Biochemistry Graduate Seminar
*Wednesday, November 18
*Lecture at 4:30 p.m. in Ackert Hall 120
Coffee at 4:15 p.m. in Chalmers 168
Samuel A Molina
The Mechanism of Cellular Resistance to Hypoxia in Retinoblastoma
Hypoxia is defined as a sub-physiological level of oxygen present in a tissue. Molecular oxygen is necessary for aerobic metabolism in the vast majority tissues found in the body. In normal tissue, prolonged hypoxia results in impaired metabolic function leading to cell death and tissue necrosis. However, specialized tissues subjected to chronic hypoxia function normally and resist cell death, e.g. bone tissue and tissues in the eye such as the lens. Diseased states such as early tumor growth, diabetic retinopathy, tissue infarction, and aberrant angiogenesis all have a hypoxic component in common. The hypoxic response is primarily controlled through the heterodimeric transcription factor Hypoxia Inducible Factor 1 (HIF-1). Known HIF-1 up-regulated families of genes include glucose transporters, glycolytic enzymes, and proteins involved in development and wound healing. We are interested in finding the role that the gap junction proteins, the connexins, play in hypoxia.
Previous work in the Takemoto lab has shown that Connexin 46 (Cx46, GJA3) can mediate hypoxia resistance in vitro and in vivo in the lens and in early breast tumors. However, the mechanism of connexin-mediated hypoxia resistance is unexplored to date. By using the eye as a model system, questions about the mechanism of Cx46-mediated hypoxic resistance will be answered. My project has three aims relating to retinal hypoxia and retinoblastoma, specifically the function of Cx46 in conveying resistance to hypoxia. The questions to be answered are: 1) Is Cx46 up-regulated at the gene expression level during hypoxia and, if so, to what extent? 2) How is the structure of Cx46 related to its function in conveying resistance to hypoxia? 3) Is Cx46 knockdown a plausible therapy for the treatment of retinoblastoma? The experimental rationale and approach will be outlined in the presentation, along with current data supporting the rationale.
*Please note date and place change.