
Pharmacologic Resolution of Inflammation as a Novel Therapeutic Approach
Tuesday, October 28, 2014
Uncontrolled, chronic inflammation is now considered a major component of many widespread diseases, which are now well-recognized as 'inflammatory diseases.' These include arthritis, asthma, atherosclerosis and peripheral vascular disease, Alzheimer’s disease, periodontal disease and cancer. There is general agreement that inflammation is not likely to be the causative factor in these diseases, but that it plays a key role in disease progression, tissue dysfunction and ultimately organ failure. In recent years, evidence has emerged that resolution of inflammation is a biochemically active process driven by multiple chemical mediators. Elucidation of the biochemical pathways contributing to the resolution of inflammation has provided many new anti-inflammatory targets and an opportunity for resolution-based pharmacology for treatment and prevention of inflammatory diseases. This symposium reviews recent discoveries and advances in the field, and demonstrates how this work translates into new approaches and new pharmacology to treat old diseases.
*Networking reception to follow.
This event will also be broadcast as a webinar.
Please note: Transmission of presentations via the webinar is subject to individual consent by the speakers. Therefore, we cannot guarantee that every speaker's presentation will be broadcast in full via the webinar. To access all speakers' presentations in full, we invite you to attend the live event in New York City when possible.
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Agenda
* Presentation titles and times are subject to change.
October 28, 2014 | |
8:30 AM | Registration and Continental Breakfast |
9:00 AM | Welcome and Introductory Remarks |
9:15 AM | Pro-Resolving Lipid Mediators in Clearing Inflammation & Infection |
9:45 AM | Keynote Presentation |
10:20 AM | Resolving Vascular Injury: Resolvins and Maresins Influence Vascular Remodeling |
10:50 AM | Networking Coffee Break |
11:20 AM | New Mechanisms and Therapeutic Potential of Pro-resolving Mediators in Advanced Atherosclerosis |
11:50 AM | Genetics of Inflammation in the Brain and Alzheimer’s Disease Risk |
12:20 PM | Networking Lunch Break and Poster Session |
1:30 PM | Omega-3 Fatty Acids with Antioxidants Increase Amyloid-β Phagocytosis and Attenuate Inflammation in Alzheimer Disease Patients: Role of Resolvin D1 |
2:00 PM | Resolvins in Airway Inflammation: An Effective Therapy for Chronic Obstructive Pulmonary Disease? |
2:30 PM | Networking Coffee Break |
3:00 PM | Specialized Pro-Resolving Mediators in Allergic Airway Responses, Asthma and Acute Lung Injury |
3:30 PM | Suppression of Cell Debris-stimulated Tumor Growth by Resolvin Mediated Clearance |
Late-Breaking Early Career Investigator Presentations | |
4:00 PM * | Accelerating Inflammation Resolution to Counteract Chemical Cutaneous and Pulmonary Injury * The 4:00 pm talk will not be broadcast as part of the live webinar |
4:15 PM | Specialized Proresolving Mediators Differentially Affect Platelet Function |
4:30 PM | ETC-1002 Modulates Macrophage Immune Response, Attenuates Vascular Inflammation and Prevents Progression of Experimental Atheroma in LDL Receptor-Deficient Mice |
4:45 PM | Spontaneous Pro-Resolution Mediators (SPM’s) in Paediatric Cystic Fibrosis (CF) Lung Disease |
5:00 PM | Closing Remarks |
5:05 PM | Networking Reception |
6:00 PM | Adjourn |
Speakers
Organizers
Charles N. Serhan, PhD, DSc (hc)
Brigham & Women's Hospital, Harvard Medical School
Charles Nicholas Serhan is the Simon Gelman Professor of Anaesthesia (Biochemistry and Molecular Pharmacology) at Harvard Medical School and Professor of Oral Medicine, Infection and Immunity at HSDM Harvard University. Since 1995, he is Director of the Center for Experimental Therapeutics and Reperfusion Injury at BWH. Professor Serhan received Bachelor of Science in biochemistry from Stony Brook University and received his doctorate in experimental pathology and medical sciences New York University (NYU) School of Medicine. He was a visiting scientist at the Karolinska Institutet, Stockholm, Sweden and post-doctoral fellow. In 1996, he received an honorary degree from Harvard University. Dr. Serhan was awarded an NIH MERIT Award and the Outstanding Scientist Award in Inflammation Research. He delivered the 2005 NIH Kreshover Lecture and LSU Chancellor’s Award in Neuroscience in 2006. Received the 2008 William Harvey Outstanding Scientist Medal. In 2010, delivered the Kern Lecture and received Soc. Leukocyte Biology 2010-Bonazinga Award. Dr. Serhan was elected Fellow of AAAS in 2011, delivered the Tabak NIH-Lectureship, 2011 ACR Hench Lecture and the Honorary Fellow from Queen Mary University. NIH/NCI Distinguished Lecturer STARS in Nutrition and Cancer (2012), 2013 JLR Lectureship Award, 2013 UC Dublin Honorary DSc and 2014 Sterling Drug Award.
