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Daniel S. Ory, MD

Professor of Medicine, Cell Biology and Physiology

Phone314-362-8737

Fax314-362-0186

Emaildory@wustl.edu

Additional Titles

  • Co-Director, BioMed21 Diabetic Cardiovascular Disease Center
  • Director of Admissions, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO
  • Director, Washington University Metabolomics Facility
  • Co-Director, Diabetic Center for Cardiovascular Disease
  • Alan A. and Edith L. Wolff, Distinguished Professor of Medicine

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Education

  • Intern and Residency, Medicine: Brigham & Women's Hospital, Harvard Medical School, Boston, MA (1989)
  • Clinical Fellow, Medicine: Harvard Medical School, Boston, MA (1989)
  • Fellow, Cardiac Unit: Massachusetts General Hospital, Harvard Medical School, Boston, MA (1992)
  • Research Fellow, Medicine: Harvard Medical School, Boston, MA (1992)
  • Visiting Scientist: Whitehead Institute for Biomedical Research, Cambridge, MA (1995)

Board Certifications

  • Cardiovascular Disease

Recognition

1980

John Harvard Scholarship

1982

Magna Cum Laude, Harvard College, Cambridge, MA

1986

Cum Laude, Harvard Medical School, Boston, MA

2002

Member, Scientific Advisory Board, National Niemann-Pick Disease Foundation

2003

Editorial Board Member, Journal of Biological Chemistry

2004

Elected, American Society for Clinical Investigation (ASCI)

2007

Chairman, Scientific Advisory Board, National Niemann-Pick Disease Foundation

2008

Elected, Fellow of American Association of Advancement of Science (AAAS)

2012

Elected, American Association of Physicians (AAP)

2013

Guardian Angel Award, Dana’s Angels Research Trust

2014

Perseverance Award, National Niemann-Pick Disease Foundation

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

View publications on PubMed.gov