Assistant Professor, Department of Medicine, UCSF
My research has focused on the study of the receptors that regulate cells in the innate immune system. We previously examined receptors on natural killer cell lymphocytes, but currently focus our work on similar receptors on osteoclasts. Our research is a major area of interest in the recently defined field of study termed osteoimmunology. Osteoimmunology is defined as a cross disciplinary field to integrate studies of the immune system and studies of bone and better define the interactions between these systems.
Osteoclasts are the only bone resorbing cell, and are derived from monocyte/macrophage precursors. Osteoclast differentiation was previously demonstrated to require the stimulation by specific cytokines (RANKL and MCSF), but the roles of other immune receptors has only recently been investigated. Our studies demonstrated that innate immune receptors that utilize ITAM or immunoreceptor tyrosine based activation motif signals are also critical regulators of osteoclast development and function, during normal bone development and homeostasis. We demonstrated that mice deficient in the ITAM adapter signaling chains DAP12 and FcR? are severly osteopetrotic due to defective osteoclast differentiation and function. Our studies suggest that osteoclasts are regulated much like other innate immune cells such as natural killer cells, macrophages and dendritic cells and should be considered an integral part of the innate immune system. I have chosen to focus the recent work in my laboratory on osteoimmunology since the role of innate immune receptor regulation in the bone in an understudied area, and inflammatory bone loss is of direct importance in rheumatologic diseases. My overall goal is to examine the role of innate immune receptors in autoimmune disease states and bone remodeling, which best integrates my research interests with my clinical subspecialty work. Until recently we have examined only murine osteoclasts and mouse models of disease, but we have initiated work on murine ostoblasts and human osteoclasts in addition and have begun translational studies on osteoclast precursors in rheumatoid arthritis patients.
Swarthmore College, Swarthmore, PA, B.A., 1981, Biology
Yale University School of Medicine, New Haven, CT, M.D., cum laude, 1986, Medicine
Intern and resident, Department of Internal Medicine, UCSF, San Francisco, CA, 1986-1989
Rheumatology Fellow, Div. Rheumatology, Johns Hopkins U., Baltimore, MD, 1990-1991
Rheumatology Fellow, Div. Rheumatology, UCSF, San Francisco, CA, 1991-1994