The threat of radiological attacks has grown in recent years, warranting a concerted effort to translate the molecular advances of radiation research into bona fide medical products. These medical products must be directed toward the identification and treatment of attack victims who have received a radiation exposure in a critical dose range (approximately 2Gy to 8Gy). Left untreated, these victims die from complications of bone marrow failure. The purpose of the program is to (1) develop, test, and calibrate a biodosimeter to detect total body irradiation exposure in this critical range and (2) develop and test novel radioprotective agents to treat the bone marrow toxicity, and Gl toxicity, of radiation victims. To accomplish this goal, we have assembled four leading basic science investigators from related fields. Project 1 (Alan D'Andrea) will calibrate a biodosimeter and screen novel radioprotective drugs. . Project 2 (Stephen Elledge) will use shRNA libraries to identify targets in radiation response pathways. Project 3 (Peter Sicinski) will employ novel genetic mouse models to study the role of cell cycle control in radiation sensitivity and resistance. The program is fortified by the establishment of two unique core facilities (the Mouse Biology and Stem Cell Core, and the Institute of Chemistry and Chemical Biology Core). We have also created a novel Clinician-Scientist Training Program in order to develop the careers of young investigators in this area, and a Pilot Grant Program, to take advantage of the unique opportunities in Boston and to allow rapid redirection of resources, as needed. The program is designed to accelerate the development of new medical applications in the field of countermeasures against radiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI067751-05
Application #
7680295
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (O1))
Program Officer
Ramakrishnan, Narayani
Project Start
2005-08-31
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2011-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$1,860,332
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Beemelmanns, Christine; Ramadhar, Timothy R; Kim, Ki Hyun et al. (2017) Macrotermycins A-D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39. Org Lett 19:1000-1003
Guinan, Eva C; Palmer, Christine D; Mancuso, Christy J et al. (2014) Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin. Innate Immun 20:697-711
Guinan, Eva C; Barbon, Christine M; Kalish, Leslie A et al. (2011) Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death. Sci Transl Med 3:110ra118
D'Andrea, Alan D (2010) Susceptibility pathways in Fanconi's anemia and breast cancer. N Engl J Med 362:1909-19
Parmar, Kalindi; Kim, Jungmin; Sykes, Stephen M et al. (2010) Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1. Stem Cells 28:1186-95
Tolopko, Andrew N; Sullivan, John P; Erickson, Sean D et al. (2010) Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities. BMC Bioinformatics 11:260
Parmar, Kalindi; D'Andrea, Alan; Niedernhofer, Laura J (2009) Mouse models of Fanconi anemia. Mutat Res 668:133-40
Sun, Yingli; Jiang, Xiaofeng; Xu, Ye et al. (2009) Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat Cell Biol 11:1376-82
Moldovan, George-Lucian; D'Andrea, Alan D (2009) FANCD2 hurdles the DNA interstrand crosslink. Cell 139:1222-4
Kim, Jung Min; Parmar, Kalindi; Huang, Min et al. (2009) Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Dev Cell 16:314-20

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