NIH R01: CCRP Initiative: Chemical Threat Agent-induced Pulmonary and Ocular Pathophysiological Mechanisms

Funding Opportunity Number: RFA-ES-24-005

Deadline: September 24, 2024

Objectives

Almost 200 Chemicals of Concern (CoC) have been identified by the U.S. Department of Homeland Security (DHS) as high consequence public health threats. There is an urgent unmet need to gain a clear understanding of the physiological mechanisms involved in the initiation and downstream events of injury from acute exposure to these chemicals.

CoCs are organized within toxidromes established by the U.S. Government. Toxidromes group chemicals based on their primary modes of toxicity. One benefit of this approach is that a single MCM may be effective against multiple different CoCs. To find out whether your toxicant is of interest to the CCRP, please contact the scientific program contact listed in this NOFO.

This NOFO is intended to encourage health scientists to pursue studies using diverse animal models, organoid tissues, ex vivo studies using human or animal tissues, in vitro cell culture systems, and/or in silico models.

This NOFO intends to support fundamental research that will characterize the acute and/or long-term pathophysiological effects, such as cellular, biochemical, and molecular mediators/pathways, after CoC exposure to pulmonary and/or ocular toxicants. Projects seeking to understand the impact on diverse comorbidity factors such as age, sex, pregnancy, and/or pre-existing disease conditions, are encouraged.

Specific topics of research interest include, but are not limited to, the following:

Pulmonary Toxicant Research Topics of Interest: CoCs of pulmonary interest include, but are not limited to, those that induce pulmonary edema, pneumonitis, and fibrosis, such as chlorine, phosgene, sulfur mustard, nitrogen mustard, and oleum.

Given the above, pulmonary applications are encouraged to consider the following aspects:

  • Studies proposing to use in vitro models should include at minimum one cell culture model with at least two different cell types relevant to the target organ, and two or more toxicants and multiple time points post exposure. Applications using only immortalized/transformed cell lines or only one toxicant will be considered not responsive.
  • Applications using animal models should use at least two different species or strains and both sexes, or collaborative cross strains or knock out models and both sexes, and a minimum of two toxicants as well as multiple time points post exposure to gain comparative understanding of the toxic effects. Applications using only one sex or one species/strain or one toxicant are not responsive.
  • Studies investigating the role of susceptibility in the manifestation of toxic effects should use neonate, adult, old/aged animals of both sexes and assays performed at multiple time points post exposure and a minimum of two toxicants. Applications using only one sex or one susceptibility condition or one toxicant will be considered not responsive.
  • Studies proposing to use high throughput screening approaches such as organoid tissue systems should use more than two toxicants and multiple time points post exposure that will facilitate cross comparison analysis for identifying common molecular targets.
  • Applications that use a combination of in vitro, ex vivo or in vivo studies should use a minimum of two toxicants and both sexes with data generated at multiple time points post exposure.
  • Applications using only one sex or one toxicant or one time point are considered not responsive.
  • Applications using in silico and computational predictive modeling approaches for acute lung injury mechanisms are also encouraged.
  • Studies to investigate delayed effects of acute toxicant exposure are encouraged to include acute response studies in two species/strains and both sexes, and to provide a strong justification for selection of one strain or one sex for investigations focused on delayed responses. The delayed response studies should include a time point of at the least 45 days.
  • Applications investigating chronic/repetitive exposures are not responsive to this NOFO.

For more information, please see the opportunity webpage.