Holly Ingraham, PhD

Hertzstein Distinguished Investigator
Professor & Associate Vice Chairman
Department of Cellular and Molecular Pharmacology
+1 415 476-3401
Research Overview: 

Our current biological interest lies in the development of a neuroendocrine center, the ventromedial hypothalamus (VMH), which functions as a central relay station to control both metabolic homeostasis and reproductive behavior. Because the hypothalamus remains poorly defined at a molecular level, we used gene profiling to identify novel genes that mark subsets of neurons within this brain region ( Kurrasch et al.2007). Presumably these markers participate in VMH development and function – the importance of these candidate genes is now being tested using standard molecular biology and mouse genetics. In addition with H. Baier's lab at UCSF we used a forward genetic screen in zebrafish and found 5 mutants disrupted in early hypothalamic patterning (Kurrasch et al., 2009). We are now asking how environmental factors influence the development and formation of the VMH. Indeed we recently showed that the widely used herbicide atrazine activates endocrine gene networks. This study was published in PloS One (Suzawa and Ingraham, 2008). Our paper was discussed on Talk of the Nation NPR’s Science Friday - May 9th, 2008 and selected by the Faculty 1000 of Biology as a Must Read paper.

We also study how a group of nuclear hormone receptors are activated, in particular members of the NR5A subfamily. NR5A receptors are critical for development and function of the endocrine system. In the last several years our lab used a structural approach to show that phospholipids can serve as ligands for NR5A1 nuclear receptors, such as SF-1 or LRH-1. We are now determining how these phospholipids ligands affect receptor activity. As with many transcriptional regulators, NR5A receptors are also richly modified by posttranslational events including phosphorylation and sumoylation. We believe that NR5A receptors represent an ideal model system for investigating how sumoylation alters gene expression. Using both biochemical and mouse genetics we are finding that sumoylation represents an important modification for directing cell specification during development. Our recent work by Campbell et al. 2008 suggests that some target genes will be sumo-sensitive while others will be much less sensitive. This hypothesis is being tested in an in vivo mouse model system

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Mechanisms of Hormone Action in Organ Development and Disease



RF18 | PSAT143 Brain Determinants of Dynamic Bone Remodeling in Females.

Journal of the Endocrine Society

Muriel Babey, William Krause, Xiao Zhang, Jennay Argiris, Joni Nikkanen, Candice Herber, Erica Scheller, Holly Ingraham

An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice.

Science (New York, N.Y.)

Nikkanen J, Leong YA, Krause WC, Dermadi D, Maschek JA, Van Ry T, Cox JE, Weiss EJ, Gokcumen O, Chawla A, Ingraham HA

Running the Female Power Grid Across Lifespan Through Brain Estrogen Signaling.

Annual review of physiology

Ingraham HA, Herber CB, Krause WC

Oestrogen engages brain MC4R signalling to drive physical activity in female mice.


Krause WC, Rodriguez R, Gegenhuber B, Matharu N, Rodriguez AN, Padilla-Roger AM, Toma K, Herber CB, Correa SM, Duan X, Ahituv N, Tollkuhn J, Ingraham HA

Chronic Stimulation of Arcuate Kiss1 Neurons Decreases Bone Mass in Female Mice.

Journal of the Endocrine Society

Ruben Rodriguez, Candice B Herber, William C Krause, Holly A Ingraham