George B. Zavoico, PhD
MLV & Co.
George B. Zavoico, PhD, is Director, Life Sciences Research and Senior Equity Research Analyst at MLV & Co, a boutique investment bank and institutional broker-dealer based in New York. He has 10 years of experience as a life sciences equity analyst writing research on publicly traded equities and, beginning in 2009, helped to establish and expand the Healthcare research team at MLV. From 2005 to 2009, Dr. Zavoico was an Equity Analyst at Westport Capital Markets and Cantor Fitzgerald. Prior to 2005, Dr. Zavoico established his own consulting company serving the biotech and pharmaceutical industries by providing competitive intelligence and marketing research, due diligence services, and guidance in regulatory affairs. He also wrote extensively on healthcare and the biotech and pharmaceutical industries for periodicals targeting the general public and industry executives. Dr. Zavoico began his career as a Senior Research Scientist at Bristol-Myers Squibb Co., moving on to management positions at Alexion Pharmaceuticals, Inc. and T Cell Sciences, Inc. (now Celldex Therapeutics, Inc.). He has a BS in Biology from St. Lawrence University and a PhD in Physiology from the University of Virginia. He held post-doctoral fellowships at the University of Connecticut School of Medicine and at Harvard Medical School/Brigham & Women’s Hospital. He has published over 30 papers in peer-reviewed journals and has co-authored four book chapters.
Jennifer S. Henry, PhD
The New York Academy of Sciences
Speakers
Satya Achanta, DVM, PhD
Duke University School of Medicine
Dr. Satya Achanta is a research associate at the Duke University School of Medicine. Dr. Achanta received his veterinary degree from India and worked as a mixed animal practitioner for two years before he moved to the United States. Dr. Achanta obtained his PhD in Veterinary Biomedical Sciences at the Center for Veterinary Health Sciences, Oklahoma State University. Then, he joined as a postdoctoral research associate in Dr. Sven Jordt’s laboratory at Yale University where he tested the therapeutic potential of pro-resolving agents in different injury models. As a North Carolina state-licensed veterinarian, with experience in large animal medicine, Dr. Achanta is interested in developing cutaneous and pulmonary injury models in large mammals and screen potential therapeutic agents based on mechanistic studies.
Michael S. Conte, MD
University of California-San Francisco
Dr. Michael Conte received his medical degree in 1986 at Albert Einstein College of Medicine. He completed his surgical residency at New York Hospital-Cornell Medical Center in 1993, which included a two year research fellowship at Brigham and Women's Hospital (BWH) and Massachusetts Institute of Technology in Boston. He completed his vascular surgery training in 1994 as the John Homans Fellow at BWH and Harvard Medical School (HMS), in Boston. Dr. Conte was an Assistant Professor of Surgery at Yale University from 1994-1997, and a member of the Boyer Center for Molecular Medicine. Subsequently he returned to BWH where he served as Assistant Professor (1997-2001) and then Associate Professor (2001-2008) of Surgery at HMS. From 2002-2008, he was the Director of Vascular Surgical Research at BWH and from 2005-2008, he was Co-Director of the Clinical Trials Group at the Center for Surgery and Public Health (a joint initiative between HMS, BWH, and the Harvard School for Public Health). Dr. Conte is a member of many professional organizations, including the Society for Vascular Surgery and the Society of University Surgeons. Dr. Conte has also been an invited lecturer for many regional, national, and international meetings and conferences. In 2006, he received the Distinguished Achievement Award from the New York Weill Cornell Medical Center Alumni Council. He is on the Editorial Board for Vascular and Endovascular Surgery, Vascular Medicine, Journal of Vascular Surgery, and Vascular. He has served as an Associate Editor for Circulation.
