The main goal of the Drug Translation and Development Core Is to facilitate each scientific project in the development of potential radiation mitigators for various organ systems, including lung (Project 1), CNS (Project 2), skin (Project 3), and bone marrow (Project 4) in the context of a total body radiation exposure. This Core will monitor the progress of testing these agents with respect to the efficacy, safety, toxicology, pharmacokinetics, pharmacodynamics, and quality assurance. As a result, Core D hopes to be able to make recommendations regarding regulatory requirement and, ultimately, will be in a position to recommend strategies towards the development of clinical studies and ultimate drug approval by FDA.

Public Health Relevance

Each Project has candidate agents for radiation mitigation, with several agents being tested across Projects. The drug development process will be focused on pre-clinical development. The formulation of the agents and pre-clinical development in animal models will be centrally recorded and efficacy validated by central statistical analyses (see Biostatistics). The stepwise approach of pre-clinical pharmacology will include demonstration of efficacy in vivo in organs of interest (see all project Research Plans), as well as pharmacokinetics and pharmacodynamic investigations in animal injury models, including combined injury. Candidate agents with promising efficacy and low toxicity in animal models may be considered for clinical development through independent funding.

Agency
National Institute of Health (NIH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI091036-05
Application #
8705382
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
DUNS #
City
Rochester
State
NY
Country
United States
Zip Code
14627
Moravan, Michael J; Olschowka, John A; Williams, Jacqueline P et al. (2016) Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling. J Neuroinflammation 13:30
Groves, Angela M; Johnston, Carl J; Misra, Ravi S et al. (2016) Effects of IL-4 on pulmonary fibrosis and the accumulation and phenotype of macrophage subpopulations following thoracic irradiation. Int J Radiat Biol :1-12
Begolly, Sage; Shrager, Peter G; Olschowka, John A et al. (2016) Fractionation Spares Mice From Radiation-Induced Reductions in Weight Gain But Does Not Prevent Late Oligodendrocyte Lineage Side Effects. Int J Radiat Oncol Biol Phys 96:449-57
Rabender, Christopher; Mezzaroma, Eleonora; Mauro, Adolfo G et al. (2016) IPW-5371 Proves Effective as a Radiation Countermeasure by Mitigating Radiation-Induced Late Effects. Radiat Res 186:478-488
Williams, Jacqueline P; Calvi, Laura; Chakkalakal, Joe V et al. (2016) Addressing the Symptoms or Fixing the Problem? Developing Countermeasures against Normal Tissue Radiation Injury. Radiat Res 186:1-16
Brenner, David J; Chao, Nelson J; Greenberger, Joel S et al. (2015) Are We Ready for a Radiological Terrorist Attack Yet? Report From the Centers for Medical Countermeasures Against Radiation Network. Int J Radiat Oncol Biol Phys 92:504-5
Monin, L; Griffiths, K L; Slight, S et al. (2015) Immune requirements for protective Th17 recall responses to Mycobacterium tuberculosis challenge. Mucosal Immunol 8:1099-109
Monin, Leticia; Griffiths, Kristin L; Lam, Wing Y et al. (2015) Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis. J Clin Invest 125:4699-713
Groves, Angela M; Johnston, Carl J; Misra, Ravi S et al. (2015) Whole-Lung Irradiation Results in Pulmonary Macrophage Alterations that are Subpopulation and Strain Specific. Radiat Res 184:639-49
Evans, Andrew G; Calvi, Laura M (2015) Notch signaling in the malignant bone marrow microenvironment: implications for a niche-based model of oncogenesis. Ann N Y Acad Sci 1335:63-77

Showing the most recent 10 out of 55 publications