Ellen Gravallese, MD
Theodore Bevier Bayles Professor of Medicine and Chief, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School
President of the American College of Rheumatology
Recipient of the 2019 international Carol Nachman Award and the 2017 Stephen M. Krane Award from the American Society of Bone and Mineral Research
Ellen Gravallese, MD, is a graduate of Harvard College (AB) and Columbia University (MD). She completed her residency in internal medicine and pathology and fellowship in rheumatology at Brigham and Women’s Hospital (BWH) and performed postdoctoral research in the laboratory of Dr. Laurie Glimcher before joining the faculty of BWH. After many productive years, Dr. Gravallese was recruited as Professor of Medicine and Chief of Rheumatology at the University of Massachusetts Medical School, where she served for 13 years. She returned to BWH as Chief of Rheumatology, Inflammation, and Immunity. Dr. Gravallese is currently an Associate Editor at NEJM and is co-editor of the textbook Rheumatology. She has mentored dozens of graduate and medical students, residents and postdoctoral fellows, overseeing their training awards and leading them towards successful independent careers, and she lectures nationally and internationally.
Seminal research in Dr. Gravallese’s laboratory identified osteoclasts as the essential cells responsible articular bone erosion in RA. In paradigm-shifting work using RA synovial tissues, Dr. Gravallese identified that RANKL, the essential cytokine for osteoclast differentiation, was expressed by synovial fibroblasts and activated T lymphocytes within the RA synovially-derived tissues at the bone-pannus interface at sites of osteoclastic resorption of bone. To prove causality of osteoclasts as the agents of bone destruction, her laboratory collaborated to apply the serum transfer model of arthritis to mice deficient in RANKL, and therefore deficient in osteoclasts. This was the first work to demonstrate that osteoclast-deficient mice are protected from articular bone erosion but develop arthritis and cartilage destruction. Dr. Gravallese’s further studies highlighted the interplay of multiple cytokines with the ability to induce and/or synergize with RANKL to lead to bone destruction and promoted the initiation of the field of “osteoimmunology”. The RANKL pathway has subsequently been targeted to protect patients from systemic bone loss in many clinical settings. Dr. Gravallese’s laboratory also pioneered the use of needle biopsy of synovial tissue in clinical trials of RA to determine changes in gene and protein expression, a technique which is now the “gold standard” for clinical trials assessing novel therapeutics.
In addition to its impact on osteoclasts, Dr. Gravallese’s work on inflammation in the bone microenvironment in inflammatory arthritis has shown that osteoblast maturation and function is compromised, inhibiting bone repair. Her laboratory has showed that inhibitors of the Wnt signaling pathway, including members of the sFRP family, are expressed by cells within inflamed synovium and contribute to the inhibition of osteoblast function and bone formation at sites of erosion. She also recently completed a collaborative clinical trial in RA to assess the efficacy of intermittent PTH, an anabolic agent, in promoting the healing of articular erosions in RA.
The most current work from Dr. Gravallese’s laboratory focuses on the innate immune mechanisms recognizing cytosolic DNA and their roles in bone homeostasis and inflammation. Please see our Research to learn more about these research efforts.