Milan Fiala, MD
David Geffen School of Medicine at UCLA
Milan Fiala, MD is a Research Professor in the UCLA Department of Surgery. After Internship, Dr. Fiala trained in Oncology at Massachusetts General Hospital and in Epidemiology at Harvard School of Public Health. He has had a long a research career at UCLA in Virology and Immunology of neurological diseases. His recent interests are immunological therapies of inflammation in neurological diseases, including Amyotrophic lateral sclerosis and Alzheimer disease. His recent discoveries open new approach to treating inflammation in ALS through IL-6 inhibition and preventing Alzheimer disease by nutritional supplementation with omega-3 fatty acids, antioxidants, vitamin D3 and resveratrol.
Sergey Filippov, MD, PhD
Esperion Therapeutics Inc.
Sergey Filippov, MD, PhD, has an extensive experience in the cardiovascular sciences and pharmaceutical industries. After completing his postdoctoral training in 2000, Sergey has been appointed as a Research Investigator at Molecular Medicine and Genetics, University of Michigan Medical School. In 2005, Sergey transitioned to the pharmaceutical industry by joining the Vascular Biology Department at the Esperion Division of Pfizer where he focused his research on mechanisms of oxidative modifications of lipoproteins and vascular inflammation. In 2007 Sergey transferred to the division of Cardiovascular and Metabolic Diseases, Pfizer Global R&D where he served as a Biology Lead on the team developing new therapeutic interventions for the treatment of cardiovascular diseases. In December 2010, Sergey joined Esperion Therapeutics as a Principal Scientist leading macrophage biology efforts focusing on further understanding of MOA for the lead compound. Sergey’s research interests include cell and matrix biology of chronic inflammation associated with atherosclerosis and vascular complications of type 2 diabetes. Sergey earned an MD from Ivanovo State Medical Academy and a PhD in Cell Biology from Yaroslavl State Medical Academy, Russia.
Gabrielle Fredman, PhD
Columbia University
Gabrielle Fredman received a PhD from Boston University in 2009. She then joined the laboratory of Dr. Charles Serhan at Brigham and Women’s Hospital/Harvard Medical School to study lipid mediators in the resolution of inflammation. After a brief post doc in the Serhan laboratory, Gabrielle joined the laboratory of Dr. Ira Tabas at Columbia University to apply her research interests, which are the actions of lipid mediators in advanced atherosclerosis.
Katie L Lannan, MS
University of Rochester
Katie Lannan is a graduate student in the Department of Microbiology and Immunology at the University of Rochester in the laboratory of Dr. Richard Phipps. Her research focuses on modulation of platelet function, with specific emphasis on the use of novel agents to improve platelet storage and mitigate platelet activation. Katie has published in the area of red blood cell and platelet transfusion, and continues to investigate the platelet storage lesion. Her most recent work focuses on the ability of specialized pro-resolving lipid mediators to mitigate platelet function. Katie has had multiple opportunities to expand her training in translational science, including attending a NIH Clinical and Translational Science course and serving as a Howard Hughes Medical Institute fellow.
