We use the whole gamut of modern techniques -- molecular, cellular, biochemical, proteomic, genomic, bioinformatic -- to investigate the role of the transcription factor HNF4 in physiology and disease with particular emphasis on cancer and diabetes. In so doing, we aim to shed light on the molecular mechanisms of tissue-specific gene regulation, the dichotomy between cellular differentiation and proliferation, and the role of transcription regulation and alternative splicing and promoter usage in human evolution.
- Ligand Binding
- Identify the endogenous ligand for HNF4
Characterize the function of ligand binding
- HNF4 Isoforms
- Characterize the functional differences between the various HNF4 splice variants
Determine the physiological effects of those splice variants in different tissues using in vivo and in vitro models
- Post-translational modifications
- Identify and characterize the post translational modifications in HNF4
Identify the relevant modifying enzymes and signaling pathways
- Genome-wide Analysis of Nuclear Receptor Target Genes
- Use the latest tools in bioinformatics and genomics to identify all the HNF4 target genes in the human and mouse genomes
Use protein binding matrices and bioinformatics to develop a network of target genes for HNF4 and other nuclear receptors
We gratefully acknowledge past and present funding from a variety of state and federal agencies including the California Breast Cancer Research Coordinating Committee, the UC Toxic Substances Research and Training Grant, the American Heart Association, the National Science Foundation and the National Institutes of Health.