Brigham and Women’s Hospital

Center for Experimental Therapeutics & Reperfusion Injury

Research in the Center for Experimental Therapeutics & Reperfusion Injury focuses on structural elucidation of endogenous molecules that activate the resolution of acute inflammation, organ protection and tissue regeneration. Our overall mission is “To identify novel mediators, pathways, and cellular targets critical in promoting resolution of inflammation and reperfusion tissue injury and their relation to human disease.” Our studies currently focus on structural elucidation of novel molecules and pathways that are pro-resolving and anti-inflammatory chemical signals and elucidating the pro-resolving mechanisms in ischemia reperfusion injury to demonstrate resolution-based pharmacology.

We elucidated several new families of lipid-derived, local-acting chemical mediators, coined the Resolvins and Protectins, and most recently Maresins, that stimulate resolution of inflammatory responses in diverse animal disease models. We also designed novel therapeutic approaches using these structures as biotemplates, their biosynthetic pathways and receptors. New therapeutic approaches built with the knowledge of these signaling pathways could be more potent, selective and better tolerated since they are based on structures naturally evolved in these processes. Several of these new designer therapeutics that stimulate resolution of inflammation have already been shown to be effective in humans in early stage clinical trials.

Funding: P01HL108801 - Carbon monoxide: novel opportunities for therapy; P01HL108801 - Lipid mediator metabolomics; P01GM095467 - Resolution mechanisms in acute inflammation: resolution pharmacology; P01GM095467 -Core A and Core B:SPM-Lipidomics & metabolomics; P01GM095467 - Project 1 : novel specialized pro-resolving lipid mediators; R01GM038765-31 – Blood cell lipoxygenase products—formation and action
PI: Charles N. Serhan, Ph.D, D.Sc.
Email: cserhan@bwh.harvard.edu
Web page: http://research.bwhanesthesia.org/research-groups/cetri
Lab video: https://bwhclinicalandresearchnews.org/2017/01/04/searching-for-answers-in-inflammation/

Selected Publications:

Clinical Pain Research Center

The clinical pain research center is a part of the Pain Management Center at Brigham & Women's Hospital / Harvard Medical School. The centers main research focus involves the biopsychosocial influences on the experience of chronic pain. This includes individual differences in pain responses, and the neurobiological mechanisms by which psychosocial processes shape those individual differences. Some of the current projects focus on the impact of negative emotions and cognitions (e.g., pain-related catastrophizing) on neuroendocrine and inflammatory responses to pain, the potential benefits of non-pharmacologic therapies for chronic pain (e.g., meditation, cognitive-behavioral therapy, yoga), central nervous system pain-modulatory processes, and functional connectivity of pain circuitry in the brain.

Several of our studies use functional neuroimaging techniques to assess the neurobiology of pain-related thoughts and emotions, as well as treatment studies that assess the impact of integrative therapies such as cognitive-behavioral therapy, yoga, and acupuncture on pain-related outcomes in adults with chronic pain. The research group is also working in the area of predicting and preventing misuse of opioids by patients with persistent pain. Psychosocial processes such as catastrophizing and negative affect are strongly associated with opioid misuse, and cognitive-behavioral interventions appear to be effective in targeting these factors and enhancing compliance with recommended medication regimens. Collectively, the center hopes that these studies will illuminate some of the common mechanisms by which diverse non-pharmacologic therapies help to improve the quality of life for patients with chronic pain.

Funding: R21 DA041020: Opioid-induced changes in pain modulation; PCORI: A Comparative Effectiveness Randomized Controlled Trial of Mindfulness Meditation versus Cognitive Behavioral Therapy for Opioid-Treated Chronic Low Back Pain; R01AR064367: Brain mechanisms underlying CBT-related reductions in fibromyalgia
PI: Robert R. Edwards, Ph.D.
Email: rredwards@partners.org
Web page: http://research.bwhanesthesia.org/research-groups/prc/clinical/edwards

Selected Publications:

Center for Perioperative Genomics

The research programs within the Center are focused on exploring the genetic inputs into functional and structural heart disease, with a special focus on the perioperative environment. The Center is the over-arching structure for large-scale genetic studies that includes data and tissue resources for Investigators.