Bruce Levy, MD
Brigham & Women's Hospital, Harvard Medical School
Dr. Levy is the Chief of the Pulmonary and Critical Care Medicine Division of the Department of Internal Medicine at Brigham and Women’s Hospital. He has a long-standing interest in internal medicine and training the next generation of academic physicians and spent 13 years as the Director of the Medical Residency Program for Academics and Career Development. After graduating from the University of Pennsylvania School of Medicine in 1988, he performed his internship and residency at BWH. After training in the Harvard joint fellowship program in pulmonary and critical care medicine, he returned to BWH to be a chief medical resident in 1993. Since then, Dr. Levy has been a member of the Pulmonary and Critical Care Medicine Division at BWH where he sees patients in the Center for Chest Diseases and performs basic research. He is appointed as an Associate Professor of Medicine at Harvard Medical School and serves as a teacher of medical students, residents and fellows. Dr. Levy also volunteers in the community as the medical director of the New England Shelter for Homeless Veterans. He has been the recipient of several education and community service awards from BWH and HMS.
Dipak Panigrahy, MD
Beth Israel Deaconess Medical Center, Harvard Medical School
Dr. Panigrahy was accepted into medical school at Boston University at age 17. He trained in surgery with Dr. Roger Jenkins, who performed the first liver transplant in New England. Over the past decade, Dr. Panigrahy led angiogenesis and cancer animal modeling in the Judah Folkman laboratory. Dr. Panigrahy joined the Beth Israel Deaconess Medical Center in 2013, and in 2014 was appointed Assistant Professor of Pathology and currently has a laboratory in the Center for Vascular Biology Research.
Mauro Perretti, PhD
Queen Mary University of London
Since 1991 Dr. 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’ (recapitulated in a groundbreaking 1997 review) that has contributed to the current appreciation of the impact of the resolution of inflammation, or its lack of, in the context of human inflammatory pathology. 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 Dr. Perretti group is on pro-resolving receptors (e.g. ALX/FPR2; MC1R and MC3R, ChemR23) attempting to understand their physio-pathology and define their pro-resolving signature, using mouse and human cells, models of acute inflammation and proof-of-concept experiments in models of disease, with the ultimate aim to inform innovative therapeutic approaches to exploit the resolution concept. Dr. Perretti long-term aim is to add Resolution Pharmacology to the textbooks of Pharmacology of next decade.
Fiona Ringholz, MBBChir, MRCPCH
National Children’s Research Centre
Fiona Ringholz graduated medicine from the University of Cambridge in 2005 and is engaged in Higher Specialist training in Paediatrics with the Royal College of Physicians in Ireland. She is involved in a translational research project based between Our Lady’s Children’s Hospital, Crumlin, Dublin (the national referral centre for Paediatric Cystic Fibrosis (CF)) and Valerie Urbach’s lab at the National Children’s Research Centre in Dublin, Ireland. The aim of the project is to investigate the role played by Pro-Resolution Mediators in the pathogenesis of CF lung disease, and their potential application as candidate therapeutics for CF. Fiona Ringholz is registered as a Doctoral candidate at the Royal College of Surgeons in Ireland.
Charles N. Serhan, PhD, DSc (hc)
Brigham & Women's Hospital, Harvard Medical School
Charles Nicholas Serhan is the Simon Gelman Professor of Anaesthesia (Biochemistry and Molecular Pharmacology) at Harvard Medical School and Professor of Oral Medicine, Infection and Immunity at HSDM Harvard University. Since 1995, he is Director of the Center for Experimental Therapeutics and Reperfusion Injury at BWH. Professor Serhan received Bachelor of Science in biochemistry from Stony Brook University and received his doctorate in experimental pathology and medical sciences New York University (NYU) School of Medicine. He was a visiting scientist at the Karolinska Institutet, Stockholm, Sweden and post-doctoral fellow. In 1996, he received an honorary degree from Harvard University. Dr. Serhan was awarded an NIH MERIT Award and the Outstanding Scientist Award in Inflammation Research. He delivered the 2005 NIH Kreshover Lecture and LSU Chancellor’s Award in Neuroscience in 2006. Received the 2008 William Harvey Outstanding Scientist Medal. In 2010, delivered the Kern Lecture and received Soc. Leukocyte Biology 2010-Bonazinga Award. Dr. Serhan was elected Fellow of AAAS in 2011, delivered the Tabak NIH-Lectureship, 2011 ACR Hench Lecture and the Honorary Fellow from Queen Mary University. NIH/NCI Distinguished Lecturer STARS in Nutrition and Cancer (2012), 2013 JLR Lectureship Award, 2013 UC Dublin Honorary DSc and 2014 Sterling Drug Award.
