Dr.

Holly A. Ingraham

University of California, San Francisco
Area
Biological Sciences
Specialty
Medical Sciences
Member Since
2019

Research unraveled molecular events controlling endocrine tissue development. Demonstrated that the orphan nuclear receptor, Steroidogenic Factor 1 (SF-1), is a master regulator of the hormone MIS, thereby controlling male sexual differentiation. Envisioned gene dosage of SF-1 would have major consequences for endocrine tissue development, a hypothesis now validated by the large cohort of human SF-1 heterozygous mutants exhibiting endocrine disease. Used SF-1 to examine how orphan nuclear receptors are regulated by atypical phospholipid ligands or by post-translational modifications (PTM). Showed that sumoylation of SF-1 is critical for normal endocrine organogenesis, providing first in vivo example of how this PTM fine-tunes gene expression. With collaborators, solved the crystal structures for ligand binding domains of SF-1 and the closely related receptor, Liver Receptor Homologue-1 (LRH-1), leading to unexpected identification of phospholipids as physiologic ligands for these two nuclear receptors. Showed that nuclear lipid kinases and phosphatases directly remodel SF-1-bound phospholipids, illuminating a novel lipid-based signaling pathway for controlling gene expression.

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