Departmental Research Programs

Overview

The Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women's Hospital is involved in laboratory and clinical research at the forefront of academic medicine. The mission of this research is to understand the mechanisms of disease that underlay the causes and conditions during and after surgical anesthesia and other operative procedures, and to apply this understanding to develop new and better treatments and thus to advance the clinical practice of anesthesia.

Research in the department is funded primarily through grants from the National Institutes of Health, and is conducted by both basic scientists and by clinical anesthesiologists. The organization of the basic research laboratories reflects the focussed interest of the department in the problematic areas of surgical anesthesia and its immediate sequelae, in chronic and acute pain and in other medical problems not directly related to anesthesia, such as myocardial muscle degeneration, periodontal disease and nerve regeneration, muscular dystrophy and spinal cord injury. In this regard, the departmental investigators often collaborate with researchers in other departments at BWH, at the medical school and other Harvard University teaching hospitals, and with many nationally and internationally known researchers at other institutions. In several research projects, successful efforts have supported collaborations between industry and departmental investigators, both at the lab bench and in the operating room. These activities have not only brought additional resources to the department and the hospital but have also facilitated a strong translational pathway for the development of new drugs and procedures.

Education

Education is a major responsibility in the department's research activities, enabling residents, post-graduate fellows, medical students, graduate students and undergraduates to participate in modern medical research. For more than 30 years the department has participated in the NIH- sponsored Harvard Anesthesia Training Grant that funds two year post-residency Anesthesia Fellows. There is also an active summer student program for undergraduates, and graduate students from Harvard and MIT have conducted their dissertation research in the Anesthesia Research Laboratories.

In the past fifteen years the department's research activities have increased more than four-fold, and continued to grow during the five year period covered by this report. The following passages describe in more detail the resources and organization of departmental research, and the activities and accomplishments of individual Principal Investigators.

Resources and Productivity

In 2008 research in the Anesthesiology Department was supported by 32 NIH grants and sub-contracts, of which 21 were individual investigator (R-01) grants, 4 were Program Project Grants and 1 was a P50 Center Grant and 6 sub contracts. In addition, there were 27 Sponsored Research Projects (private industry), many of the latter being clinical trials.

Three Fellowships had been awarded to researchers in training.

The five laboratory Research Centers, comprised of the Center for Experimental Therapeutics and Reperfusion Injury, Cardiovascular Research Laboratories, Center for Molecular Anesthesia, the Tissue Engineering Center and the Center for Pain Research, are housed in locations within the hospital totaling 27,132 square feet. In addition, there are many interdisciplinary projects that are conducted with investigators in other departments in Brigham and Women's Hospital, other institutions affiliated with Harvard Medical School, the larger University, and throughout the world. These collaborations, in turn, bring a rich stream of visiting scientists to our department, providing opportunities for students and residents to learn a broad and diverse range of subjects.

In 2008 there were 22 faculty conducting independent laboratory research and 22 faculty conducting clinical research.

Faculty serve on a broad range of scientific committees, including the editorial boards of the leading journals in anesthesia, inflammation and pain, research committees of the American Society of Anesthesiologists and the International Association for the Study of Pain, and four different Scientific Review Groups of NIH's Center for Scientific Review.

The department sponsors four annual named lectures on scientific and clinical topics that have been delivered by internationally prominent figures, and also annually sponsors the Gelman Scientific Symposium on Inflammation.

Gary Strichartz, PhD
Vice-Chairman for Research

The Pain Research Center

The Pain Research Center focuses on interdisciplinary programs investigating cellular and ionic mechanisms of acute, chronic (e.g., neuropathic) and cancer-related pain, as well as the pharmacology of intravenous, local, and general anesthetics, and the pharmacology of opioid tolerance. Other areas of investigation include alternative therapies for relief of acute and chronic pain, design of long-acting local anesthetics for reversible blockade of neurologic functions, molecular biology of ion channels and pre-emptive analgesia. This Center is directed by Professor Gary Strichartz, PhD, a leader in research on local anesthetics and pain mechanisms.

The Center for Experimental Therapeutics and Reperfusion Injury

The Center for Experimental Therapeutics and Reperfusion Injury focuses on the molecular biology of inflammation, as well as acute and chronic ischemia and reperfusion injury, with a particular focus on the role of lipid-derived mediators in regulating leukocyte function. In recent years, groups within the center have discovered distinct classes of these lipid mediators, lipoxins, that inhibit and regulate responses in neutrophils involved in inflammation and reperfusion injury. This group is led by Charles N. Serhan, PhD, a world authority on bioactive lipids, eicosanoids and lipoxins.

