2016 Ross Prize in Molecular Medicine: Resolution of Inflammation

2016 Ross Prize in Molecular Medicine: Resolution of Inflammation

Monday, June 13, 2016

The New York Academy of Sciences

Presented By

 

The Ross Prize in Molecular Medicine was established in conjunction with the Feinstein Institute for Medical Research and Molecular Medicine. The Ross Prize recognizes biomedical scientists whose discoveries have changed the way medicine is practiced. The prize is awarded to midcareer scientists who have made a significant impact in the understanding of human disease pathogenesis and/or treatment and who hold significant promise for making even greater contributions to the general field of molecular medicine.

The 2016 Ross Prize in Molecular Medicine will be awarded to Dr. Charles N. Serhan for his important discoveries in identifying bioactive mediators and cellular pathways critical in the resolution of inflammatory diseases. With his instrumental finding that inflammation is an active process, Dr. Serhan has undertaken a multidisciplinary systems biology approach to elucidate the underlying molecular mechanisms of various inflammatory pathologies and develop novel compounds for treating these diseases.

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Agenda

* Presentation times are subject to change.


Monday, June 13, 2016

10:00 AM

Registration and Refreshments

10:30 AM

Welcome and Introductory Remarks
Kevin J. Tracey, MD, The Feinstein Institute for Medical Research
Jack and Robin Ross, The Feinstein Institute for Medical Research Board of Directors
Daniel Radiloff, PhD, The New York Academy of Sciences

Session I: 2016 Ross Prize in Molecular Medicine Presentation and Lecture

11:00 AM

2016 Ross Prize in Molecular Medicine Announcement and Presentation
Lars Klareskog, MD, PhD, Karolinska Institutet

11:10 AM

2016 Ross Prize in Molecular Medicine Acceptance
Charles N. Serhan, PhD, DSc, Brigham and Women's Hospital & Harvard Medical School

11:15 AM

Structural Elucidation of Novel Mediators in Resolution of Infectious Inflammation and Tissue Regeneration in Human Tissues
Charles N. Serhan, PhD, DSc, Brigham and Women's Hospital & Harvard Medical School

12:15 PM

Luncheon

Session II: Emerging Approaches for Targeting Inflammatory Diseases

1:15 PM

Resolution Pharmacology: Innovation in the Treatment of Chronic Diseases
Mauro Perretti, PhD, The William Harvey Research Institute, Queen Mary University of London

2:15 PM

Inflammation, Homeostasis, and Disease
Ruslan M. Medzhitov, PhD, Yale School of Medicine, Howard Hughes Medical Institute

3:15 PM

Closing Remarks
Kevin J. Tracey, MD, The Feinstein Institute for Medical Research

3:30 PM

Adjourn

Speakers

Lars Klareskog, MD, PhD

Karolinska Institutet

Ruslan M. Medzhitov, PhD

Yale School of Medicine, Howard Hughes Medical Institute

Ruslan Medzhitov obtained his PhD from Moscow State University in 1993. After postdoctoral training with Charles A. Janeway Jr., Medzhitov became an assistant professor in 1999 at Yale University School of Medicine in the section of Immunobiology. He is currently the David W. Wallace Professor of Immunobiology at Yale University School of Medicine and an investigator of the Howard Hughes Medical Institute. His research interests include biology of inflammation, innate immunity, mechanisms of allergic reactions, cell signaling and gene regulation. Medzhitov is a member of the National Academy of Sciences, National Academy of Medicine, and European Molecular Biology Organization, and he is a fellow of the American Academy of Microbiology.

Mauro Perretti, PhD

The William Harvey Research Institute, Queen Mary University of London

Since 1991 Mauro Perretti has been interested in studying the process of white blood cell trafficking with an initial focus on Annexin A1 (then called lipocortin). Determining the impact of endogenous Annexin A1 in human neutrophil biology (Nat Med 1996) forged the pioneering concept of 'endogenous anti-inflammatory mediators. Over the last decade his interests have branched out on the investigation of specific endogenous mediators and pathways (e.g. melanocortins, galectins, calcitonin and, more recently, resolvins and chemerin peptides)—mainly studied in the context of experimental and human arthritis, sepsis and reperfusion injury, all in all making an internationally recognised contribution to the resolution of inflammation research area. Presently, the focus of his research is on pro-resolving receptors attempting to understand their biology and define their pro-resolving signature to inform innovative therapeutic approaches to exploit the resolution concept—his long-term aim is to add Resolution Pharmacology to the textbooks of Pharmacology of next decade. To date, Mauro Perretti has published over 320 peer-reviewed articles, with an H Factor of 72 and more than 18,000 citations.

Trained in Medicinal Chemistry in Florence (1985) followed by a Master in Pharmacology and Toxicology (1988), Mauro gained his PhD in London (1996) with a personal chair awarded in 2001. Mauro has long been involved in managing and strategic leadership for the William Harvey Research Institute (from 2006) and more recently the School of Medicine (2015) with his role as Dean for Research.

