Key Dates

Related Announcements

NOT-GM-20-046 - Notice of NIGMS Participation in NOT-ES-20-018

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-185 - Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-184 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

Issued by

National Institute of Environmental Health Sciences (NIEHS)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Purpose

The purpose of this Notice of Special Interest (NOSI) is to inform potential applicants that the National Institute of Environmental Health Sciences (NIEHS), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have special interest in applications to investigate the mechanisms controlling the resolution of inflammation in chronic disease states.

Background

Inflammation is a critical, acute, and protective biological response to infection, injury, or environmental exposures; however, excessive, uncontrolled, and prolonged inflammatory states can lead to collateral damage to tissues and organs and is being recognized as a major contributor to the morbidity of chronic diseases. Over the past decade, research efforts led to the identification of endogenous pathways that facilitate the resolution of inflammation presenting novel opportunities to expand our knowledge on the potential role of perturbations in these endogenous resolution pathways in the development of chronic inflammation. Additionally, gaining a comprehensive understanding of the intersections of competing resolution and proinflammatory pathways could lead to new opportunities for therapeutic and intervention strategies to promote the resolution of inflammation and reduce the intensity, duration, and ultimately the development of chronic inflammation.

To assess the current state of the science in the field of inflammation resolution biology, a trans-NIH workshop was organized at the NIEHS (https://factor.niehs.nih.gov/2019/5/science-highlights/inflammation/index.htm). The participants of the workshop recognized the need to expand our fundamental understanding of resolution pathways and to assess the applicability in promoting resolution as a therapeutic/ intervention strategy to reduce the morbidity associated with diverse chronic inflammatory diseases. As an initial step, the participating NIH Institutes and Centers are seeking grant applications focused on comprehensive molecular, biochemical, and physiological characterization of diverse players, pathways, and genetic and epigenetic regulation of the molecular pathways promoting the resolution of chronic inflammatory states.

Research Objectives

This Trans-NIH partnership seeks to support research to gain comprehensive understanding of the biology of the resolution of inflammation to elucidate the critical distinctions between resolution and anti-inflammatory mechanisms.

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

• Identification and molecular and cellular characterization of resolution mediators, their tissue and species specificity, and the downstream phenotypic effects on the transformation of immune cells from pro- to anti-inflammatory states;
• Development and/or use of disease animal models to characterize the relationship between dysregulated resolution resulting from acute inflammation and development of a chronic inflammatory status;
• Understanding the role of genetic and other susceptibility factors such as environmental exposures and nutritional deficiencies in failed or dysregulated inflammation resolution pathways in diverse chronic inflammatory disease conditions such as ageing, asthma, cancer, obesity, diabetes, etc.; and
• Comprehensive screening efforts for identification of novel therapeutic targets in key resolution pathways and explore their physiology and pharmacology.

Within this broad category of topics, each participating Institute has a specialized focus of interest as outlined below:

NIEHS:

A vast literature knowledge base implicates induction of an acute inflammatory response following exposure to a diverse array of environmental and occupational chemicals. The resolution of this acute inflammatory response may be delayed or perturbed due to factors such as age, gender, and preexisting disease state. We are also beginning to understand that some environmental agents (e.g., air pollutants) induce chronic systemic inflammation. Greater understanding of the contribution of compromised resolution of inflammation to chronic exposure-induced systemic inflammation may aid in developing preventive and interventional strategies to address environmental morbidity issues.

This NOSI encourages, but is not limited to, research applications in the following areas:

• Characterization of exposure-induced inflammation resolution kinetics, cell and tissue specificity.
• Molecular characterization of cell and tissue specific resolution phenotype in normal and disease models and the impact of exposure to environmental agents
• Understanding the impact of gender, age and disease on exposure-induced inflammation resolution
• Characterization of cardiopulmonary inflammation resolution phenotype using collaborative cross and other rodent models
• Generation of targeted genetic and epigenetic profiles of genes involved in the inflammation resolution pathways
• Role of macrophage heterogeneity in acute versus chronic inflammation and their role in inflammation resolution
• Comprehensive characterization of macrophage differentiation in the evolution of chronic inflammation and the role of inflammation resolution pathways

Research on identifying exposure-induced inflammatory mechanisms is considered non-responsive to this initiative.

