Molecular chaperones are ubiquitously expressed proteins with wide-ranging functions in the folding and cellular translocation of a variety of proteins. Whereas these house-keeping functions are well recognized and have been the subject of intense investigation, it is now becoming clearer that chaperones are also co-opted in pathogenic cells to carry out disease-specific specialized roles. It is now believed that in pathogenic systems, chaperones abet transformation and allow for the blossoming of the disease phenotype.
Research in my laboratory aims to investigate and bring answers to several questions:
- What are the transformation-specific roles taken on by chaperones? How do they manifest?
- Can we understand and differentiate the disease abetting roles of chaperones from their house keeping functions?
- Can we discover pharmacologic modulators (chemical tools) that interact specifically with the disease-specific chaperone complexes (species)?
We use a chemical biology approach based on specific Hsp-targeted inhibitors and other chemical tools that we design and synthesize in our laboratory. Specifically, we develop chemical tools that target the disease-regulating but not the normal cell, house-keeping functions of the Hsps. These tools allow for the investigation of mechanisms refractory to other means, such as biochemical and genetic approaches, and provide the springboard for the development of therapeutics.