Charles N. Serhan, PhD, DSc

Brigham and Women's Hospital & Harvard Medical School

Charles is the Simon Gelman Professor of Anaesthesia (Biochemistry and Molecular Pharmacology) at Harvard Medical School, Professor of Oral Medicine, Infection and Immunity at HSDM, and since 1995 Director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Women's Hospital. Charles received a BS in biochemistry from Stony Brook University followed by a doctorate in experimental pathology and medical sciences from New York University School of Medicine. He was a visiting scientist and post-doctoral fellow at the Karolinska Institutet, Stockholm with Professor Bengt Samuelsson, 1982 Nobel Laureate. In 1987, he joined the faculty at Harvard Medical School and received an honorary degree from Harvard University (1996).

He has received several awards including an NIH MERIT award (2000) and has delivered more than 50 keynote and plenary lectures. Among these, the 2008 William Harvey Outstanding Scientist Medal and elected AAAS Fellow in 2011. In 2010, he received the Society for Leukocyte Biology–Bonazinga Award, American College of Rheumatology Hench Award Lecture in 2011, Mérieux 2013 Laureate and the 2013 Oh-Dang International Prize from Korea.

Professor Serhan is author of 523 publications, 4 books, and over 463 US patents.

Kevin J. Tracey, MD

President and CEO, The Feinstein Institute for Medical Research

Abstracts

Resolution Pharmacology: Innovation in the Treatment of Chronic Diseases
Mauro Perretti, PhD, William Harvey Research Institute at Queen Mary University of London

It is now appreciated that a coordinated inflammatory reaction requires a pro-inflammatory phase followed by a resolution phase with the consequence that an effective resolution program prevents progression from acute inflammation to persistent chronic inflammation. How can we harness this knowledge to improve the clinical management of inflammatory diseases? We propose that innovation exploiting the science of resolution of inflammation would lead to the development of novel anti-inflammatory drugs with the establishment of Resolution Pharmacology: such therapeutics could complement, if not represent, an alternative to current therapies (all developed by assessing their ability to block specific pro-inflammatory mediators) and—we predict—be burdened by a much lower degree of side effects. It is plausible that pro-resolving based therapeutics might be suitable for subsets of patients, perhaps where expression of specific receptors is augmented or specific mediators are deficient. We propose that definition of cell-specific pro-resolving signaling and downstream phenotypic responses would and should guide the development of novel molecules that act as agonists at pro-resolving receptor or therapeutic approaches that elevate the expression of endogenous pro-resolving mediators.
 
Resolution Pharmacology will enable the development of innovative therapeutics leading to an improved way on how we manage the complex, multi-morbidity, markedly debilitating and highly impacting diseases.

Structural Elucidation of Novel Mediators in Resolution of Infectious Inflammation and Tissue Regeneration in Human Tissues
Charles N. Serhan, PhD, DSc, Harvard Institutes of Medicine, BWH and Harvard Medical School

Uncontrolled inflammation is a component of many widely occurring chronic diseases. Using a systems approach with self-limited inflammatory infectious exudates to map tissue events, cell traffic and identification of protein and chemical mediators, we identified 3 structurally distinct families of potent essential fatty acid-derived (EPA, DPA, DHA) novel mediators, termed resolvins, protectins and maresins. Each family member is chemically unique and functions as a pro-resolving mediator that controls the duration and magnitude of acute inflammatory responses in pico- to nanogram range. The biosynthetic pathways and potent mediators from resolvin, protectin and maresin bioactive-metabolomes are coined specialized pro-resolving mediators (SPM). Mapping of these resolution circuits provides new avenues to probe the molecular basis of many diseases (CN Serhan, Nature 2014). This presentation will give an overview of our recent advances on SPM biosynthesis and functions. We use LC-MS-MS mediator-metabololipidomics targeted to profile SPM in human tissues (serum, plasma, breast milk, adipose and brain), which uncovered new pathways that stimulate tissue regeneration and bacterial clearance. Several SPM are in clinical development and in ongoing human trials. Identification of SPM during inflammation-resolution indicates that resolution is an active programmed process challenging the old concept that resolution is passive, where chemotactic molecules dilute and simply wane to resolve exudates. These findings indicate that resolution pathways may underlie prevalent diseases as failed resolution and open the potential for resolution physiology and resolution-based pharmacology. The author acknowledges support of NIH grants P01GM095467, R01GM38765, P01HL108801 and R01DE025020.

Inflammation, Homeostasis and Disease
Ruslan Medzhitov, PhD, Howard Hughes Medical Institute (HHMI), Yale University School of Medicine

Inflammation is an adaptive response to infection, tissue injury and other alterations of normal tissue function and homeostasis. The inflammatory response consists of four universal components: inflammatory triggers, sensors, mediators and target tissues. The inflammatory trigger can be an infectious agent, damaged or malfunctioning tissue. Inflammatory sensors are receptors and cell types that express them, including TLRs expressed on macrophages and other tissue resident cells. Inflammatory mediators comprise a large class of molecules that includes inflammatory cytokines, chemokines, bioactive amines and eicosanoids. Finally, the targets of the inflammatory response are the tissues responsive to a particular set of inflammatory mediators under a given condition. Depending on the nature of the inflammatory trigger, different combinations and quantities of the inflammatory mediators are produced by sensor cells. The inflammatory pathway is regulated at the level of all four components of the pathway. The principles of inflammatory regulation and their implications for normal physiology and pathology will be the focus of this presentation.

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