Our Research

Photo Credit: Dr. James Bayrer

 

Understanding Intestinal Epithelial Biology

The intestinal epithelium comprises the human body’s greatest environmentally exposed surface and represents the largest sensory and endocrine organ. We utilize intestinal organoids and animal models to understand how the intestine senses and responds to regular and inflammatory stimuli. By investigating the molecular pathways involved, we aim to discover new ways to promote intestinal wound healing and modulate the signals contributing to visceral pain syndromes.

 


Photo Credit: Dr. William Krause

 

Sex-Dependent Central Regulation of Female Metabolism and Physiology

We are broadly interested in how the female brain uniquely controls a wide-range of sex-specific physiological responses. Currently, we focus on estrogen signaling in the medial basal hypothalamus (MBH) that includes the ventromedial hypothalamus (VMH) and the arcuate nucleus (ARC). Mouse models coupled with genomics and pharmacogenetics are leveraged to define the estrogen-sensitive neuronal modules important in locomotion, thermogenesis, reproduction and bone density. Our research program is highly relevant to age-related diseases in hormone deficient stages and to women’s health. 

 

 

Photo Credit: Dr. Diego Miranda

 

Linking Lipid Ligands With Nuclear Receptor Function

Ongoing research focuses on NR5A nuclear receptors, SF-1 and LRH-1 because of their critical roles in various aspects of metabolism. We are currently working to understand a puzzling question posed by our earlier structural studies – why would phospholipids serve as NR5A ligands. This is being explored for LRH-1 in two model systems, the liver hepatocyte, and the mouse or human intestinal organoid. Efforts are underway to find synthetic ligands that could prove useful in fatty liver disease and inflammatory bowel disease.

 
 
 
 
 
 
 

Recent Publications

Xing Y, Morohashi KI, Ingraham HA, Hammer GD. Development. 2017 Sep 11. 
Bellono NW, Bayrer JR, Leitch DB, Castro J, Zhang C, O'Donnell TA, Brierly SM, Ingraham HA, Julius DJ. Cell. June 2017
Correa SM, Newstrom DW, Warne JP, Flandin P, Cheung CC, Lin-Moore AT, Pierce AA, Xu AW, Rubenstein JL, Ingraham HA. Cell Rep. 2015 Jan 6;10(1):62-74.