Prof. Jeffrey Brodsky holds the Avinoff Chair in Biological Sciences at the University of Pittsburgh.
Prof. Brodsky was born in Chicago, Illinois, and attended the University of Illinois where he received his bachelor's degree in Biochemistry, graduating magna cum laude with honors in 1985. He then entered the Biochemistry and Molecular Biology graduate program at Harvard University, receiving his PhD in 1990, and worked with Prof. Guido Guidotti on regulation of the sodium pump in the brain. Next, he moved to the University of California, Berkeley for post-doctoral research as an American Cancer Society Research Fellow and studied with Prof. Randy Schekman (Nobel Laureate, 2013), who pioneered the use of the yeast model to define how proteins are trafficked within the cell.
Prof. Brodsky joined the Faculty in the Department of Biological Sciences at the University of Pittsburgh in 1994 and was promoted to Associate Professor in 2000. In 2006 he was promoted to Full Professor and was awarded the Avinoff Chair. Prof. Brodsky’s work now focuses on understanding how misfolded proteins are recognized and destroyed in the cell, and how defects in protein architecture can be corrected using drugs and genetic approaches. Based on his work, he received the University of Pittsburgh Chancellor's Outstanding Research Award in the Junior Division in 1998 and the Chancellor’s Outstanding Teaching Award in 2008, as well as the Pitt Innovator Award in 2007.
In 2013, Dr. Brodsky was elected a Fellow of the American Association for the Advancement of Science (AAAS) and in 2022 he was again awarded the Chancellor's Outstanding Research Award (Senior Division), which was followed by elected membership in the American Academy of Arts and Sciences (2024). He also leads the Center for Protein Conformational Diseases on campus. Prof. Brodsky has served on the editorial boards of three journals, has published >250 scientific papers, holds several patents, and has acted as a scientific consultant for numerous disease foundations and biotech/pharmaceutical companies.
Our work focuses on understanding how misfolded proteins are recognized and destroyed in the cell, how molecular chaperones mediate protein quality control “decisions”, how cellular stress impacts protein homeostasis ("proteostasis"), and how defects in protein architecture can be corrected. Our early work contributed to the discovery of the endoplasmic reticulum associated degradation (ERAD) pathway, which we named, and ongoing studies are deciphering the mechanisms underlying this pathway in yeast, mammalian cell culture, and rodent models. The importance of ERAD is evidenced by the fact that >70 human diseases are associated with the pathway, and numerous ERAD substrates play vital roles in human physiology. To determine the molecular basis of these diseases and other protein conformational diseases, we express specific protein substrates in yeast, tissue culture, and rodent models, and characterize factors mediating their folding and disposal--and concomitant stress responses--using genetic, biochemical, cellular, and pharmacological tools. In parallel, biochemical assays are being developed in which distinct steps during ERAD and protein biogenesis can be reconstituted. New classes of small molecule modulators of chaperones and the ubiquitin-proteasome pathway have also been isolated and show efficacy in a range of disease models.