NHLBI:

Investigations into the factors and molecular mechanisms that are essential to enhance/promote inflammation resolution are considered to be responsive to this notice. Research on identifying the role of inhibitors of inflammation or anti-inflammatory agents is not considered to be responsive to this announcement. This NOSI encourages, but is not limited to, research applications in the following areas:

• What are the biosynthesis and functions of the specialized pro-resolution mediators (SPMs) in HLBS diseases? How do SPMs and activation of resolution programs contribute to the resilience of host during inflammation?
• What are the intervention strategies using pro-resolving lipid mediators for promoting therapeutic resolution of inflammation in the context of COPD, asthma, e-Cigarettes, acute lung disease, vascular disease, and heart failure?
• What is the underpinning mechanism regulating proteins (such as annexin A1 and secretory leukocyte protease inhibitor) and peptides (such as annexin-, melanocortin- and chemerin-derived peptides) that activate inflammation resolution program?
• What are the molecular pathways driving efferocytosis-directed inflammation resolution in HLBS diseases or HLB transplant tolerance?
• What is the role of genetic and epigenetic regulators in inflammation resolution, and how could this knowledge be used for developing new therapeutics or interventional strategies against various HLBS disorders?
• What is the role of inflammation resolution in preventing deep vein thrombosis (DVT) and post thrombotic syndrome (PTS)?
• What are the blood biomarkers to assess the resolution post bacterial and viral inflammation?

NIAMS:

Uncontrolled and dysfunctional resolution of inflammation can lead to chronic inflammation, a common pathogenic element among diseases within the NIAMS core mission. Therefore, unraveling basic, translational, and pre-clinical mechanisms of inflammation resolution would contribute significantly to the understanding of pathogenesis and the development of innovative therapies for chronic inflammatory diseases within the NIAMS mission.

This NOSI encourages, but is not limited to, research applications in the following areas:

• Study of the mechanistic role of novel or well-known inflammation resolution mediators in the pathogenesis of NIAMS diseases.
• Study of dynamics of biosynthesis of inflammation resolution mediators and its correlation with clinical manifestations of NIAMS diseases.
• Study of functional genetic, genomic or epigenetic landscapes related to inflammation resolution mechanisms in NIAMS diseases.
• Integration of multi-omics such as peptide and protein profiling, and lipidomics with systems biology to identify inflammation resolution mediators as diagnostic or prognostic biomarkers, and further therapeutic targets for NIAMS diseases.
• Study of impact of sex, gender, age, biopsychosocial or behavioral disparity on mechanisms of inflammation resolution in NIAMS diseases.
• Development of animal or organoid models to understand molecular, cellular, and tissue-specific mechanisms of inflammation resolution, further development as screening and validation platform for therapies to improve NIAMS diseases.

Application and Submission Information

Applicants must select the IC and associated FOA to use for submission of an application in response to this NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that FOA. Non-responsive applications will be withdrawn from consideration for this initiative. In addition, applicants using NIH Parent Announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those FOAs are acceptable and based on usual application-IC assignment practices.

This NOSI applies to due dates on or after October 1, 2020 and subsequent receipt dates through May 31, 2024.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice.

NIEHS will accept applications submitted under PA-20-195, PA-20-185, PA-20-184, and PA-20-196.

NHLBI will accept applications submitted under PA-20-183 and PA-20-185. Support of mechanistic clinical trials will be allowed. For mechanistic clinical trial submissions, refer to NOT-HL-18-611: NHLBI Policy Regarding Submission of Clinical Trial Applications.

NIAMS will accept applications submitted under PA-20-195 and PA-20-185.

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-ES-20-018 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Inquiries

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed funding opportunity announcements.

Scientific/Research Contact(s)

Srikanth’s Nadadur, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3296
Email: [email protected]

Guofei Zhou, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-7825
Email: [email protected]

Heiyoung Park, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: [email protected]