CENTER FOR EXPERIMENTAL THERAPEUTICS & REPERFUSION INJURY
Opportunities in Multi-Disciplinary and Human Translational Cellular and Molecular Research: This basic research Center for Experimental Therapeutics and Reperfusion Injury was founded by Professor Simon Gelman and continues to offer many opportunities for discovery research and fellowship training in topics that are of interest in internal medicine, surgery, pathology and their respective specialties.
This research Center is devoted to multidisciplinary research efforts with a cluster of highly talented faculty members and affiliated faculty with unique scientific expertise focused on defining key molecular elements in the pathogenesis of reperfusion injury, a sequence of events that affects many diseases including asthma, cardiovascular diseases, pulmonary and renal disorders, as well as diseases with inflammatory components such as arthritis and periodontal disease. In addition to these clinical disease points, the underlying interactions between white blood cells and vascular & mucosal tissues evoke local acute inflammatory responses that can be initiated within the host by surgical stress and local inflammatory mediators and that persist in the perioperative arena and beyond.
The perioperative arena provides a wide, unmet clinical need for development of novel therapeutics to shorten perioperative holding times and eventual hospital stay. In many respects, the cell biology and molecular mechanisms that are involved in acute reperfusion injury as observed in the surgical arena resemble the cellular and molecular events that take place in acute inflammation and host defense. Hence, detailed understanding of these molecular mechanisms and cellular events can provide us with a wealth of new information that could have wide-ranging implications for the medical specialties and our appreciation of host defense, preventative medicine and novel therapeutics for diseases associated with inflammation and chronic pain.
Scope of Research in 2012 and beyond
The research programs within the Center take multidisciplinary team approaches to these unsolved puzzles in human diseases. The current tools of molecular medicine, namely biochemistry, cell and molecular biology, pharmacology, physiology and structural elucidation of small molecule natural products, all converge, with representatives from each discipline focused on elucidating key components in ischemia and reperfusion injury. This provides a unique opportunity for discovery and program development within a balanced training environment. This is evidenced by the substantial number of trainees and the strong extramural support for this Center over a dozen years. Importantly, a significant number of faculty and alumni fellows are PIs and faculty at prestigious institutions around the world.
Mission Statements & Goals of the CET&RI
An interdisciplinary research team of experienced as well as new investigators are assembled within the Center with the following general mission statements:
- To identify novel targets and pathways critical in regulating acute inflammation and its natural resolution and to establish the templates for physiologic small molecule resolution-based interventions.
- To elucidate the molecular mechanisms underlying reperfusion injury and identify novel therapeutic interventions that can prevent cell injury. a
From these two broad mission statements we created a platform for discovery with a focus on structural elucidation, molecular physiology, and pharmacology as they merge in systems biology, evaluating the cell biology of inflammation and reperfusion injury in animal models such as transgenic and knockout mice and genetically engineered larger animal models.
To accomplish our objectives, the Center brings together a group of investigators and faculty members with recognized expertise in biochemistry, pharmacology, physiology, physiological chemistry, cell biology, and molecular biology, all with a special interest in the function of white blood cells and their interactions with cells of the vessel wall, within inflammatory exudates as well as mucosal lining of the airway, eye and gastrointestinal tract. Hence, one focal strength of the Center is its multidisciplinary approach to the well-appreciated diseases associated with aberrant neutrophil activation and uncontrolled host-defense/infection that can occur during collateral tissue damage and local inflammation in a wide range of clinical scenarios as well as in ischemia-reperfusion injury or reflow tissue injury as in the operating room.
The individual research report narratives of the Center's faculty indicate the research focus in each principal investigator's laboratory and their recent discoveries that are funded by several extramural research sources. Current support includes grants obtained from the National Institutes of Health, American Heart Association, Arthritis Foundation, Fulbright Scholars Program and the Crohn's and Colitis Foundation, to name a few of the extramural supporting agencies of this center’s research mission. As a research cluster of very talented investigators in a strategic alliance to solve problems of fundamental importance in the biomedical sciences, the Center is placed in a highly unique position to rapidly translate basic research discoveries at the molecular and cellular level into potentially novel approaches and new treatments by shaping new thoughts regarding the pathobiology of human disease.
The opportunity for dialogue with clinicians and clinician-scientists provides scientists working in this Center the ability to articulate well informed hypotheses in their experiments, aimed to elucidate clinical observations and phenomena to provide insight and a basis for informed intervention. This alliance between clinicians, clinician-scientists and basic scientists within each laboratory within the Center places this group of investigators in a strong position to achieve success in their individual research programs.
The Longwood Medical Area
This Center’s laboratories and offices of our faculty members are located in the Harvard Institutes of Medicine, 8th Floor. This campus location provides an opportunity for daily interactions between individual laboratories and a framework for synergy with faculty members of the Center, their trainees, postdoctoral fellows and research associates as well as other investigators located within the Harvard Medical and greater Longwood
Labs & Principal Investigators
Professor Charles N. Serhan's laboratory focuses on structural elucidation of bioactive molecules. The overall mission is “To identify novel pathways and cellular targets critical in regulating neutrophil-mediated inflammation and to establish the templates for physiologic small molecule-based interventions.” In the CET&RI, the overarching mission is to define the molecular mechanisms underlying reperfusion injury and to identify novel therapeutic interventions that can prevent cell injury.
Charles N. Serhan, Ph.D. was appointed the first Endowed Distinguished Scientist at Brigham and Women’s Hospital and currently serves as Director of the Center for Experimental Therapeutics and Reperfusion Injury (CET&RI) at BWH. Dr. Serhan is a full Professor of Anaesthesia at Harvard Medical School and affiliated with the Department of Biological Chemistry and Molecular Pharmacology.
Professor Gregory L. Stahl's lab investigates the contribution of the innate immune system to tissue injury and inflammation following ischemia and reperfusion injury. During the past several years, Dr. Stahl's lab has focused on the contributions of the complement pathways responsible for the initiation of complement activation following ischemia/reperfusion, as well as the role of the early versus late complement components in mediating inflammation and tissue injury.
Gregory L. Stahl, Ph.D. is the Paul Allen Distinguished Professor at Brigham and Women's Hospital, Harvard Medical School. He obtained his PhD in Cardiovascular Physiology from Thomas Jefferson University in 1988. Dr. Stahl is a full Professor of Anaesthesia at Harvard Medical School.
The research activities in Hongwei Gao’s laboratory are focusing on revealing the molecular mechanisms that regulate inflammatory events during acute lung injury, sepsis, and inflammatory bone diseases. Specially, we are identifying the function of complements and their receptors in acute lung injury, sepsis, and inflammatory bone diseases.
Hongwei Gao, M.D. is an Assistant Professor of Anaesthesia at Harvard Medical School.