Email: dennis.leeper@mail.tju.edu

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, created the Laboratory of Experimental Radiation Oncology and was Director of the Division of Radiation Biology for 30 years.

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 to receive N.C.I support 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.

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." Other awards include:

1996-2000 President, North American Hyperthermia Society
1996-2001 Vice-president, Int. Assoc. Hypthermic Oncology
2000-2004 Secretary-Treasuere, Int. Assoc. Hypthermic Oncology
2001 Invited North American Lecturer, 18th Japanese Congress of Hyperthermic Oncology, Sept. 8-9, 2001, Tokyo, Japan.
2002 Eugene Robinson Award for Outstanding Scientific Achievement, North American Hyperthermia Society, 2002

Dr. Leeper has published over 100 peer-reviewed papers, been principal investigator of numerous research grants from the National Cancer Institute, served on several grant review "study sections" at the National Cancer Institute and 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. He has also served on the Council of the Radiation Research Society.

Dr. Leeper is the principal investigator of a Program Project Grant from NCI entitled "Modification of Hyperthermia Response". It is in its third funding cycle. He has been the training director and P.I. of a National Cancer Institute post-doctoral training grant since 1985 and supervises the radiation biology education program for department of radiation oncology residents. He has trained numerous undergraduate and graduate students, post-doctoral fellows and radiation oncology residents.

Dr. Leeper's current research programs include:

• Effect of Acute Acidification on Hyperthermia Response of Human Melanoma Xenografts
• Radiosensitization by Modulation of Tumor Hypoxia with Respiratory Inhibitors
• Sensitization to Thermoradiotherapy by Hyperglycemia-induced Acidification in Human Tumors
• Stem cell expansion, radiosensitization and response to inhibition of Cox-2 in crypts of APCmin/+ mice.
• Mechanisms of tumor angiogenesis and radiosenstization.

Recent Representative Publications

Leeper DB, Engin K, Wang J & Li DJ (1998) Effect of I.V. glucose vs combined I.V. glucose plus oral glucose on human tumor extracellular pH for potential sensitization to thermoradiotherapy. Int. J. Hyperthermia 14:257-269.

Owen CS, Wahl ML, Pooler PM, Coss RA and Leeper DB (1998) Temporal association between alterations in proton extrusion and low pH adaptation. Int. J. Hyperthermia 14:227-232.

Waterman FM, Komarnicky LT & Leeper DB (1998) Changes in human tumor blood flow and pH during fractionated course of thermoradiotherapy. Int. J. Hyperthermia 14:421-434.

Biaglow JE, Manevich Y, Leeper DB et al. (1998) MIBG inhibits respiration: Potential for radio- and hyperthermeic sensitization. Int. J. Radiat. Oncol. Biol. Phys. 42:871-876.

Leeper DB, Engin K, Wang J & Li DJ (1998) Effect of I.V. glucose vs combined I.V. glucose plus oral glucose on human tumor extracellular pH for potential sensitization to thermoradiotherapy. Int. J. Hyperthermia 14:257-269.

Wahl ML, Pooler PM, Briand P, Leeper DB & Owen CS (2000) Intracellular pH regulation as a function of extracellular pH in a human premalignant and malignant breast cancer cell line. J. Cell Physiol. 183:373-380.

Dicker AP, Lin C-C & Leeper DB (2000) Isotope selection for permanent prostate implants? An evaluation of 103Pd vesus 125I based on radiobiological effectiveness and dosimetry. Sem. Urol. Oncol. 18:152-159.

Zhou R, Leeper DB & Glickson JD (2000) Intracellular acidification of human melanoma xenografts by the respiratory inhibitor m-iodobenzylguanidine plus hyperglycemia: A 31P magnetic resonance spectroscopy study. Cancer Res. 60:3532-3536.

Burd R, Wachsberger PR, Biaglow JE, Wahl ML, Lee I & Leeper DB (2001) Absence of Crabtree effect in human melanoma cells adapted to growth at low pH: reversal by respiratory inhibitors. Cancer Res. 61:5630-5635.

Wang YS, Guan J, Wang HY, Wang Y, Leeper, DB & Iliakis G. (2001) Regulation of DNA replication after heat shock by replication protein A-nucleolin interactions. J. Biol. Chem. 276: 20579-88.

Zhou R, Bansal N, Leeper DB, Pickup S & Glickson JD (2001) Enhancement of hyperglycemia-induced acidification of human melanoma xenografts with inhibitors of respiration and ion transport. Acad Radiol. 8:571-82.

Wachsberger PR, Gressen EL, Bhala A, Bobyock SB, Storck C, Coss RA, Berd D & Leeper DB (2001) Variability in glucose transporter-1 levels and hexokinase activity in human melanoma. Melanoma Res., 11:1-9.

Wahl ML, Owen JA, Burd R, Heralds RA, Nogami SS, Rodeck U, Berd D, Leeper DB & Owen CS (2002) Regulation of intracellular pH in human melanoma: Potential therapeutic implications. Molec. Cancer Therap. 1:617-28.

Lee I, Glickson, JD, Dewhirst MW, Leeper DB, Burd R, Poptani H, Nadal L, McKenna WG, and Biaglow JE (2002) Effect of glucose  meta-iodobenzylguanidine (MIBG) on the radiation response of R3230 AC tumors. Ed. J.E. Dunn and A.M. Swartz, Oxygen Transport to Tissues XXII, Pabst Scientific Publishers, Germany, in press.

Wachsberger PR, Burd R, Wahl ML & Leeper DB (2002) Effect of betulinic acid on hyperthermia-induced cell killing in low pH adapted melanoma cells. Int. J. Hyperthermia, 18:153-164.
Guan J, Stavridi E, Leeper DB & Iliakis G (2002) Effects of hyperthermia on p53 protein expression and activity. J. Cell. Physiol. 190:365-374.

Hekmatyar SK, Poptani H, Babsky A, Leeper DB & Bansal N (2002) Noninvasive magnetic resonance thermometry using thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA-) complex. Int. J. Hypertherm. 18:165-179.

Han J-S, Storck CW, Wachsberger PR, Leeper DB, Berd D, Wahl ML & Coss RA (2002) Acute extracellular acidification increases nuclear associated protein levels in human melanoma cells during 42°C hyperthermia and enhances cell killing. Int. J. Hypertherm. 18:404-415.

Wachsberger, PR, Bhala A, Bobyock SB, Wahl ML, Owen CS, Rifat SB & Leeper DB (2002) Quercetin inhibits thermotolerance development in Chinese hamster ovarian carcinoma cells adapted to growth at low pH. Int. J. Hypertherm. (in press).

Burd R, Zalipsky U, Pollard MD, Wachsberger PR, O'Hara MD, Berd D & Leeper DB (2002) Acidification and oxygenation of human melanoma xenografts during exposure to MIBG and hyperglycemia. Radiat. Res. (in press).

Coss RA, Owen CS, Wahl ML, Storck CS, Bobyock SB, Wachsberger PR & Leeper DB (2002) Acute acidification differentially inhibits 42°C-induction of Hsp27 and Hsp70 in human melanoma cells adapted to growth at low pH. Int. J. Hypertherm. (in press).

Back to Department Faculty