The Center for Molecular Anesthesia

The Center for Molecular Anesthesia focuses on the molecular biology of Ca2+ metabolism in striated muscle, and specifically on mechanisms governing Excitation-Contraction Coupling. One special area of interest is Malignant Hyperthermia, a pharmacogenetic disease that is caused by exposure to volatile anesthetics. Other areas of investigation include gene therapy of Duchenne’s Muscular Dystrophy using skeletal muscle stem cells as the gene delivery vehicle and expression profiling of human heart failure. This group is led by a clinician-scientist, P. D. Allen, PhD, MD, who is a world authority on the molecular biology of E-C coupling.

Center for Tissue Engineering

Our Center for Tissue Engineering is led by the Chairman, Charles Vacanti, MD. The goal of the research  is to generate new functional tissue utilizing autologous cells associated with synthetic, biodegradable, biocompatible polymer scaffolds. The scaffolds provide anchorage sites to prevent dispersion of cells from the site of implantation, as well as structural cues and a template to guide the generation of new tissue. The use of a novel adult-derived stem cell in combination with such scaffoldings is also being explored. Specific tissue to be studied will include cartilage, bone, nerves, tendon, ligament, skin and islets. Preliminary experiments have resulted in the generation of functional spinal cord tissue in SCI rats as well as the generation of islets using adult derived stem cells isolated from the pancreas in other animals.

Center for Regenerative Medicine

Piero Anversa, MD, directs the Center for Regernative Medicine, a joint research program with the Department of Medicine.  Their research challenges the accepted but never proven paradigm that the adult heart is a post-mitotic organ composed of an irreplaceable number of parenchymal cells, established at birth.  The work is based on the premise that the heart is a self-renewing organ in which a stem cell compartment controls the physiologic turnover of cardiac cells and conditions myocardial aging and tissue regeneration in pathologic states.  The long-term goal is the understanding of the origin and developmental control of cardiac progenitor cells, their distribution in the heart and mechanisms of aging, the etiology of their death and senescence, and their therapeutic potential for the aged and infarcted heart.

Laboratory of Nanomedicine and Biomaterials

The Laboratory of Nanomedicine and Biomaterials is a multi-disciplinary group of chemists, chemical engineers, cell and molecular biologists, and physicians who are focused on the applications of micro- and nanotechnologies to development and engineering of smart nanoparticles for therapeutic and diagnostic applications. Other areas of focus in the group include drug target identification and validation and high throughput synthesis and screening of nanomaterials for drug delivery. The group is led by Omid Farokhzad, an anesthesiologist-scientist with expertise in interventional pain medicine, who has pioneered the combinatorial development and screening of multifunctional nanoparticles for a myriad of clinical applications.

Laboratory for Aging Neuroscience

The Laboratory for Aging Neuroscience, led by Gregory Crosby, MD and Deborah Culley, MD, is interested in the aging brain and the impact general anesthesia and perioperative events have on it. Cognitive impairment lasting days to months after surgery and general anesthesia is a very common and distressing source of postoperative morbidity in the elderly. The laboratory is testing the hypothesis that general anesthesia, which is controlled coma, contributes to this problem.  Our hope is that better understanding of the impact of perioperative events on the neurobiology of the aged brain will ultimately translate into improved cognitive outcome after surgery and anesthesia in elders.

CABG Genomics Program

The Perioperative Genomics Research Group within the Department examines the impact of genetic variation upon outcomes after cardiac surgery.  The CABG Genomics Program is a multi-institutional study of genomic influences on adverse cardiac and non-cardiac outcomes after coronary artery bypass graft (CABG) surgery.  The program is led by a team including Drs. Simon Body, Stanton Shernan, Amanda Fox, Jochen Muehlschlegel, Tjorvi Perry, and Kuang-Yu Liu in this department, together with Dr. Charles Collard of the Texas Heart Institute.  To date, the group has enrolled over 1750 primary CABG surgical patients in four surgical centers, performing genomic analyses and perioperative biomarker assessment and recording detailed in-hospital and post-discharge followup using a case report form and study database developed by Departmental IT staff.  This research has uncovered several markers predictive of an increased risk of adverse outcomes after cardiac surgery.  These research efforts are important to improving cardiac surgical risk stratification as well as to future development of pharmacologic and medical interventions that will improve perioperative morbidity and mortality.

Clinical Research

The clinical research program is equally active and diverse with particular strengths in obstetric, regional and ambulatory anesthesia, neurophysiological monitoring, and post-operative pain management. There are currently over 60 clinical research projects underway led by members of the department. Some clinical research projects result from the continuation of laboratory studies in the clinical arena.

Translational Pain Research

The Translational Pain Research Group works to bring laboratory research into a safe and effective clinical research setting.  The group provides a wealth of educational information on chronic pain, and offers the opportunity for patients to participate in clinical trials of novel approaches to chronic pain therapies.