Patrick H. Thibodeau, Ph.D.
Research Interest: Using structural, molecular, and biochemical approaches, my lab focusses on studying membrane protein structure-function relationships and the biosynthesis of these complex protein machines.

Transmembrane proteins establish the specific environments of cellular compartments separated by membranes. The proper expression and function of these proteins are critical to establishing the correct environmental conditions of these cellular compartments. ATP-Binding Cassette (ABC) transporters comprise a large superfamily of multi-domain proteins that regulate a variety of processes across cellular membranes. Mutations within these proteins result in human disease, such as cystic fibrosis and hypercholesterolemia, and altered expression of these proteins contributes to drug resistance in cancer. These transporters facilitate the movement of a variety of substrates from single ions (CFTR), cholesterol (ABCG5, ABCG8) and small molecules (Pgp, MDR) to large bacterial proteins (Type I secretion). My research focuses on the structure and function of these ABC transporters and the proteins that regulate and control their activity. First, using bacterial ABC transport systems, structure-function and mechanistic studies can be accomplished to better understand the reaction cycles associated with substrate translocation. Specifically, the protease secreting ABC-transporter systems, implicated to play a role in the pathogenesis of E. coli and P. aeruginosa, will be utilized to study the structure and function of these secretory systems using biochemical and structural approaches.

Second, using the eukaryotic transport systems (CFTR, ABCG5 and ABCG8), biochemical and cell biological approaches will be used to identify the cellular systems that monitor the structure and regulate the function of these proteins. Previous work has demonstrated that mutation to these proteins can cause improper folding and retention in the ER and/or destabilization of the protein at the plasma membrane. Using biochemical, cell biological and genetic approaches, the cellular systems that are associated with monitoring the structure of these transporter systems will be identified and characterized.

Recent Publications: