My lab has focused on defining the molecular mechanisms and transcriptional pathways that contribute toendocrine tissue development and function. Our approaches are broad, spanning structural biology, biochemistry and genetic mouse models. In the last several years we have worked to understand how the class of NR5A orphan nuclear receptors are regulated by both ligands and post-translational modifications, with a new focuson LRH-1 (NR5A2) because of its impact on human health. My lab recently showed thatphosphoinositides are the highest affinity ligands for both SF-1 and LRH-1.
During the last year, we built two new biologically relevant platforms to carry out biochemical and functionalstudies on human LRH-1 (hLRH-1). Our focus on LRH-1 takes advantage of relevant in vivo and ex-vivo systems. The first uses viral infection of mouse liver to acutely knock-out mLRH-1 and add back hLRH-1. The second acutely knock-out/add back strategy is being done in intestinal organoids by my trainee and colleague, Dr. J. Bayrer (Peds GI Physician). Both biological systems are bearing fruit and illustrate why targeting hLRH-1 isworthwhile in both inflammatory bowel and fatty liver diseases.
In addition to maintaining my active lab, I am the Program Director for the UCSF IRACDA Scholars Program, a NIH/NIGMS K12 grant which promotes diversity in the biomedical sciences.
National Advisory Committees:
(1999-Present)Chair, Hormone Action Gordon Conference – 1999, NIH Special Grants Review Committee, NIDDK – 1999, 2001, NIH Endocrinology Study Section – Ad Hoc – Feb 2000, 2001, NIH-NIDDK Program Project Ad-Hoc Review – March 2002, NIH-NIDDK Member Endocrinology Study Section 2002-2005, Ad Hoc Chair, October, 2003. Research Affairs Committee – Endocrinology Society June 2002-Present, Co-organizer of Keystone meeting on Orphan Nuclear Receptors 2004, Chair, Molecular and Cellular Endocrinology NIH Study Section 2004-2006, Chair of Special Review Panel, 2006, Editor of Annual Review of Physiology, Endocrinology Section 2006-2010. Chair SEP NIH Panel, 2008. Co-Chair American Heart Association Review Panel 2008 and 2009. Ad-Hoc Reviewer NIH Special Emphasis Panel Feb 2008, Aug 2008, Feb 2009, March 2009, NIH Challenge Grants, Distinguished Editor for Physiological and Pathological Sciences July 2009, NIH College of CSR Reviewers 2010-2013, NIDDK Stage 2 Editorial Board Review for R24 Collaborative Team Science 2011, NIH/CSR Cell Biology Study Section 2011, Chair - NIH-NIDDK Program Project Ad-Hoc Reviewer 2011, ADA Ad-Hoc Reviewer for Neurohormonal Control of Metabolism, 2012, NIH-NIDDK ZRG-SEP Review, 2012, NIHNIDDK ZEG-SEP and ZDK1-SEP Panels, 2013. American Heart Association Review Panel 2013, 2014, Co-Chair NIH – Directors SEP – Illuminating the Druggable Genome 2014, Ad-Hoc Reviewer NIH IPOD Panel 2014.
Ongoing panels include:
ADA Grant Review Panel 2015-2018,
Annual Review of Physiology Endocrinology Section Editor 2006-Present,
Career Development Review Panel NIDDK-B 2015-2020.
James Bayer, MD/PhD - Assistant Professor
Candice Herber, PhD - Postdoctoral Fellow
William Krause, PhD - Postdoctoral Fellow
Diego Miranda, PhD - Postdoctoral Fellow
Mayra Pastore, PhD - Postdoctoral Fellow
Hazel Escusa, BA - Staff Research Associate
Anne Sufka, BA - IRACDA Scholars Program Coordinator/Lab Operations Manager