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NIH Grant Explores Stem Cell Regeneration Following Radiation Exposure

Chandan Guha, MD, Vice Chairman and Professor of Radiation Oncology and Pathology at Montefiore and Albert Einstein College of Medicine, received a five-year, $10.8 million National Institutes of Health grant to develop stem-cell based therapies to treat radiation-induced toxicity and prevent death in patients. The research project, conducted in partnership with Einstein, is part of a larger national homeland security initiative focused on developing radiation countermeasures. The grant is supported by the National Institute of Allergy and Infectious Diseases, and Einstein is one of seven Centers for Medical Countermeasures Against Radiation in the country. The study could have vast clinical implications for patients and military personnel.

Two years ago, Dr. Guha discovered that injecting an intestinal stem cell growth factor protein called R-spondin1 into mice protected them from lethal doses of radiation. Now, Dr. Guha and colleagues will investigate R-spondin1, which spurs intestinal stem cell regeneration, examine what other types of proteins may also have this capability and then elucidate the biological mechanisms. This research could lead to small molecule drugs that increase the therapeutic effects of cancer treatment while protecting against toxic side effects-benefiting cancer patients, as well as people exposed to radiation from nuclear energy plant disasters and military personnel and first responders exposed to terrorist attacks that involve radiation. Currently, radiation toxicity is treated by transplanting bone marrow, which is not always effective.

"Low to moderate doses of radiation therapy delivered to the whole body or abdomen kill intestinal stem cells, causing the intestine to break down irreparably," said Dr. Guha. "As a result, radiation doses for abdominal cancers are kept very low to prevent a serious illness called Radiation-Induced Gastrointestinal Syndrome. Developing a new stem cell therapy that protects against intestinal injury opens up the possibility of increasing the doses of radiation and improving treatment for abdominal cancers."