Patricia J. Sime, MD
University of Rochester School of Medicine
Dr. Patricia J. Sime, MD, FRCP is currently Professor of Medicine, Chief of Pulmonary and Critical Care, and the Associate Chair for Research in Medicine. She received her medical degree and training in Pulmonary Medicine from Edinburgh University, Scotland. Following this she spent four years at McMaster University, Canada, where she received basic and translational scientific training in lung inflammation, gene transfer, chronic obstructive lung disease and fibrosis. Dr. Sime joined the University of Rochester in 1999. She is board certified in internal medicine and pulmonary medicine, and has practiced in the UK, Canada and the United States. Dr. Sime is a physician-scientist who focuses on the identification of novel targets for therapy in lung diseases, particularly diseases associated with inflammation and its resolution, and those characterized by fibrosis. Her recent work has focused on fibroblast biology, mediators, matrix regulation and abnormal metabolism in lung fibrosis and the regulation and therapeutic interventions for chronic obstructive pulmonary disease. Dr. Sime is a member of American Society for Clinical Investigation and a Fellow of the Royal College of Physicians (UK).
Rudolph E. Tanzi, PhD
Massachusetts General Hospital
Dr. Rudolph Tanzi is the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University, and Vice-Chair of Neurology and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital. Dr. Tanzi has been investigating the genetics of neurological disease since the 1980’s when he worked on the first study that used human genetic markers to find a disease gene (Huntington's disease). Dr. Tanzi co-discovered all three familial early-onset Alzheimer's disease genes and several other neurological disease genes including that responsible for Wilson’s disease. As leader of the Alzheimer’s Genome Project, Dr. Tanzi has identified many other genes for the common late-onset form of AD, including CD33 and ADAM10. His research on the role of zinc and copper in AD has led recently to ongoing clinical trials at Prana Biotechnology. Dr. Tanzi serves on dozens of editorial and scientific advisory boards, and as Chair of the Cure Alzheimer’s Fund Research Consortium. He has received numerous awards, including the two highest awards for Alzheimer's disease research: The Metropolitan Life Award and The Potamkin Prize. Dr. Tanzi was included on the list of the "Harvard 100 Most Influential Alumni" by 02138 magazine, and was chosen by the Geoffrey Beene Foundation as a “Rock Star of Science”. He was also recently voted one of the “Most Influential Scientific Minds in the World” for 2014 and one of the “Top 20 Translational Scientists of 2013”. Dr. Tanzi has co-authored over 460 research articles, including three of the top ten most cited AD papers. He also co-authored the popular trade books “Decoding Darkness: The Search for the Genetic Causes of Alzheimer’s Disease” and the recent New York Times Bestseller, “Super Brain” (and PBS show). In musical pursuits, Dr. Tanzi plays keyboards professionally, most recently with the musical group, Aerosmith and with Joe Perry.
Sponsors
For sponsorship opportunities please contact Perri Wisotsky at pwisotsky@nyas.org or 212.298.8642.
Academy Friend
Maresins Pharma, Inc.
