Medical Student Research Fellowship for Summer 2007

Mentor: Joseph A. Garcia, MD,PhD
Department: Internal Medicine
Room number: NB10-216
Mail Code: 8573
Phone number: 214-648-1646
E-mail: joseph.garcia@utsouthwestern.edu
Project title: Integrative Studies of Mice Lacking Hypoxia Sensing Transcription Factor 2a
Animal subjects IACUC approved project number (where applicable): APN 0896-06-06-3

Project Type: animal-based research, basic research

Brief Description of Project:
Hypoxia inducible factor 2 ?lpha (HIF-2?) is a transcription factor that activates a number of target genes in response to lowered tissue oxygen conditions (hypoxia) and other environmental stresses. HIF-2a has unique target genes that define its primary biological role in vivo. Adult mice that globally lack HIF-2a exhibit multiple organ pathology, metabolic abnormalities, and increased oxidative stress, a constellation of findings found in clinical mitochondrial disease states. A primary cause of mitochondrial dysfunction in HIF-2a null mice is due to ineffective induction of genes whose products are essential for the cellular response to oxidative stress. A second cause of pathology in HIF-2a null mice is due to ineffective induction of erythropoietin that results in impaired hematopoietic development. A third consequence of HIF-2a deficiency is impaired retinal vascular development; mice completely lacking HIF-2a have markedly impaired retinal vascular and are functionally blind. It is our belief that HIF-2a is a prime regulator of protective cellular responses to environmental stresses encountered during stroke, myocardial infarction, and other ischemic injury states. Our ongoing efforts are focused on testing these hypotheses. We are currently defining other affected aspects of the HIF-2a deficient state, additional physiologic roles of HIF-2? in the adult mouse, and molecular mechanisms underlying HIF-2? function.

Previous Research Activities or Publications with Medical Students:
Mentor summer, 2004 for Edgar Bedolla, MSII

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