Alfred L. Goldberg, Ph.D.

Professor of Cell Biology
Harvard Medical School

Dr. Goldberg, a professor of cell biology at Harvard Medical School, has been on the faculty of that institution for nearly his entire academic career. His important discoveries have concerned the biochemical mechanisms and physiological regulation of protein breakdown in cells and the importance of this process in human disease.  His laboratory first demonstrated the non-lysosomal ATP-dependent pathway for protein breakdown, now termed the ubiquitin-proteasome pathway. They first demonstrated the involvement of the 20S and 26S proteasomes in this process and discovered the ATP-dependent proteases responsible for protein degradation in bacteria and mitochondria.  Also of wide impact have been Dr. Goldberg’s studies showing that the ubiquitin proteasome pathway is critical in the clearance of misfolded proteins and in muscle atrophy seen in many disease states as well as in antigen presentation to the immune system.  He and his colleagues also first introduced proteasome inhibitors now widely used as research tools, and he initiated the development of the proteasome inhibitor, Bortezomib/Velcade, now widely used in the treatment of multiple myeloma.

Dr. Goldberg received his AB degree and his Ph.D. in Physiology in 1968 from Harvard University, after attending Cambridge University (as a Churchill Scholar) and Harvard Medical School.  Dr. Goldberg’s accomplishments have been recognized with many distinguished prizes, including the Novartis-Drew Award, Severo Ochoa Award (New York University), Knobil Prize for Medical Research (Univ Texas, the Gabbay Award for Biotechnology and Medicine (Brandeis University), Norman Alpert Prize for Medical Research (Harvard), and Ernest Beutler Prize for Basic Research (Amer Hematology Soc.). He is a fellow of the American Academy of Arts & Sciences and a member of the National Academy of Sciences and the National Institute of Medicine. He has received honorary degrees from Cold Spring Harbor Laboratories, the Univ of Maastricht (Netherlands) and Univ. of Barcelona (Spain) and is among the 1% most cited authors in the life sciences.

Funded Research

Project Description Researchers Funding
Activation of the 26S Proteasome for the Treatment of Alzheimer’s Disease

It has been widely assumed that rates of degradation of proteins by the ubiquitin-proteasome system (UPS) are regulated solely at the ubiquitination step. We recently discovered a novel biochemical mechanism, proteasome phosphorylation, that cells utilize to enhance their capacity to degrade misfolded proteins, such as mutant tau and phospho-tau (p-tau). We have shown that the 26S proteasome’s capacity to degrade ubiquitinated proteins is enhanced in cells and mouse brains by agents (e.g.

2016 to 2017

$300,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
Hyoung Tae Kim, Alfred L. Goldberg, The deubiquitinating enzyme Usp14 allosterically inhibits multiple proteasomal activities and ubiquitin-independent proteolysis, Journal Of Biological Chemistry, 292(23), 9 Jun 2017, 9830-9839
Galen Andrew Collins, Alfred L. Goldberg, The Logic of the 26S Proteasome, Cell, 169(5), 18 May 2017, 792-806