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
Primdahl, Karoline G; Aursnes, Marius; Walker, Mary E et al. (2016) Synthesis of 13(R)-Hydroxy-7Z,10Z,13R,14E,16Z,19Z Docosapentaenoic Acid (13R-HDPA) and Its Biosynthetic Conversion to the 13-Series Resolvins. J Nat Prod 79:2693-2702
Duvall, Melody G; Levy, Bruce D (2016) DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation. Eur J Pharmacol 785:144-55
Ramon, Sesquile; Dalli, Jesmond; Sanger, Julia M et al. (2016) The Protectin PCTR1 Is Produced by Human M2 Macrophages and Enhances Resolution of Infectious Inflammation. Am J Pathol 186:962-73
Hansen, Trond V; Dalli, Jesmond; Serhan, Charles N (2016) Selective identification of specialized pro-resolving lipid mediators from their biosynthetic double di-oxygenation isomers. RSC Adv 6:28820-28829
Freire, Marcelo O; Dalli, Jesmond; Serhan, Charles N et al. (2016) Neutrophil Resolvin E1 Receptor Expression and Function in Type 2 Diabetes. J Immunol :
Sorokin, Alexander V; Yang, Zhi-Hong; Vaisman, Boris L et al. (2016) Addition of aspirin to a fish oil-rich diet decreases inflammation and atherosclerosis in ApoE-null mice. J Nutr Biochem 35:58-65
Winkler, Jeremy W; Orr, Sarah K; Dalli, Jesmond et al. (2016) Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance. Sci Rep 6:18972
Zhu, Mingqin; Wang, Xiuzhe; Hjorth, Erik et al. (2016) Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis. Mol Neurobiol 53:2733-49
Mayurasakorn, Korapat; Niatsetskaya, Zoya V; Sosunov, Sergey A et al. (2016) DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice. PLoS One 11:e0160870
Dalli, Jesmond; Vlasakov, Iliyan; Riley, Ian R et al. (2016) Maresin conjugates in tissue regeneration biosynthesis enzymes in human macrophages. Proc Natl Acad Sci U S A 113:12232-12237

Showing the most recent 10 out of 125 publications