Basic
Science Information

Clinical Information

Cancer
Information

Interests

• Regulation of intracellular pH
• Acidification and hypoxia in human tumors
• Mechanisms of hyperthermia sensitization by acute acidification
• Control of heat shock protein synthesis and thermotolerance development
• Development of clinical protocols for thermoradiotherapy
• Radiation, checkpoints and the control of cell proliferation
• Radiation and hyperthermia biology education

Dr. Leeper received his undergraduate degree in Zoology and graduate degree in Radiation Biology from the University of Iowa in 1969 where he studied under Dr. Titus C. Evans, founding editor of Radiation Research. He did a post-doctoral fellowship with Dr. William C. Dewey at Colorado State University and then joined Dr. Simon Kramer in the newly formed Department of Radiation Therapy and Nuclear Medicine at Thomas Jefferson University in 1970. Dr. Leeper directed the department’s basic research effort and established the Laboratory of Experimental Radiation Oncology.

Dr. Leeper is one of the pioneers in basic and translational research in hyperthermia biology and thermoradiotherapy and had one of the first hyperthermia grants supported N.C.I in 1974. Research by Dr. Leeper and his colleagues lead to the definition of thermotolerance, the identification of the reversible nature of thermotolerance, the inhibitory effect of acute acidification on thermotolerance development, the inhibitory effect of hyperthermia on macromolecular synthesis, the discovery of step-down heating, and the nature of adaptation and hyperthermia resistance in cells growing in a chronically acidic environment.

Current research focuses on the mechanisms of tumor cell adaptation to growth at low extracellular pH, regulation of intracellular pH by membrane proton pumps, effect of acute acidification on heat-induced upregulation of heat shock proeins, hyperthermia response of human melanoma xenografts, tumor radiosensitization by modulation of tumor hypoxia with respiratory inhibitors and sensitization to thermoradiotherapy by hyperglycemia-induced acidification in human tumors.

Dr. Leeper was instrumental in translating basic hyperthermia research into clinical trials of thermoradiotherapy for the Radiation Therapy Oncology Group (RTOG). Well over 600 patients have been treated with thermoradiotherapy in this department. In 1986 Dr. Leeper received the American Cancer Society’s, Philadelphia Division, Annual Scientific Award for Pioneering Work in "Hyperthermia Research."

He has published over 100 peer-reviewed papers, has been principal investigator of numerous research grants from the National Cancer Institute, served on several "study sections" for the N.I.H. and for the Department of Defense and served as associate editor for scientific journals. Dr. Leeper has been a member of several committees of the RTOG and is currently a member of its Institutional Review Board (IRB). Dr. Leeper was chairman of the organizing committee and founding president of the North American Hyperthermia Society and last year served as the society’s 13th president. He has also served on the Council of the Radiation Research Society.

Wahl, M.L., Bobyock, S.B., Leeper, D.B. and Owen, C.S. (1997) Effects of 42°C hyperthermia on intracellular pH in ovarian carcinoma cells during acute or chronic exposure to low extracellular pH. Int. J. Radiat. Oncol. Biol. Phys. 39:205-212.

Owen, C.S., Pooler, P.M., Wahl, M.L., Bobyock, S.B., Coss, R.A. and Leeper, D.B. (1997) Altered proton extrusion in cells adapted to growth at low extracellular pH. J. Cell Physiol. 173:397-405.

Coss, R.A., Messinger, J.A., Wahl, M.L., Wachsberger, P.R., Leeper, D.B. and Owen, C.S. (1997) Bicarbonate-dependent proton extrusion in CHO cells adapted to growth at pH 6.7. Int. J. Hyperthermia 13:325-336.

Wachsberger, P.R., Landry, J., Storck, C., Davis, K., O'Hara, M.D., Owen, C.S., Leeper, D.B. and Coss, R.A. (1997). Mammalian cells adapted to growth at pH 6.7 have elevated HSP27 levels and are resistant to cisplatin. Int. J Hypertherm. 13:251-255.

Owen, C.S., Wahl, M.L., Pooler, P.M., Coss, R.A. and Leeper, D.B. (1998) Temporal association between alterations in proton extrusion and low pH adaptation. Int. J. Hypertherm. 14:227-232.

Leeper, D.B., Engin, K., Wang, J., and Li, D.J. (1998) Effect of I.V. Glucose vs combined I.V. glucose plus oral glucose on human tumor extracellular pH for potential sensitization to thermo-radiotherapy. Int. J. Hyperthermia 14:257-269..

Pooler, P.M., Wahl, M.L., Briand, P., Leeper, D.B. and Owen, C.S. (1998) Intracellular pH regulation as a function of extracellular pH in a human premalignant and malignant breast cancer cell line. J. Cell Physiol. (accepted).

Waterman, F.M., Komarnicky, L. and Leeper, D.B.(1998) Changes in human tumor blood flow and pH during fractionated course of thermoradiotherapy. Int. J. Hyperthermia (in press).

Leeper, D.B., Engin, K., Dover, J.D., Wang, J. & Li, D.J. (1998) Effect of insulin on human tumor extracellular pH during hyperglycemia. Intl. J. Hyperthermia (in press).

Biaglow, J., Manevich, Y., Leeper, D.B., Chance, B., et al. (1998) MIBG inhibits respiration: Potential for radio- and hyperthermic sensitization. Int. J. Radiat. Oncol. Biol. Phys. (in press).