Dr. Darren F. Boehning
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Biochemistry and Molecular Biology
Our lab is interested in apoptotic cell death, and how this process is altered in cancer and neurodegeneration. One area of investigation concerns calcium channel activation during apoptosis. The inositol 1,4,5-trisphosphate receptor (IP3R) is a ligand-gated ion channel which releases calcium from ER stores. We and others have shown that the IP3R plays a critical role in apoptotic calcium release. Our current efforts are focused several related projects. One project investigates the molecular mechanisms leading to calcium release from the IP3R in response to activation of the Fas death receptor with relevance to lymphoma and autoimmunity. Another project is investigating a role for BRCA1, which is mutated in hereditary breast and ovarian cancer, as a pro-apoptotic protein and modulator of IP3R activity. These projects rely heavily on advanced live cell imaging techniques.
The second major focus of our lab is apoptotic signaling in neurodegeneration. We are investigating how the ubiquilin family of proteins contribute to the pathogenesis of Alzheimer’s disease and amyotrophic lateral sclerosis. Specifically, we have evidence that the ubiquilin proteins function as molecular chaperones in neurons preventing the aggregation of disease-relevant proteins. We are investigating how the activity of these proteins is altered during disease progression to affect neuronal proteostasis. These projects utilize biochemical and biophysical techniques to examine protein folding in vitro and in vivo.