Faculty

Daniel S. Ory, MD

ory danielProfessor of Medicine, Cell Biology and Physiology, Cardiovascular Division; Co-Director, BioMed21 Diabetic Cardiovascular Disease Center; Director of Admissions, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO

Contact Information:
BJC Institute of Health Building, Suite 10618
Phone 314-362-8737
Lab 314-362-8794
Fax 314-362-0186

Education and Training:
1986-89 Intern and Resident, Dept. of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA
1986-89 Clinical Fellow, Medicine, Harvard Medical School, Boston, MA
1989-92 Fellow, Cardiac Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA
1989-92 Research Fellow, Dept. of Medicine, Harvard Medical School, Boston, MA
1991-95 Visiting Scientist, Whitehead Institute for Biomedical Research, Cambridge, MA
1992-95 Instructor in Medicine, Harvard Medical School, Boston, MA
1995-96 Instructor in Medicine, Dept. of Internal Medicine, Cardiovascular Division, Washington University School of Medicine
1996-2004 Assistant Professor of Medicine, Dept. of Internal Medicine, Cardiovascular Division, Washington University School of Medicine
2002-06 Asst. Professor of Cell Biology & Physiology, Washington University School of Medicine
2004-08 Associate Professor of Medicine, Cell Biology & Physiology, Washington University School of Medicine
2007-present Co-Director, Diabetic Cardiovascular Disease Center, Washington University School of Medicine
2008-present Professor of Medicine, Cell Biology & Physiology, Washington University School of Medicine
2008-present Faculty Director for Admissions, Division of Biology and Biomedical Sciences, Washington University School of Medicine
2010-present Director, Washington University Metabolomics Facility, Washington University School of Medicine

Honors and Awards:
1980 John Harvard Scholarship
1982 Magna Cum Laude, Harvard College, Cambridge, MA
1986 Cum Laude, Harvard Medical School, Boston, MA
1991 Physician Scientist Award, National Institutes of Health
1991 Postdoctoral Research Fellowship, Howard Hughes Medical Institute
2001 Career Development Award, National Institutes of Health
2002 Member, Scientific Advisory Board, National Niemann-Pick Disease Foundation
2002 Editorial Board Member, Journal of Biological Chemistry
2003 Washington University/Pfizer Biomedical Research Award
2004 Elected, Member of the American Society for Clinical Investigation (ASCI)
2007 Chairman, Scientific Advisory Board, National Niemann-Pick Disease Foundation
2008 Fellow, American Association of Advancement of Science (AAAS)
2010 Editorial Board Member, Journal of Biological Chemistry
2012 Elected, Member of Association of American Physicians (AAP)

Research Interests: 
Cellular cholesterol requirements are met through de novo cholesterol synthesis and uptake of lipoprotein cholesterol. These homeostatic responses are tightly regulated at multiple cholesterol transfer steps and through a negative feedback loop that responds to elevations of membrane cholesterol in the endoplasmic reticulum (ER). Alterations in sterol sensing and trafficking pathways contribute to human inborn errors of metabolism (e.g., Niemann-Pick C disease) and to acquired disease states (e.g., atherosclerosis). The goals of our laboratory are elucidate mechanisms governing these critical cholesterol homeostatic pathways, and to translate our findings to develop biomarkers for prevention and treatment of human disease.

Our work is focused in three broad areas. First, we study molecular mechanisms of regulation of cholesterol homeostasis. In a multidisciplinary approach, we are using biophysical, cell biology and steroid chemistry methods to understand the mechanism through which oxygenated forms of cholesterol ("oxysterols") exert their homeostatic effects. These studies are complemented by an unbiased genetic screen that seeks to identify the molecular machinery responsible for regulation of cellular cholesterol balance. These studies have led to discovery of small RNAs that represent a previously unrecognized mode of regulation for cellular cholesterol homeostasis. The function of candidate molecules identified by this approach are being examined in mouse models of atherosclerosis. Second, we are investigating the function and regulation of the Niemann-Pick C1 (NPC1) protein in cell-based and animal models. These studies involve use of high throughput screens to identify small molecule "chaperones" that correct the protein-folding defect responsible for NPC1 disease. Candidate compounds are being investigated in vivo in a mouse model of NPC1 disease. Third, using mass spectrometry-based lipidomic, we have identified candidate lipid metabolites that are being validated in clinical studies as biomarkers in human disorders associated with oxidative stress, including diabetes and Niemann-Pick C disease.

Publications:  pubmed logo