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    We are broadly interested in programs that regulate endocrine and neuroendocrine tissue development. Our research focuses on NR5A nuclear hormone receptors because of their critical roles in endocrine organogenesis and metabolism. After showing that phospholipids serve as NR5A ligands we found thsimilar to plasma membrane signaling by PIP2 and PIP3, nuclear PI3-kinases and -phosphatases are able to act on the exposed-bound phospholipid headgroup and modulate receptor activity, illustrating how this class of transcription factor could be used to decode nuclear lipid signaling.
    NR5A receptors are also regulated by sumoylation, and as such are ideal models for understanding how this PTM regulates gene expression. Our recent study established that SUMO-less SF-1 mice exhibit inappropriate activation of SUMO-sensitive genes involved in cell specification and proliferation. Using a gene-expression HTS, we have identified a drug that ablates NR5A sumoylation in cells. Such leads may prove useful for targeting metabolic diseases and cancers.
    We also study the development of a neuroendocrine center, the
ventromedial hypothalamus (VMH), which controls metablism and reproduction. Using mouse genetics we mapped efferent projections from this regin, and have recently discovered that neurons in the VMHvl region control an estrogen-responsive female-specific circuit of physical activity.


Recent Publications

         

Cheung, C., Kurrasch, D.M., Liang, J. and H.A. Ingraham, Genetic Labeling Of SF-1 Neurons Reveals VMH Circuitry Beginning At Neurogenesis And The Emergence Of A Separate Non-SF-1 Neuronal Cluster In The Ventrolateral VMH J Comp Neurol 2013 Apr 15;521(6):1268-88, PMID: 22987798(2012).PDF

Blind, R.D., Suzawa, M. and H.A. Ingraham, Direct modification and regulation of the nuclear protein-lipid complex NR5A1-PIP2 by the PI3-kinase IPMK. (Cover and Podcast) Science Signaling 2012 Jun 19;5(229) PMID: 22715467 (2012).PDF

Lee, F.Y., Faivre, E.J., Suzawa, M., Lontok, E., Ebert, D., Cai, F., Belsham, D.D. and H.A. Ingraham,, Eliminating SF-1 (NR5A1) Sumoylation In Vivo Results in Ectopic Hedgehog Signaling and Disruption of Endocrine Development. (Cover, Preview, and Podcast), Developmental Cell 21:315-327 (2011). PMCID: PMC3157481 PDF


Holly Ingraham, Ph.D. - holly.ingraham@ucsf.edu
Professor and Associate Vice Chair
Cellular and Molecular Pharmacology
Herzstein Distinguished Investigator
1550 4th Street, Rock Hall 284E, San Francisco, CA 94143

Lab Phone: 415-476-3401
Office Phone: 415-476-2731


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