In many human conditions (e.g. inflammatory bowel disease, sepsis, multi-organ injury and failure), the progression from acute inflammatory insult to either resolution or chronicity remains impossible to predict. Our recent findings indicate that resolution of local inflammation involves active resolution circuits that generate a novel genus of potent Specialized Pro-Resolving Mediators (SPM). SPM are comprised of distinct structural families of lipid mediators (LM) including resolvins, protectins and maresins derived from essential omega-3 fatty acids. Novel SPM that are potent anti-inflammatories also stimulate uptake of apoptotic neutrophils, microbial containment and their clearance by phagocytes and mucosal epithelia. These findings reveal an urgent clinical need to navigate resolution to establish fundamental mechanisms in resolution pharmacology. To address this health mission, a multidisciplinary team of experts is assembled in this program project that will use a systematic approach to elucidate cellular and molecular mechanisms in self-limited experimental systems. Our team and overall project is focused on elucidating programmed resolution of acute inflammation with an emphasis on LM, SPM and resolution pharmacology for new treatments. Ongoing studies give rise to an overarching hypothesis tested by four highly complementary integrated projects with synergistic approaches. The overall novel hypothesis addressed is: Resolvins, protectins and maresins constitute a new genus of SPM that temporally regulate endogenous anti inflammatory and pro-resolving pathways. SPM govern resolution via regulated leukocyte responses, enhanced mucosal defense and bacterial containment these molecular events can be harnessed for novel resolution pharmacology to treat diseases. This P01 team consists of 4 projects, 2 scientific cores and an advisory unit focused on establishing LM-resolution metabolome, stereo-controlled synthesis of SPM and their specific mechanisms in resolution, anti-inflammatory and clearance pathways. Selected synthetic SPM will be scaled-up for demonstration of their unique mode of action in vivo in a resolution pharmacology core using experimental disease models. Our broad goal is to bring forth new treatments in resolution.

Public Health Relevance

To improve patient care, a goal of this program project is to harness new specialized pro-resolving mediators (SPM) and resolution pharmacology as a new therapeutic approach to better treat human diseases and tissue injury where resolving local inflammation is important. The potential for resolution pharmacology in new treatments could diminish the healthcare burden of inflammatory diseases.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1-PPBC-3 (CP))
Program Officer
Okita, Richard T
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Sorokin, Alexander V; Norris, Paul C; English, Justin T et al. (2018) Identification of proresolving and inflammatory lipid mediators in human psoriasis. J Clin Lipidol 12:1047-1060
Serhan, Charles N; Chiang, Nan; Dalli, Jesmond (2018) New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration. Mol Aspects Med 64:1-17
Dalli, Jesmond; Colas, Romain A; Walker, Mary E et al. (2018) Lipid Mediator Metabolomics Via LC-MS/MS Profiling and Analysis. Methods Mol Biol 1730:59-72
Lahvic, Jamie L; Ammerman, Michelle; Li, Pulin et al. (2018) Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132. Proc Natl Acad Sci U S A 115:9252-9257
Serhan, Charles N; Levy, Bruce D (2018) Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest 128:2657-2669
Motwani, Madhur P; Colas, Romain A; George, Marc J et al. (2018) Pro-resolving mediators promote resolution in a human skin model of UV-killed Escherichia coli-driven acute inflammation. JCI Insight 3:
Gromovsky, Anthony D; Schugar, Rebecca C; Brown, Amanda L et al. (2018) ?-5 Fatty Acid Desaturase FADS1 Impacts Metabolic Disease by Balancing Proinflammatory and Proresolving Lipid Mediators. Arterioscler Thromb Vasc Biol 38:218-231
Halade, Ganesh V; Norris, Paul C; Kain, Vasundhara et al. (2018) Splenic leukocytes define the resolution of inflammation in heart failure. Sci Signal 11:
de la Rosa, Xavier; Norris, Paul C; Chiang, Nan et al. (2018) Identification and Complete Stereochemical Assignments of the New Resolvin Conjugates in Tissue Regeneration in Human Tissues that Stimulate Proresolving Phagocyte Functions and Tissue Regeneration. Am J Pathol 188:950-966
Hellmann, Jason; Sansbury, Brian E; Wong, Blenda et al. (2018) Biosynthesis of D-Series Resolvins in Skin Provides Insights into their Role in Tissue Repair. J Invest Dermatol 138:2051-2060

Showing the most recent 10 out of 165 publications