The Department of Biochemistry's weekly BCH 252 seminar series is presented this week by:

Dr. Dieter Wolf, Tumor Initiation and Maintenance Program, Sanford Burnham Prebys. Medical Discovery Institute

Seminar Title: "The making and breaking of mitochondria in health and disease"

Research Description: Research in Dr. Wolf’s laboratory focuses on basic mechanisms of protein and energy metabolism, their role in tumorigenesis, and their utility as cancer drug targets. The work has concentrated on conserved pathways regulating protein homeostasis and associated stress response pathways. These lines of investigation are pursued in human cell lines as well as in genetic models ranging from yeast to the mouse.

Recent efforts have focused on the role of eukaryotic translation initiation factor eIF3 in the control of mitochondrial biogenesis and cancer metabolism. Upregulation of eIF3 subunits is frequently observed in human cancers but its function remains poorly understood. Recent findings by the Wolf lab suggest that eIF3 controls mitochondrial biogenesis by promoting the synthesis and co-translational targeting of mitochondrial proteins. The studies revealed a novel function of eIF3 in boosting early ribosomal elongation speed, and loss of eIF3 results in defective protein synthesis and abnormal mitochondrial and lysosomal physiology in cells and animals.

A second topic of the Wolf lab is the development of small molecules targeting mitochondrial respiration as novel cancer therapies. Dr. Wolf’s lab identified mitochondrial inhibition as a novel drug target pathway in drug-resistant prostate cancer. The SMIP004 series of compounds potently inhibit the growth of prostate cancer xenografts in mice with no obvious toxicity. In recent work, Dr. Wolf’s lab identified the molecular target of SMIP004 and the compound’s detailed mechanism-of-action thus setting the stage for further preclinical development of a SMIP004-based treatment by medicinal chemistry and pharmacology.

Search Chair: Dr. Stephen Spindler; stephen.spindler@ucr.edu