Current programs within the center include:

  1. The CABG Genomics Program, a two-institution study that provides patient data and genomics resources to the investigators. Since 2001, ~2,900 patients undergoing cardiac surgery have enrolled in the Program. Clinical data, patient outcomes, and DNA, buffy coat mRNA, plasma, and serum, are collected and stored for subsequent genotyping and measurement of circulating biomarkers. Specifically, CABG Genomics seeks to identify the relationships between genetic variation and major adverse cardiac events, bleeding and other patient outcomes after CABG surgery.
  2. The International Bicuspid Aortic Valve Consortium, a 26 institution consortium investigating the genetic etiology of bicuspid aortic valve disease. The consortium was started in 2011 and encompasses investigators from Europe, Canada and the U.S. The goals are to elucidate the genetic pathways involved in BAV etiology and the subsequent progression of aortic valve calcification by identifying genetic etiologies of BAV.
  3. The TRANSCRIBE study (Transcriptomic Analysis of Left Ventricular Gene Expression) aims to identify the genes expressed in response to acute myocardial ischemia, and the genetic modifiers of such gene expression.

Funding: R01HL098601 - Identification of genetic and molecular mechanisms of atrial fibrillation; R01HL114823 - Genetic etiology of bicuspid aortic valve disease; R01HL118266 - Genetics of gene expression in human left ventricular myocardium
PI’s: Simon Body, M.B.Ch.B., M.P.H. & J. Daniel Muehlschlegel, M.D., M.M.Sc.
Emails: sbody@partners.org & jmuehlschlegel@partners.org
Web page: http://research.bwhanesthesia.org/research-groups/cpg

Selected Publications:

Aging Neuroscience Laboratory

The Laboratory for Aging Neuroscience is focused on the aging brain and the role of baseline cognitive impairment, surgery and anesthesia in the development of postoperative delirium and postoperative cognitive dysfunction; two very a common and distressing source of postoperative morbidity in the elderly. To do so we use rodent models to study the molecular changes in the brain after surgery and anesthesia and preoperative and intraoperative variables in older surgical patients that may be associated with adverse outcomes.

Whether there is a relationship between the enduring cellular and molecular effects of general anesthesia in the aged brain and the postoperative cognitive morbidity observed commonly in elders after surgery and anesthesia remains to be determined but we have established collaborations with colleagues in geriatrics, neurology, psychiatry and inflammation to begin to address that question. Our hope is that better understanding of the impact of preoperative and perioperative variables on the neurobiology of the aged brain will ultimately translate into improved cognitive outcome after surgery and anesthesia in elders.

Funding: RO1AG048522 – Microglial mechanisms of postoperative CNS inflammation and cognitive decline; R21AG048522 - Preoperative cognitive screening in elderly surgical patients: feasibility and utility for predicting morbidity
PI’s: Gregory Crosby, M.D., M.S.A. & Deborah J. Culley, M.D.
Emails: gjcrosby@bwh.harvard.edu & dculley@bwh.harvard.edu
Web page: http://research.bwhanesthesia.org/research-groups/lan

Selected Publications:

Laboratory of Nanomedicine and Biomaterials

Research in the Laboratory of Nanomedicine and Biomaterials is focused on the development of novel nanotechnologies for medical applications. The team has pioneered design, engineering, and high throughput screening of multifunctional nanoparticle technologies for the treatment of cancers, inflammatory and immunological diseases. The targeted nanoparticle for the treatment of solid tumors, BIND-014, is in Phase II human clinical trials (ClinicalTrials.gov Identifiers: NCT01792479 and NCT01812746), marking the first-in-human testing of a targeted polymeric nanoparticle for cancer chemotherapy. A nicotine nanoparticle vaccine, SEL-068, has also entered the clinical trials for smoking cessation and relapse prevention, and the clinical translation of SEL-068 marked the first-in-human testing of targeted polymeric nanoparticle vaccine (ClinicalTrials.gov Identifier: NCT01478893).

