P01AI186817

MITIGATOR EFFICACIES AFTER REALISTIC IMPROVISED NUCLEAR DEVICE (IND) EXPOSURE: MERIE - THE NEED FOR IMPROVED RADIATION EFFECT MITIGATORS STEMS FROM THE SIGNIFICANT PROBABILITY OF THE DETONATION OF AN IMPROVISED NUCLEAR DEVICE (IND). TYPICALLY PHARMACEUTICAL RADIATION COUNTERMEASURES HAVE BEEN TESTED AGAINST X RAYS DELIVERED OVER A FEW MINUTES. IN PRACTICE, HOWEVER, 1) THE MAJORITY OF THE IND-RELATED RADIATION DOSE WILL BE DELIVERED BY “DIRECT” RADIATION FROM THE IND, OVER A TIME PERIOD OF LESS THAN A MICROSECOND, AND 2) A SIGNIFICANT COMPONENT (10 - 50%) OF THE BIOLOGICAL EFFECT FROM A GROUND-BURST IND WILL BE FROM FISSION NEUTRONS. THE BIOLOGICAL EFFECTS AND ASSOCIATED MECHANISMS FROM THESE IND-SPECIFIC RADIATIONS ARE TYPICALLY QUITE DIFFERENT AS COMPARED WITH THE CORRESPONDING EFFECTS AND MECHANISMS ASSOCIATED WITH CONVENTIONAL X RAYS DELIVERED OVER A FEW MINUTES. IN ADDITION THERE IS EVIDENCE THAT MITIGATOR PERFORMANCE IS DIFFERENT FOR THESE IND- SPECIFIC RADIATION TYPES. IT IS THEREFORE IMPORTANT TO UNDERSTAND WHETHER RADIATION COUNTERMEASURES THAT HAVE BEEN DEVELOPED AND TESTED AGAINST X RAYS DELIVERED OVER TIME PERIODS OF A FEW MINUTES WILL ALSO BE EFFECTIVE IN THESE MORE REALISTIC IND EXPOSURE SCENARIOS. AT COLUMBIA UNIVERSITY UNIQUE RADIATION SOURCES ARE AVAILABLE TO SIMULATE EACH OF THESE IND-SPECIFIC EXPOSURES. THESE TOOLS WILL ALLOW EACH OF THE RESEARCH PROJECTS TO ADDRESS THE SAME COMMON RESEARCH THEMES: 1. ARE RADIATION MITIGATORS THAT WERE DEVELOPED AND TESTED WITH X RAYS IRRADIATED OVER A FEW MINUTES, ALSO EFFECTIVE AGAINST A) VERY SHORT, VERY HIGH DOSE RATE RADIATION EXPOSURES, B) IND-SPECIFIC NEUTRONS? 2. USING THESE REALISTIC IND EXPOSURES, CAN MITIGATORS DEVELOPED FOR SPECIFIC ENDPOINTS HAVE UTILITY FOR OTHER KEY RADIOBIOLOGICAL ENDPOINTS? 3. USING THESE REALISTIC IND EXPOSURES, CAN COMBINING MULTIPLE MITIGATORS THAT WERE EACH DESIGNED FOR SPECIFIC ENDPOINTS, HAVE INCREASED OVERALL UTILITY IF GIVEN IN COMBINATION (“POLYPHARMACY”)? IN THIS HIGHLY SYNERGISTIC PROPOSAL, THE PROJECTS AND CORES ARE TIGHTLY LINKED BY COMMON RESEARCH THEMES AND HYPOTHESES, BY A SHARED ANIMAL MODEL, AND BY SHARED SAMPLES AND DATA. THE WAG/RIJCMCR RATS THAT WILL BE USED SEQUENTIALLY MANIFEST OUR RADIATION ENDPOINTS OF INTEREST, ALLOWING THE SEQUENTIAL STUDY IN THE SAME IRRADIATED ANIMALS OF GI-ARS (PROJECT 1), LUNG AND KIDNEY DAMAGE (PROJECT 2) AND CARDIOVASCULAR DAMAGE (PROJECT 3). EACH PROJECT ALSO FEATURES STATE-OF-THE-ART PHARMACEUTICAL MITIGATORS THAT HAVE ALREADY BEEN DESIGNED AND TESTED BY THE RELEVANT PROJECT TEAM, USING CONVENTIONAL X RAYS FOR THEIR RESPECTIVE ENDPOINT. THE PROPOSAL ALSO FEATURES THREE STRONG CENTRAL RESEARCH CORES (RADIATION, BIOMARKER AND STATISTICS), UNIFYING THE RESEARCH PROGRAM. THE 7 PROJECT AND CORE TEAMS ALREADY HAVE A STRONG TRACK RECORD OF WORKING TOGETHER, WITH >260 TEAM-TEAM INTERACTIONS IN PUBLICATIONS, AND >50 TEAM-TEAM INTERACTIONS IN GRANTS - LARGELY FROM NIAID RNCP GRANTS. FINALLY A HIGHLY EXPERIENCED ADMINISTRATIVE CORE WILL PROVIDE FISCAL MANAGEMENT SUPPORT AND WILL ORGANIZE AN ANNUAL 1.5-DAY RETREAT, COUPLED WITH A FULL-DAY TRAINING SESSION TARGETING JUNIOR RADIATION SCIENTISTS.

The Trustees Of Columbia University In The City Of New York

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.310 - Trans-NIH Research Support

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

New York United States

State-Wide

NIAID Investigator Initiated Program Project Applications (P01 Clinical Trial Not Allowed) (PAR-22-225)