P01AI165380

Multi-Scale Evaluation and Mitigation of Toxicities Following Internal Radionuclide Contamination - Overall: Abstract

History has taught us that exposures to radionuclides can happen any day, almost anywhere in the US and elsewhere, and we have done little to prepare ourselves. Our ability to perform dosimetry modeling for such scenarios and efforts into biomarker and mitigation discovery are archaic, and our tendency to rely on external beam radiation to model these is utterly misplaced. We should and we can do much better.

This program centers on the hypothesis that radiation from internal emitters is very unevenly distributed within a body, amongst organs, and even within organs, tissues, and cells. The half-life and decay schema of the radionuclide, its activity and concentration, particle size and morphology, and its chemical form and solubility are all critical, as are the route of uptake, tissue structure, genetic makeup, physiology, danger signaling, and the crosstalk with the immune system.

Conceptually, this suggests that the analysis of radionuclide distribution requires measurements at the meso, micro, and nano level for accurate dosimetry modeling and biokinetics analyses that will much better align with biological endpoints and, therefore, with meaningful countermeasure development. In many ways, our program integrates the three main pillars of radiation science, namely radiation physics, radiation chemistry, and radiation biology, taking into account pharmacokinetics and pharmacodynamics aspects of particle distribution at subcellular, cellular, and tissue levels.

In other words, to understand the biological effects of internal emitters and find the best possible mitigation strategies, a systematic study is called for, one that includes but is not limited to:

A) Radionuclide physical and chemical form and intravital migration,
B) Protracted exposure times,
C) Radiation quality parameters,
D) Novel virtual phantom modeling beyond few macro reference models,
E) Novel biokinetics with sex- and age-specificity,
F) Meso, micro, and nano scale histology and immunohistochemistry with integrated radionuclide distribution information,
G) Exploration of molecular biomarkers of radionuclide intake and contamination, and
H) Countermeasures that modulate radionuclide distribution and possibly also improve DNA, cell, and tissue repair.

We have assembled a team with diverse scientific expertise that can tackle these challenges within an integrated program. There is an incredibly impressive technological toolbox at our disposal, and our goal is to generate a meaningful blueprint for understanding and predicting the biological consequences of exposure to radionuclides. The possible benefits of this program to the radiation research community and the general population are immense.

Northwestern University

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.

93.855 - Allergy and Infectious Diseases Research

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

Illinois United States

State-Wide

NIAID Investigator Initiated Program Project Applications (P01 Clinical Trial Not Allowed) (PAR-20-072)

Amendment Since initial award the End Date has been shortened from 02/28/27 to 02/28/25 and the total obligations have increased 286% from $2,246,717 to $8,680,319.