A lectureship was established to honor the memory of Joseph Larner, who served as Professor and Chair of the Pharmacology Department for many years. During his time as Chair he recruited and mentored numerous successful faculty, including Al Gilman. He continued to be an inspiration to everyone who knew him, especially our graduate students, who were in awe of his energy and enthusiasm as he kept up his science and maintained an active departmental presence well into his 90s. In addition to honoring Dr. Larner’s memory, the goal of this lectureship is to highlight exciting new advances in an area that held great interest for him: the pervasive role of metabolism/cell signaling in human disease.

About this year's speaker:

Hosted by Thurl Harris and Michelle Bland, Michael Murphy is a Professor of Mitochondrial Redox Biology and Programme Leader at the MRC Mitochondrial Biology Unit at the University of Cambridge, UK

Dr. Murphy's Research Interests-

Mitochondrial dysfunction

Reactive oxygen species (ROS) produced by mitochondria cause oxidative damage that impairs the ability of mitochondria to make ATP and to carry out their metabolic functions. They may participate also in cellular redox signalling pathways.

One important aspect of our work is to investigate how oxidative damage to mitochondria contributes to human pathologies. We have worked out a way of targeting small bioactive molecules, such as antioxidants, to mitochondria in order to counter the effects of ROS and to examine the effects of doing so at cellular and whole animal levels. The bioactive molecule is attached chemically to a lipophilic cation such triphenylphosphonium. These cations accumulate selectively, first in the cytosol, driven by the plasma membrane potential, and then several-hundred fold in the matrix of mitochondria, driven by the membrane potential across the inner membrane.

A second important aspect is to determine whether and how mitochondrial ROS alters the activities of proteins in putative signalling and protective pathways by reversibly modifying the redox state of critical protein thiols in mitochondria. We use a range of free radical and proteomic approaches to identify the proteins involved, and to identify the cysteine residues and any redox modifications.

Finally, we take this information and use it to rationally design potential therapies for diseases that arise from mitochondria dysfunction. Currently our main focus for therapy is the ischaemia/reperfusion injury that arises from stroke and heart attack.