Medical Student Research Fellowship for Summer 2003

Mentor: Joseph A. Hill, M.D., Ph.D.
Department: Internal Medicine/Cardiology
Room number: NB11.200
Mail Code: 8573
Phone number: 214-648-1400
E-mail: joseph.hill@utsouthwestern.edu
Project title: Forkhead Transcription Factors in Cardiac Hypertrophy

Human subjects IRB approved project number (where applicable): None

Animal subjects IRB approved project number (where applicable): 0973-02-02-1

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Animal-based research
APN# 0973-02-02-1

Brief Description of Project:

Background: Forkhead transcription factors are a major target of insulin signaling and are known to plan a role in cell survival and proliferation. Their role in hypertrophic growth of the heart is unknown.
Hypothesis: Nuclear translocation of forkhead transcription factors occurs in the setting of hypertrophic stress.
Methods: A GFP-tagged FOXO1 molecule will be engineered and transfected into cultured cardiomyocytes. After exposure to hypertrophic stimuli (angiotensin II, endothelin-1), evidence of nuclear localization of the protein will be ascertained by fluorescence microscopy. The role of active nuclear export will be determined using leptomycin D.
Significance: Evidence of FOXO1 translocation to the nucleus would suggest that these molecules mediate aspects of the transcriptional regulation of hypertrophy.

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