Overall Objective
The research activities of the Division of Radiation Health seek to maximize the benefits
and/or minimize the risk associated with exposure to ionizing radiation.
The overall
objectives of our research are 1) to make radiation therapy of cancer safer and more
effective, and 2) to develop effective countermeasures to protect the general population
against radiological and nuclear threats.
Making Radiation Therapy Safer and More Effective
The major goals are to improve the outcome in cancer patients by determining cellular
and molecular mechanisms of radiation-induced side effects and by developing strategies
that minimize short and long-term adverse effects after radiation therapy.
Our current focus is on intestinal and cardiac radiation responses:
Intestine
One line of study investigates the role of endothelial cell dysfunction in the mechanisms
underlying intestinal radiation injury. Another line of study investigates how interactions
between the enteric nervous system and cells of the mucosal immune system regulate
the intestinal radiation response.
Recent publications
Wang J, Zheng H, Kulkarni A, Ou X, Hauer-Jensen M: Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves. Int J Radiat Oncol Biol Phys 2006;64:1528-1536. PMID:16580503
Wang J, Qiu X, Kulkarni A, Hauer-Jensen M: Calcitonin gene-related peptide and substance P regulate the intestinal radiation response. Clin Cancer Res 2006;12:4112-4118. PMID:16818712
Wang J, Boerma M, Fu Q, Fink LM, Hauer-Jensen M: Simvastatin ameliorates radiation enteropathy development after localized, fractionated irradiation by a protein C-independent mechanism. Int J Radiat Oncol Biol Phys 2007;68:1483-1490. PMID:17674978
Boerma M, Wang J, Burnett AF, Santin AD, Roman JJ, Hauer-Jensen M: Local administration of interleukin-11 ameliorates intestinal radiation injury. Cancer Res 2007;67:9501-9506. PMID:17909060
Fu Q, Wang J,Boerma M, Berbee M, Qiu X, Fink LM, Hauer-Jensen M: Involvement of heat shock factor 1 in statin-induced transcriptional upregulation of endothelial thrombomodulin. Circ Res 2008;103:369-377. PMID:18599869
Heart
These experiments use molecular, cellular, functional, and structural techniques to study the role of
immune cells, the endothelin system, transforming growth factor beta, and oxidative stress in the
mechanisms of radiation-induced heart disease.
Recent publications
Boerma M, Wang J, Wondergem J, Joseph J, Qiu X, Kennedy RH, Hauer-Jensen M: Influence of mast cells on structural and functional manifestations of radiation-induced heart disease. Cancer Res 2005;65:3100-3107. PMID:15833839
Boerma M, Wang J, Kulkarni A, Roberto KA, Qiu X, Kennedy RH, Hauer-Jensen M: Influence of endothelin-1 receptor inhibition on functional, structural and molecular changes in the rat heart after irradiation. Radiat Res 2008;170:275-283. PMID:18763854
Boerma M, Roberto KA, Hauer-Jensen M: Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol. Int J Radiat Oncol Biol Phys 2008;72:170-177. PMID:18632215
Radiation Countermeasures Program
The major goal of this program is to provide highly effective, non-toxic pharmaceutical countermeasures
against radiological and nuclear threats. Current emphasis is on HMG-CoA reductase inhibitors,
somatostatin analogs, phosphodiesterase inhibitors, and cytokines.
Recent publications
Ross, CC, MacLeod SL, Plaxco JR, Froud JW, Fink LM, Wang J, Stites WE, Hauer-Jensen M: Inactivation of thrombomodulin by ionizing radiation in a cell-free system: possible implications for radiation responses in vascular endothelium. Radiat Res 2008;169:408-416. PMID:18363428
Kumar KS, Ghosh SP, Hauer-Jensen M: Gamma-Tocotrienol: Potential as a Countermeasure against Radiological Threat. In: Tocotrienols – Vitamin E beyond Tocopherols. Ed. Watson RR, Preedy VR. CRC Press, Boca Raton, FL, 2008, pp. 379-398.
Radiation Combined Injury (RCI)
Up to 70% of casualties in a nuclear incident sustain radiation combined injury (radiation injury combined
with burns, blast injury, penetrating or blunt trauma, or shock, sepsis, or reperfusion injury).
Our expertise in basic and translational normal tissue radiation biology combined with a strong
background
in surgical sciences is particularly conducive to research in this area. Currently, our focus is
on radiation
injury combined with shock/ sepsis or cutaneous injury.
Recent publications
Hauer-Jensen M, Kumar KS, Wang J, Berbee M, Fu Q, Boerma M: Intestinal Toxicity in Radiation- and Combined Injury: Significance, Mechanisms, and Countermeasures. In: Global Terrorism Issues and Developments. Ed. Rene A. Larche. Nova Science Publishers, Hauppauge, NY, 2008, pp. 61-100.
Funding Sources
Research in the Division of Radiation Health has received support from the National Cancer Institute
(NCI),
National Institute of Allergy and Infectious Diseases (NIAID), Defense Threat Reduction Agency
(DTRA),
Department of Veterans Affairs, American Cancer Society, Lance Armstrong Foundation, and the
American Heart Association.
We also have active collaborations with a large number of pharmaceutical and biotechnology companies.
