Projects and Grants per year
Personal profile
Research Interests
Dr. William St. Clair is a physician-scientist with a 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 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.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Residency, Massachusetts General Hospital, Boston, MA
2000
Internship, The Christ Hospital, Cincinnati, OH
1996
Doctor of Medicine, University Of Kentucky
1995
Doctor of Philosophy, University Of Iowa
1985
Master of Science, University Of Iowa
1982
Bachelor of Science, St Ambrose College
1978
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Collaborations and top research areas from the last five years
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Feasibility and Safety of HyperArc Stereotactic Radiosurgery/Radiotherapy for Intraocular Malignancy
Pokhrel, D. (PI) & St Clair, W. (CoI)
4/1/25 → 10/1/26
Project: Research project
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22-MULTI-55-FP-PMC (FPI-2059-101): A Phase 1 Study of [225AC]-FPI-2059 In Adult Participants with NTSR1-Expressing Advanced, Metastatic and/or Recurrent Solid Tumours
St Clair, W. (PI) & Kunos, C. (Former PI)
12/20/22 → 10/4/25
Project: Research project
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Targeting Mitochondrial Redox Capacity to Overcome Cancer Subtype that Regrowth After Radiation
Chaiswing, L. (PI), Higashi, R. (CoI), Luo, W. (CoI), St Clair, W. (CoI) & Weiss, H. (CoI)
4/1/21 → 3/31/26
Project: Research project
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University of Kentucky Center for Cancer and Metabolism
St Clair, D. (PI), Anthony, L. (CoI), Arnold, S. (CoI), Black, W. (CoI), Bollinger, L. (CoI), Butterfield, D. A. (CoI), Chaiswing, L. (CoI), Chen, M. (CoI), Fan, W.-M. (CoI), Gao, T. (CoI), Higashi, R. (CoI), Jia, J. (CoI), Kyprianou, N. (CoI), Lane, A. (CoI), Lee, E. (CoI), Long, D. (CoI), Morris, A. (CoI), Moseley, H. (CoI), O'Connor, K. (CoI), Peterson, C. (CoI), Piecoro, D. (CoI), Powell, D. (CoI), Romond, E. (CoI), St Clair, W. (CoI), Thomas, D. (CoI), Vanderford, N. (CoI), Wang, C. (CoI), Weiss, H. (CoI), Wu, Y. (CoI), Yu, G. (CoI), Zaytseva, Y. (CoI), Zhou, B. (CoPI), Dobrowolski, P. (Former CoI) & Xu, R. (Former CoI)
National Institute of General Medical Sciences
3/1/17 → 12/31/17
Project: Research project
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University of Kentucky Center for Cancer and Metabolism
St Clair, D. (PI), Anthony, L. (CoI), Arnold, S. (CoI), Black, W. (CoI), Bollinger, L. (CoI), Chaiswing, L. (CoI), Fan, W.-M. (CoI), Gao, T. (CoI), Higashi, R. (CoI), Jia, J. (CoI), Lane, A. (CoI), Lee, E. (CoI), Long, D. (CoI), Morris, A. (CoI), Moseley, H. (CoI), Peterson, C. (CoI), Powell, D. (CoI), St Clair, W. (CoI), Vanderford, N. (CoI), Wang, C. (CoI), Weiss, H. (CoI), Xu, R. (CoI), Yu, G. (CoI), Zaytseva, Y. (CoI), Zhou, B. (CoI), Brainson, C. (Former CoI), Kyprianou, N. (Former CoI), Thomas, D. (Former CoI) & Zhu, H. (Former CoI)
National Institute of General Medical Sciences
3/1/17 → 12/31/19
Project: Research project
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A knowledge-based planning model to identify fraction-reduction opportunities in brain stereotactic radiotherapy
McCarthy, S., St. Clair, W. & Pokhrel, D., Apr 2025, In: Journal of Applied Clinical Medical Physics. 26, 4, e70055.Research output: Contribution to journal › Article › peer-review
Open Access -
An investigation into the feasibility and efficacy of stereotactic radiosurgery for 1–3 cm single brain lesions on the ring-mounted Halcyon LINAC
Hazelwood, K., McCarthy, S., Misa, J., Castelvetere, D., St. Clair, W. & Pokhrel, D., 2025, (Accepted/In press) In: Journal of Applied Clinical Medical Physics.Research output: Contribution to journal › Article › peer-review
Open Access -
Automated hippocampal sparing whole brain radiotherapy with simultaneous integrated boost for multiple brain metastases: Halcyon, HyperArc on TrueBeam, and coplanar TrueBeam
McCarthy, S., Clark, R., Magliari, A., St. Clair, W. & Pokhrel, D., Feb 2025, In: Journal of Applied Clinical Medical Physics. 26, 2, e14570.Research output: Contribution to journal › Article › peer-review
Open Access -
Development and clinical implementation of a comprehensive multifractionation scheme HyperArc-based RapidPlan model for single and multiple brain metastases
McCarthy, S., Clair, W. S. & Pokhrel, D., 2025, (Accepted/In press) In: Medical Dosimetry.Research output: Contribution to journal › Article › peer-review
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In Vitro α/β Ratio Variations in Cervical Cancer, with Consequent Effects on Equivalent Dose in 2 Gy Fraction in High-Dose-Rate Brachytherapy
Thayer-Freeman, C., Washington, B., Fabian, D., Cheek, D., Clair, W. S., Bernard, M. & Luo, W., Mar 2025, In: Advances in Radiation Oncology. 10, 3, 101725.Research output: Contribution to journal › Article › peer-review
Open Access