diagnosed cancer in men and radiation therapy is used to treat early stage and inoperable, locally advanced prostate cancer. Although current radiation therapeutic strategies are very effective and successful in treating the initial cancer, treating patients who have unfavorable tumors remains a major concern. A goal of his research projects is to use mechanistic based, bench to bedside approaches to obtain novel insights into the mechanisms of prostate cancer resistant to radiation therapy. We have identified the alternative pathway of the nuclear factor kappa beta (NF-κB) as a major contributor to prostate cancer growth and progression. We have demonstrated that: 1) aggressive prostate cancers have high nuclear RelB, a member of the alternative pathway of NF-κB; 2) suppression of RelB in androgen independent-aggressive prostate cancer cells results in reduction of interleukin 8 (IL8) levels in tumor cells and reduced tumor growth in vivo; 3) overexpression of RelB in androgen responsive prostate cancer cells results in enhanced tumor growth and production of IL8 but reduced prostate specific androgen (PSA) production; and 4) suppression of RelB nuclear translocation enhances radiation sensitivity of prostate cancer. Based on these important findings, we hypothesize that RelB regulates prostate cancer response to radiation via a NF-κB switch to activate expression of IL8 and suppress expression of PSA in prostate cancer cells. This study is design to develop practical predictive measures for prostate cancer diagnostic, treatment planning and surveillance. The second goal of Dr. William St. Clair research program is to identify novel mechanisms that could lead to the development of specific measures for effective treatment of aggressive prostate cancers. A growing body of data indicates that cancer has an elevated oxidative stress level compared to normal tissue. We have recently identified Parthenolide (PN), a sesquiterpene lactone derived from the leaves of the traditional herbal medicine feverfew, as having a differential effect on the sensitivity of prostate cancer cells versus normal prostate epithelial cells to ionizing radiation. PN increase superoxide production in cancer cells via an NADPH oxidase dependent activation of the PI3K-AKT pathway, resulting in down-regulation of the FOXO3-activated antioxidants; inactives NF-κB transcriptional function; and inhibits Keap 1 dependent NRF2 activation in cancer cells but activates NRF2 function in normal cells. We are conducting a series of experiments to test this novel concept in an experimental therapeutic setting and investigate the mechanisms linking RelB levels to oxidative stress overload and invasive properties of prostate cancer.

Contact Information

800 Rose Street
Lexington, KY 40536
United States



  1. Suppression of DMH-induced liver carcinogenesis in mice by dietary addition of the Bowman-Birk protease inhibitor.
    St. Clair WH, Billings PC, Carew JA, Keller-McGandy C, Newberne P, and Kennedy AR. Cancer Res 50:580-586, 1990.
  2. Prevention of acute radiation-induced proctosigmoiditis by balsalazide: a randomized, double-blind, placebo controlled trial in prostate cancer patients.
    Jahraus CD, Bettenhausen D, Malik U, Sellitti M, and St. Clair WH. Int J Radiation Oncology Biol Phys 63:1483-1487, 2005.
  3. Selective inhibition of RelB suppresses intrinsic radiation resistance in prostate cancer cells.
    Josson S, Xu Y, Fang F, Dhar SK, St. Clair DK, and St. Clair WH. Oncogene 25:1554-1559, 2006.
  4. A NADPH Oxidase-Dependent Redox Signaling Pathway Mediates the Selective Radiosensitization Effect of Parthenolide in Prostate Cancer Cells.
    Sun Y, St. Clair DK, Xu Y, Crooks PA, St. Clair WH. Cancer Res 70(7):2880-90, 2010.
  5. Long-term Outcome of High-Dose Gamma Knife Surgery in Treatment of Trigeminal Neuralgia.
    Young B, Shivazad A, Kryscio RJ, St. Clair W, Bush HM. J Neurosurg, 2013.