Leaders in Research

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Matthew P. Frosch, MD, PhD Associate Professor of Pathology Massachusetts General Hospital Harvard Medical School Matthew P. Frosch, M.D., Ph.D. Dr. Frosch’s intellectual attention was first directed at basic cellular functions of the nervous system during his education in the MD-PhD program at Harvard. As a graduate student in biophysics, he studied GABA-activated channels using patch clamp methods. After completing this program, Dr. Frosch then received training in anatomic pathology and neuropathology. This allowed him to expand both his intellectual and clinical horizons to include disease processes. During the neuropathology portion of his training, and continuing to the present time, Dr. Frosch began to examine the brains of patients with Alzheimer disease in order to confirm the ante-mortem diagnoses. His interest in the neuropathologic issues of dementing illnesses has led him to direct his research efforts at the biology underlying Alzheimer disease. Dr. Frosch continues to serve as the diagnostic pathologist associated with the Brain Donation Program of the Center for Neurologic Diseases at Brigham and Women’s Hospital, and to play a role in the NIH-funded ADRC brain bank at Massachusetts General Hospital. He has also developed, through these experiences, a series of clinicopathologic collaborations with investigators in the Laboratory of Higher Cortical Functions at Brigham and Women’s Hospital, which focuses on the clinical study of individuals with dementia and subsequent pathologic study of brain tissue for them. While many clinician-investigators who focus on neurologic illnesses come from disciplines other than neuropathology, Dr. Frosch has found the path he chose to be extremely satisfying. Although partially removed from the patient-doctor relationship, he finds that the doctor-doctor relationships that underlie the effective practice of diagnostic neuropathology are rich and rewarding. The consequences of his diagnoses for patients and their families are often brought home to him when he discusses autopsy findings with family members who requested study of their relative with a dementing illness. Dr. Frosch feels that his attempt to bridge the worlds of basic science, clinical neuropathology and aging research are relatively uncommon, and brings with it the potential to make significant contributions in both arenas. His clinical involvement in the diagnosis of dementing illness has carried over to his bench research activities. Although his graduate training was as a cellular electrophysiologist, Dr. Frosch has acquired the skills necessary to function as a molecular biologist. He has combined these with his histologic and pathologic training to be able to approach human disease with a wide perspective. Over the past few years, in part with support from the American Federation for Aging Research and from the National Institute on Aging, Dr. Frosch has generated a series of transgenic mice which produce various forms of presenilin-1 and more recently, presenilin-2. These animals are now being used in experiments with a wide variety of collaborators to try to determine the role of this protein in normal neuronal cell functioning and the consequences of mutations in the protein. The Beeson award will allow him to continue to pursue these studies and to expand these lines of investigation, particularly as regards the interaction of estrogen with other processes involved in the pathogenesis of Alzheimer disease.

Primary Research (for Beeson Program): Estrogen And Alzheimer Disease: