Alfred L. Goldberg, PhD
Professor, Department of Cell Biology, Harvard Medical School
DF/HCC Program AffiliationCancer Cell Biology
Our laboratory studies the physiological regulation and molecular mechanisms of protein breakdown by the ubiquitin proteasome pathway in eukaryotic cells. A major focus is to elucidate the functioning of the 26S proteasome and especially the role of its regulatory ATPases in selectively delivering protein substrates to the 20S proteasome where they are degraded. One particular cancer-related interest is in the development of agents that block functioning of this pathway and may be useful in the clinic (e.g. Bortezomib, now used in treatment of Multiple Myeloma). Additional research efforts are focusing on the role of the ubiquitin proteasome pathway in disease states. A major goal is to understand the mechanism of how overall proteolysis in muscle is accelerated and causes muscle atrophy in various disease states (e.g. cancer cachexia). We are also attempting to understand the role of protein breakdown in immune surveillance (the role of the proteasome in generating MHC Class I antigenic peptides) and how cells selectively degrade misfolded protein as arise in various neurodegenerative diseases.
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