Towards Drugging Mitochondrial Fission Protein Fis1 in Diabetic Endothelial Dysfunction – Blake Hill, PhD

Towards Drugging Mitochondrial Fission Protein Fis1 in Diabetic Endothelial Dysfunction – Blake Hill, PhD

May 16, 2018 @ 12:00 pm – 1:00 pm
Froedtert - WI Diagnostics Lab Building, 2nd floor, Ob-Gyn conference room #252
Taylor Anglin
(414) 805-5695

Presented by

Blake Hill, PhD
Department of Biochemistry
Medical College of Wisconsin

Dr. Hill’s Research

Defects in mitochondrial fission and fusion cause or contribute to human diseases including cancer, neuropathies, cardiomyopathies, and even death. Our goal is to understand molecular basis of these defects in order to identify new therapeutic routes for these diseases.

We determine how proteins interact with other biological macromolecules to control these basic membrane fission and fusion processes in healthy, diseased, and dying cells. We strive to understand these interactions on a physicochemical level, with an eye for gleaning universal principles of protein chemistry including interactions with membrane bilayers that are fundamental to a wide variety of cellular processes.

A key feature of some proteins that affect mitochondrial homeostasis is the structural transformation from soluble to membrane-bound conformations, a phenomenon referred to as amphitropism. Associating with, or dissociating from, a membrane (i.e. amphitropism) has significant functional consequences for numerous biological processes: it can affect enzymatic activity (CCT, PLC), can promote changes in organelle and cell morphology (MinD, dynamins), or can act as a regulatory switch in various signaling cascades (PKC, ESCRTs). However, neither what drives proteins to reversibly interact with membranes nor how this function controls biological outcomes are clearly understood. These interactions are likely governed by evolutionarily conserved mechanisms that are still being determined and is one focus of our efforts.

Towards these goals, we use a wide range of tools including genetic, cell biological, biochemical, and biophysical methods including NMR spectroscopy and x-ray crystallography for protein structure determination.

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