We study protein quality control across translational models of cancer, cardiovascular disease and neurodegeneration with the goal of defining mechanisms of protein homeostasis and identifying therapeutic targets. Our unified approach is based on the realization that a single cellular machinery, the Hsp90/Hsp70 based chaperone machinery, controls the activity, turnover and trafficking of hundreds of client proteins, and as such plays a critical role in the pathogenesis of these varied disorders. Our goal is to define the mechanism by which this machinery triages unfolded or damaged proteins for degradation in order to develop strategies to achieve therapeutic benefits in disease.
All meetings begin at 1:30 pm
September 8, 2020 – No Meeting
October 13, 2020 – No Meeting
November 10, 2020 – No Meeting
December 8, 2020 – No Meeting
January 12, 2021 – Andrea Thompson – Zoom Link
February 9, 2021 – Mukesh Nyati – Zoom Link
March 9, 2021 – Matthias Truttmann’s Lab – Zoom Link
April 13, 2021 – Yoichi Osawa’s Lab – Zoom Link
May 11, 2021 – Andy Lieberman’s Lab – Zoom Link
June 8, 2021 – Mark Cohen – Zoom Link
Andrew Lieberman is the Gerald Abrams Collegiate Professor of Pathology and Director of Neuropathology along with being the Co-Director of the Protein Folding Diseases Initiative. His laboratory studies inherited neurodegenerative disorders with the goals of identifying therapeutic targets. They are particularly interested in targeting the Hsp90/Hsp70 based chaperone machinery to promote degradation of misfolded proteins.
Yoichi Osawa is the Warner-Lambert/Parke-Davis Professor in Medicine and Professor of Pharmacology. His laboratory studies the Hsp90 and Hsp70 chaperone machinery in protein quality control with a focus on the ubiquitination and regulation of NO synthases and P450 cytochromes.
Mark S. Cohen
Mark S. Cohen is Associate Chair in Surgery and Associate Professor of Surgery and Pharmacology, Director of the Medical School Pathway of Excellence in Innovation/Entrepreneurship, Innovation Chief for the U of M Cancer Center, and a Principal Investigator in the Translational Oncology Program. His translational/basic laboratory is focused on the development of novel cancer therapeutics as well as improved drug delivery strategies to enhance local/regional drug effect and lower toxicity. This work has focused on novel withanolides, novel selective HSP90 inhibitors, and innovative drug delivery strategies with hyaluronic acid and mimetic HDL nanoparticles for all types of solid tumor malignancies.
Andrea Thompson is a Clinical Lecturer in Internal Medicine and is co-mentored by David Ginsburg and Sharlene Day. Her research focuses on developing novel chemical tools that target non-enzymatic sarcomere proteins, also mutations in non-enzymatic sarcomere proteins which are the most common cause of genetic cardiomyopathies. Molecular chaperones play a central role in the regulation of these proteins and are important target to chemical modulation.
Matthias Truttmann is an Assistant Professor in Molecular and Integrative Physiology and a Research Assistant Professor in the Institute of Gerontology. His lab studies how post-translational protein modifications regulate chaperone function. In particular, they are interested in a novel modification, called AMPylation, which recently emerged as a key regulator of HSP70 chaperone activity.
Mukesh Nyati’s lab conducts research around understanding EGF-Receptor mediated signaling in tumors. We now know that the clinical effectiveness of kinase-targeted agents has been inconsistent, mainly because of the acquired resistance. It has been shown that EGFR has scaffold/allosteric functions in addition to tyrosine kinase activity. Therapies that induce protein degradation of EGFR remains effective in tumors that acquire resistance to tyrosine kinase inhibitors. Based on our current understanding of TKI resistance and EGFR dimerization we are developing new therapeutic strategies targeting the intracellular dimerization interface of EGFR to induce protein degradation as a potential therapy option for EGFR-driven cancers.