Jeffery W. Kelly (Scripps Research Institute)

The event will start on: Wed, Feb 20, 2013 | 12:00 pm
Location: Lewis Thomas Lab, 003 | Washington Road

MolBio Seminar Series


Jeffery W. KellyJeffery W. Kelly
Professor of Chemistry
Departments of Chemistry and Molecular and Experimental Medicine,
The Scripps Research Institute
Skaggs Institute of Chemical Biology



Seminar Topic

Biological and Chemical Approaches to Adapt Proteostasis to Ameliorate Protein Aggregation Diseases 

The cellular protein homeostasis, or proteostasis network, regulates proteome function by controlling ribosomal protein synthesis, chaperone and enzyme mediated protein folding, protein trafficking, protein degradation and the like. Stress responsive signaling pathways match proteostasis network capacity with demand in each subcellular compartment to maintain cellular homeostasis. The beginning of the seminar will focus on how the proteostasis network can be adapted through unfolded protein response arm-selective signaling to alleviate gain-of-toxic-function diseases where excessive secretion of misfolding and aggregation of proteins leads to the amyloid diseases. The second part of the seminar will focus on a chemical strategy to achieve protein homeostasis, wherein small molecule kinetic stabilizers produced by structure-based drug design are employed to halt the progression of peripheral neuropathy in the human disease familial amyloid polyneuropathy linked to transthyretin amyloidogenesis. I will explain how delineating the molecular mechanism of transthyretin aggregation linked to pathology led to a regulatory agency approved drug. Since this is the first pharmacologic evidence supporting the amyloid hypothesis, the notion that protein aggregation causes degeneration of the heart and the nervous system, the last part of the seminar will focus on what we have learned about the etiology of these diseases vis-à-vis a successful clinical trial.

Research Lab

 Information Forthcoming


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Hosted by: Manuel Llinas, Molecular Biology

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