Mark Hochstrasser

Biosketch

Dr. Hochstrasser is the Eugene Higgins Professor and former Chair of the Department of Molecular Biophysics & Biochemistry at Yale University. He received his BA in Biology and German from Rutgers University (New Brunswick, NJ). He went on to do his PhD research on nuclear chromosome organization at the University of California, San Francisco and then initiated his studies of protein degradation as a postdoctoral fellow at MIT. In 1990 he started his own research group at the University of Chicago; he moved to Yale University in 2000. Besides the NAS, Dr. Hochstrasser is a member of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, and the Connecticut Academy of Science and Engineering.

Research Interests

Dr. Hochstrasser’s initial focus was on determining the mechanisms of degradation for endogenous short-lived regulatory proteins using the model organism Saccharomyces cerevisiae. The studies helped define key features of the ubiquitin-proteasome system, the central protein degradation system of all eukaryotes. One target of study was a ubiquitylation pathway that turned out to target both soluble intranuclear proteins and transmembrane proteins in the endoplasmic reticulum and nuclear envelope. Another early investigation identified a yeast deubiquitylating enzyme (DUB) that was crucial for maintaining cellular ubiquitin levels and was related to a human oncoprotein. Genetic analysis of this DUB led to the identification of proteins (now called ESCRT factors) connecting ubiquitin recycling from ubiquitin-modified membrane proteins in endosomes to their trafficking to the vacuole (lysosome). Other studies focused on characterization of the proteasome, particularly its chaperone-assisted in vivo assembly from at least 33 different polypeptides. Hochstrasser’s group also discovered the highly conserved proteases that remove the ubiquitin-like protein SUMO from substrates. More recent work led to the mechanistic characterization of an important reproductive manipulation by the obligate intracellular bacterium Wolbachia, which is used worldwide as a biocontrol against disease-vectoring insects. One mechanism involves a DUB toxin delivered by sperm; another utilizes a nuclease toxin.