Grant Support
This program is supported in part by a grant from AstraZeneca
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Abstracts
Pro-Resolving Lipid Mediators in Clearing Inflammation & Infection
Charles N. Serhan, PhD, DSc (hc), Brigham & Women's Hospital, Harvard Medical School
G Protein-Coupled Receptors in Resolution of Inflammation: Annexin, Lipoxin A4 and Resolvin D1
Mauro Perretti, PhD, Queen Mary University of London
Resolving Vascular Injury: Resolvins and Maresins Influence Vascular Remodeling
Michael S. Conte, MD, University of California-San Francisco
In cultured vascular smooth muscle cells (VSMC), SPM inhibit cell migration in a wound assay and chemotaxis to PDGF. They attenuate TNF-stimulated NFkB activation, monocyte adhesion, gene expression, and generation of reactive oxygen species. In a rabbit model of arterial angioplasty, local delivery of RvD2 attenuated leukocyte recruitment and reduced neointima formation. In a mouse model of carotid ligation, systemic (IP) administration of RvD2 and MaR1 reduced leukocyte recruitment, altered macrophage phenotype (favoring M2 vs M1), and significantly attenuated neointimal hyperplasia. We have measured local levels of SPM and their precursors in arterial tissues and in patients with vascular disease, and demonstrate the expression of some of the known SPM receptors in vascular cells. Taken together our findings indicate that i) biochemical pathways of resolution are operative in vascular injury; ii) SPM have direct effects on vascular cells; and iii) increased availability of SPM may favorably alter the healing response to acute vascular injury.
New Mechanisms and Therapeutic Potential of Pro-resolving Mediators in Advanced Atherosclerosis
Gabrielle Fredman, PhD, Columbia University
Genetics of Inflammation in the Brain and Alzheimer’s Disease Risk
Rudolph E. Tanzi, PhD, Massachusetts General Hospital
Omega-3 Fatty Acids with Antioxidants Increase Amyloid-β Phagocytosis and Attenuate Inflammation in Alzheimer Disease Patients: Role of Resolvin D1
Milan Fiala, MD, David Geffen School of Medicine at UCLA
Resolvins in Airway Inflammation: An Effective Therapy for Chronic Obstructive Pulmonary Disease?
Patricia J. Sime, MD, University of Rochester School of Medicine
Hypothesis: Pro-resolving lipid mediators (PRMs) have profound anti-inflammatory and pro-resolving effects on acute and chronic lung injury. Treatment with PRMs promote resolution: a novel and important therapeutic goal for inflammatory diseases caused by cigarette smoking.
Results: Using pre-clinical mouse models of acute and chronic cigarette smoke-incited inflammation, we have demonstrated that PRMs such as resolvin D1 (RvD1) dampen acute neutrophilic inflammation and promote its resolution through M2 pro-resolving macrophages. PRMs also prevent smoke-induced chronic inflammation and emphysema with reductions in apoptosis and oxidative stress. Studies in primary human lung cells revealed that RvD1 inhibits pro-inflammatory signaling by blocking both the MAPK and NF-kB inhibitors through a common regulatory kinase.
Conclusions: These studies show for the first time that pro-resolving mediators can be used to prevent inflammation and accelerate resolution/repair of lung injury due to both acute and chronic cigarette smoke exposure. Our results will pave the way for translational development of these exciting new compounds that have the potential to be effective therapies against human diseases of chronic inflammation and smoking. Supported by: NIH T32 HL066988, NIH R01HL110759-01, NIH P30ES01247, NIEHS T32ES007026, PhRMA Foundation, ULITR000042, GM038765
Specialized Pro-resolving Mediators in Allergic Airway Responses, Asthma and Acute Lung Injury
Bruce Levy, MD, Brigham & Women's Hospital, Harvard Medical School
Suppression of Cell Debris-stimulated Tumor Growth by Resolvin Mediated Clearance
Dipak Panigrahy, MD, Beth Israel Deaconess Medical Center, Harvard Medical School
Accelerating Inflammation Resolution to Counteract Chemical Cutaneous and Pulmonary Injury
Satya Achanta, DVM, PhD, Duke University School of Medicine
Specialized Proresolving Mediators Differentially Affect Platelet Function
Katie L Lannan, MS, University of Rochester
ETC-1002 Modulates Macrophage Immune Response, Attenuates Vascular Inflammation and Prevents Progression of Experimental Atheroma in LDL Receptor-Deficient Mice
Sergey Filippov, MD, PhD, Esperion Therapeutics Inc.
Spontaneous Pro-Resolution Mediators (SPM’s) in Paediatric Cystic Fibrosis (CF) Lung Disease
Fiona Ringholz, MB BChir, National Children’s Research Centre
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