CETRI

Serhan Lab

Research in the Serhan laboratory focuses on structural elucidation of bioactive molecules. Dr. Serhan's overall mission is “To identify novel bioactive mediators, pathways, and cellular targets critical in activating resolution of inflammation and their relation to human disease.” Recently Dr. Serhan's studies have focused on structural elucidation of novel molecules and pathways that serve as pro-resolving and/or endogenous anti-inflammatory chemical signals.

Dr Serhan and personnel

To meet this overall mission, Dr. Serhan is currently the program director of a federally supported NIH Program Project grant, Resolution Mechanisms in Acute Inflammation: Resolution Pharmacology. He is also Principal Investigator on the NIH research grant entitled Blood Cell Lipoxygenase Products: Formation and Action, funded since 1987 and receiving a MERIT Award. He also serves as mentor for post-doctoral fellowships including the Arthritis Foundation Fellowship awarded to Dr. Kie Kasuga (2006–2008). Jan Schwab, M.D, Ph.D. was the recipient of a Deutsche Forschungsgemeinschaft Fellowship (2005–2006). Dr. Matthew Spite received an NIH NRSA Fellowship (2008–2011). Dr. Lucy Norling received the Arthritis Research Campaign Fellowship (U.K.; 2008–2010).

Until recently, the resolution of inflammation was widely believed to be a passive rather than active process. Uncontrolled inflammation is now appreciated as a unifying pathophysiologic basis for many widely occurring chronic diseases, including Alzheimer's disease, cardiovascular disease and asthma, as well as the more traditional diseases associated with aberrant inflammation such as arthritis and periodontal disease. Dr. Serhan's current research focuses on the cellular and molecular mechanism(s) that govern endogenous anti-inflammation and resolution mechanisms in inflammation. From his research program, a body of evidence has emerged indicating that the resolution of inflammation is an active process. Dr. Serhan's approach in elucidating the molecular map or resolution circuitry involves a multidisciplinary systems biology approach employing lipid mediator informatics, cellular and molecular analyses integrated in a systems approach to elucidate critical biochemical pathways in the resolution response in vivo. The evidence that resolution is an active process comes from Dr. Serhan's discovery of the endogenous anti-inflammatory and pro-resolving chemical mediators that possess potent anti-inflammatory and tissue protective properties as well as activate previously unappreciated anti-microbial defenses mechanisms in host mucosal epithelia.

Dr Serhan speaking at Royal Academy of Science

Dr. Serhan's results demonstrated the assembly and activation of anti-inflammatory, pro-resolving lipid mediator circuits activated during the resolution phase of acute inflammation. These include the discovery, structural elucidation, and temporal-spatial distinct actions of the lipoxins, resolvins, protectins, and most recently the maresins. Each of these families of mediators is biosynthesized within the resolution phase to promote the return of the host tissues to homeostasis. Widely used drugs, such as aspirin, have a unique and direct impact on these biosynthetic circuits of resolution, in that they jump-start resolution by triggering the biosynthesis of endogenous epimers of these lipid mediators, termed aspirin-triggered lipid mediators, specifically, aspirin-triggered lipoxins (15-epi-lipoxins), aspirin-triggered 17®-series resolvins, and protectins. The structural elucidation of these pathways and mediators, identification of their anti-inflammatory and pro-resolving receptors and establishing their pro-resolving actions are discoveries that formulate the basis of this current paradigm shift in our appreciation of resolution as an active process.

These CET&RI discoveries have already provided a new appreciation of endogenous anti-inflammatory mechanisms and the return of tissues to homeostasis following inflammatory challenge. Moreover, they give opportunities to treat many common human diseases, where unresolved inflammation is a component of disease pathophysiology, with small molecule agonists of resolution based on the natural biotemplates of the lipoxins, resolvins, protectins and maresins. Knowledge of these pro-resolving biochemical circuits and previously unknown novel families of lipid-derived mediators also links the importance of dietary essential omega-3 fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, in healthy diets and their deficiencies to dysregulated resolution as well as the potential to correct defective resolution mechanisms. The control of the inflammatory response in the perioperative stage and the pain associated with chronic inflammation and post-surgical events are of increasing importance in the practice of anesthesia and pain management. Dr. Serhan's research provides new avenues to control inflammation and its natural resolution pathways with precision. These ongoing studies now open the new field of resolution pharmacology and its potential uses in human disease.

Protocols

Contact

Address
  • Harvard Institutes of Medicine Bldg
  • 77 Avenue Louis Pasteur (HIM 829)
  • Boston, MA 02115
Phone & Fax
  • Phone: 617-525-5001
  • Fax: 617-525-5017