Over the past 12 years, research in the Farokhzad laboratory has sought to develop robust engineering processes to accelerate translation of nanotherapeutics for clinical applications. At the same time, the team has advanced our fundamental understanding of the interface between nanomaterials and the biological system, all in order to aid in nanoparticle drug development. Currently, Dr. Farokhzad’s group has 11 postdoctoral fellows and visiting scientists, and 17 research assistants and technicians.

Funding: R01EB015419 - Development of FCRN-targeted nanoparticles for efficient oral delivery of insulin
PI: Omid C. Farokhzad, M.D., M.A., M.B.A.
Email: ofarokhzad@bwh.harvard.edu
Web page: http://farokhzad.bwh.harvard.edu

Selected Publications:

Brian Bateman / Division of Pharmacoepidemiology and Pharmacoeconomics

Brian Bateman’s research focuses on pharmacoepidemiology in pregnancy and the epidemiology of pregnancy related complications. His research is primarily conducted within the Division of Pharmacoepidemiology and is done in close collaboration with Krista Huybrechts and Sonia Hernandez-Diaz (from the Harvard School of Public Health). Topics of primary interest include the use of opioids during pregnancy and its consequences, the safety of cardiovascular medications in pregnancy, predictors of severe maternal morbidity and mortality, and medication safety in the perioperative period.

Funding: RO1 DA044293 - The impact of prescription opioid use on pregnancy outcomes, K08HD075831 - Comparative safety & effectiveness of antihypertensive medications in pregnancy, Lilly, Pfizer, Pacira, GSK
PI: Brian Bateman, M.D., M.Sc.
Email: BBateman@bwh.harvard.edu
Web page: http://www.drugepi.org/faculty-staff-trainees/faculty/brian-bateman/

Selected Publications:

Center for Perioperative Research (C.P.R.)

The mission of the Center for Perioperative Research is to facilitate research projects designed to test strategies that promote high quality perioperative care. We created a unique and innovative collaborative model of clinical and translational research led by Surgeon-Anesthesiologist teams designed to improve quality of perioperative care, realize cost savings, and foster education of the members of Surgery and Anesthesia Departments. Our research activities include clinical trials of pharmaceutical agents, monitoring, and equipment. Other recent projects have focused on understanding clinical risk factors for post-discharge surgical readmissions and reoperations using hospital and national outcomes data. Some of the projects involve investigation of the efficacy of informatics-based clinical decision tools, efficacy of perioperative (OR and Non-OR) efficiency interventions, and enhanced recovery after surgery (ERAS) pathways. We have performed analysis of quality metrics and patient outcomes using national databases to study patient mortality, care patterns, complication rates, and healthcare utilization. Recent work has focused on outcomes data from NSQIP, NIS, Medicare/Medicaid, NACOR and closed claims databases. Our recent patient safety-related research has been focused on emergency manuals, including a recent multi-institutional study funded by the Anesthesia Patient Safety Foundation. There is also an ongoing study on the preoperative goals of care discussions funded by the Foundation for Anesthesia Education and Research. The Center is currently working on a collaborative project with the medicine department to identify risk factors for opioid-related complications in hospitalized surgical patients.

Funding: Anesthesia Patient Safety Foundation; Foundation for Anesthesia Education and Research; Merck; Mallinckrodt; Medtronic
PI: Richard D. Urman, M.D., M.B.A., F.A.S.A. (Anesthesia), Co-Director: Edward E Whang, M.D., F.A.C.S. (Surgery)
Email: rurman@bwh.harvard.edu
Web page: http://www.brighamandwomens.org/Departments_and_Services/anesthesiology/services/cpmmi.aspx

Selected Publications: