Regina Murphy

Title: Smith-Bascom Professor of Chemical and Biological Engineering
Office: University of Wisconsin-Madison

Homotypic and Heterotypic Interactions in Amyloid Protein Networks

Abstract: Amyloid protein deposits are strongly associated with the pathology observed in Alzheimer's disease, senile systemic amyloidosis, Parkinson's disease, and other degenerative disorders. Although the proteins in each disease differ in sequence and native fold, and all have different normal biological functions, all can be triggered to misfold and self-associate into insoluble aggregates of cross-beta structure and fibrillar morphology. Because these different proteins, upon misfolding, adopt similar conformations, we wondered whether they could interact heterotypically as well as homotypically. The biological relevance of heterotypic interactions is hinted at by studies which show that transgenic mice, engineered to express large quantities of the Alzheimer-related protein beta-amyloid, spontaneously upregulate expression of transthyretin, a transport protein that is the primary component of amyloid deposits in senile systemic amyloidosis. Moreover, transthyretin upregulation protects transgenic mice against neuronal damage that is otherwise caused by beta-amyloid. This observation suggests that, while homotypic interactions are pathological, heterotypic interactions between amyloidogenic proteins may actually be protective. In this talk we will discuss our efforts to define the molecular basis for heterotypic interactions between beta-amyloid and transthyretin, and to develop novel therapeutic compounds based on this understanding.

Regina Murphy, Smith-Bascom Professor of Chemical and Biological Engineering at UW-Madison, received her PhD in Chemical Engineering from MIT. She has received the Chancellor's Distinguished Teaching Award, and is a Fellow of AIMBE. Her favorite memories of Ed Lightfoot include eating at Wah Kee's noodle shop and looking for eagles along the Wisconsin River in Sauk Prairie. Fun facts: Regina Murphy played varsity softball as an undergraduate and continues to play recreationally. She started running about five years ago and has now competed in several 5Ks, 10Ks, and half-marathons; her proudest achievement is a sub-two hour time and third place age-group medal at the Tyranena Half Marathon. The scariest thing she has ever done in her life was to play "Chaconne on Two Cabbages" at Bob Bird's 90th birthday celebration - she is glad that at Ed's 90th all she is doing is giving a talk!