The University of Rochester Medical Center once again has received federal bioterrorism funding, allowing investigators to build on several new discoveries made during the past five years to improve our ability to treat radiation injury, especially from an act of terrorism.
The URMC was awarded an initial grant of $21 million in 2005 to become part of a national research network, Centers for Medical Countermeasures Against Radiation. The Centers were charged with researching how best to respond to a possible dirty bomb or other radiological or nuclear attack. A second, $15 million, five-year award, received August 1, 2010, from the National Institutes of Health/National Institute of Allergy and Infectious Disease, will allow URMC researchers to focus on testing known drugs and experimental agents – particular antibiotics, antioxidants, and anti-inflammatories including the Asian and Indian folk medicine, curcumin – and their ability to ward off systemic radiation injury that affects the lungs, brain, skin, and bone marrow.
Principal Investigator Jacqueline P. Williams, Ph.D., research professor in the Department of Radiation Oncology, said the new project places the URMC firmly in a leadership position in the counterterrorism effort.
“For decades we have built an expertise here in looking at the delayed effects of radiation exposure, mostly in the context of cancer treatment, and now we are able to apply that knowledge to the terrorism scenario,” Williams said. “The most exciting part of this project is that through these and other collaborative efforts, we believe we are at the brink of discovering ways to mitigate the damage caused by radiation and protect the body from the repercussions that can arise months or years after the exposure.”
Previous research has revealed that it’s not just the immediate effect of radiation that makes adults and children sick, Williams said. Rather, the radiation damage can remain relatively undetected in key tissues and organs, but will trigger life-threatening illnesses after an injury that occurs later. The catalyst can be as benign as the flu or a small wound on the skin, she said, and this is particularly worrisome in children. The URMC is one of the only groups looking at this population.
Cancer patients will also benefit from the bioterrorism project, as researchers uncover new information about how to reduce side effects such as a loss of brain function that can result from chemo and radiation therapy, or how to protect the blood vessels and bone marrow from radiation injury. The URMC investigators will be working closely with industry partners such as ImmuneRegen Biosciences of Scottsdale, Arizona, and Navigen, of Salt Lake City, Utah, to test emerging drugs in this area.
“Most of the known drugs and experimental agents that we are testing have the potential to reduce the side effects of cancer treatment without adding new toxicities,” Williams said.
The URMC’s research is divided into four main projects, with each group collaborating on data analysis, tissue samples and models:
- Project 1, lung injury. The objective is to better understand how the lung responds to radiation in a scenario in which the lungs are not the only organs suffering damage. For example, if the blood or bone marrow cells were damaged by exposure, and therefore these cells could not be recruited to the lung, how would that impact a person’s recovery? A new drug under development to treat lung fibrosis that targets damage to the blood vessels will be tested in this project.
- Project 2, brain injury. The cognitive deficits associated with radiation injury to the brain are well known, although the precise causes are unclear. Researchers are planning to assess drugs that inhibit inflammation in the brain and restore function. They plan to test a well-tolerated antibiotic that crosses the blood-brain barrier, as well as a series of newly developed antioxidants.
- Project 3, skin injury. The skin is vital in providing a barrier against radiation. In the previous funding cycle, the URMC made important strides in deciphering the mechanisms, such as dendritic cell depletion, involved in skin injury. Researchers aim to better understand how skin and immune function are affected by exposure, and whether three experimental drugs, including a topical agent derived from curcumin, which gives the spice turmeric its yellow color, might reverse damage.
- Project 4, injury to the blood-forming system. Researchers believe that both external radiation exposure and internal exposure, due to inhalation and/or ingestion of radioactive particles, can cause severe and lasting damage to blood stem cells. They will test antioxidants and a new drug under development that purportedly stabilizes and repairs blood vessels.
In addition to Williams, other investigators are: Jacob Finkelstein, Ph.D., professor in the departments of Pediatrics, Environmental Medicine and Radiation Oncology; M. Kerry O’Banion, M.D., Ph.D., professor of Neurobiology and Anatomy; John A. Olschowka, Ph.D., associate professor of Neurobiology and Anatomy; Edith M. Lord., Ph.D., professor of Microbiology and Immunology and Cancer; Julie Ryan, Ph.D., M.P.H., assistant professor of Dermatology and Radiation Oncology; James Palis, M.D., professor of Pediatrics, Cancer and Biomedical Genetics; Laura M. Calvi, M.D., associate professor of Medicine; Bruce M. Fenton, Ph.D., professor of Radiation Oncology; and Yuhchyau Chen, M.D., Ph.D., interim chair, Department of Radiation Oncology.
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