Alfred Goldberg

Dr. Goldberg, a Professor of Cell Biology at Harvard Medical School, has been on its faculty his entire academic career. He received his AB degree and PhD in Physiology from Harvard University, after attending Cambridge University as a Churchill Scholar and Harvard Medical School. His important discoveries have concerned the mechanisms and regulation of protein breakdown in cells. His laboratory first demonstrated the non-lysosomal pathway for protein breakdown, now termed the ubiquitin-proteasome pathway. They also discovered the involvement of the 26S proteasomes in this process and the ATP-dependent proteases responsible for proteolysis in bacteria. Also of wide impact have been his studies showing that this pathway is critical in clearance of misfolded proteins, in muscle atrophy, and in antigen presentation to the immune system. He and his colleagues introduced the proteasome inhibitors widely used as research tools, and he initiated development of the proteasome inhibitor, Bortezomib/Velcade, now used worldwide to treat multiple myeloma. Goldberg’s research accomplishments have been recognized with many distinguished prizes. He is also a Fellow of the American Academy of Arts & Sciences and a member of the National Academy of Medicine, and has received honorary degrees from Cold Spring Harbor Laboratories, University of Maastricht and University of Barcelona.

Research Interests

Dr. Goldberg’s laboratory has long been a center for research into the biochemical mechanisms and physiological importance of protein breakdown in cells in normal and pathological states. The major focus of their present research concerns the detailed mechanisms by which the 26S proteasome catalyzes the rapid degradation of ubiquitinated proteins. One goal of these studies is to understand how the ubiquitin proteasome pathway selectively degrades misfolded, aggregation-prone proteins as cause the major neurodegerative diseases, and to find methods to activate this degradative process in order to enhance the clearance of such potentially toxic proteins. Other studies are investigating how the overall rate of protein degradation is accelerated in certain pathological conditions, such as muscle atrophy as results from disuse, denervation, or various systemic disease (especially, cancer). His laboratory is also exploring how cells respond to proteasome inhibitors and compensate for decreased proteasome function by inducing the production of new proteasomes or activating autophagy. Another long term interest of Dr. Goldberg’s lab concerns the simpler ATP-dependent proteases that eliminate misfolded proteins in bacteria. Ongoing studies are attempting to identify selective inhibitors of these novel enzymes, which might be useful as antimicrobial drugs, especially for treatment of tuberculosis.