Jay Horton, M.D.

Dr. Jay D. Horton obtained his B.S. and M.D. degrees from the University of Iowa in 1984 and 1988, respectively. He completed his internal medicine residency (1988-1991) and gastroenterology fellowship (1991-1994) at UT Southwestern Medical Center. During his gastroenterology fellowship he studied metabolic regulators of bile acid and cholesterol homeostasis in animals. Following the gastroenterology fellowship, he completed a Howard Hughes post doctoral fellowship in the Department of Molecular Genetics at UT Southwestern Medical Center. The studies in this fellowship focused on the transcriptional regulation of cholesterol and fatty acid synthesis.

In clinical digestive diseases, Dr. Horton has an interest in conditions that lead to steatosis and obesity. Currently the laboratory is investigating molecular mediators of steatosis using various mouse models. Investigations from the laboratory have revealed how the primary transcriptional regulators of cholesterol metabolism (sterol regulatory element-binding proteins) are also key regulators of fatty acid synthesis in liver. A major focus of the laboratory is to determine how these transcriptional regulators contribute to the development of steatosis in various disease processes such as diabetes, obesity, and beta-oxidation defects. A second area of investigation centers on determining the function of PCSK9, a protein that is involved in determining plasma LDL cholesterol levels through its ability to post-transcriptionally regulate the expression of the LDL receptor in liver.

Medical School	University of Iowa Hospitals and Clinics (1988)
Internship/Residency	Parkland Health and Hospital System (1991), Internal Medicine
Fellowship	UT Southwestern Medical Center (1994), Gastroenterology
Fellowship	UT Southwestern Medical Center (1997), Molecular Genetics

• Primary Care - General Internal Medicine

• Primary Interests
• Internal Medicine

• Hepatic steatosis
• Lipid metabolism

Featured Publications

Molecular basis for LDL receptor recognition by PCSK9.

Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J Proc. Natl. Acad. Sci. U.S.A. 2008 Feb 105 6 1820-5

Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells.

McNutt MC, Lagace TA, Horton JD J. Biol. Chem. 2007 Jul 282 29 20799-803

Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice.

Lagace TA, Curtis DE, Garuti R, McNutt MC, Park SW, Prather HB, Anderson NN, Ho YK, Hammer RE, Horton JD J. Clin. Invest. 2006 Nov 116 11 2995-3005

Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9.

Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, Hammer RE, Moon YA, Horton JD Proc. Natl. Acad. Sci. U.S.A. 2005 Apr 102 15 5374-9

Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus.

Shimomura I, Bashmakov Y, Horton JD J. Biol. Chem. 1999 Oct 274 42 30028-32

The Scap/SREBP Pathway Is Essential for Developing Diabetic Fatty Liver and Carbohydrate-Induced Hypertriglyceridemia in Animals.

Moon YA, Liang G, Xie X, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Brown MS, Goldstein JL, Horton JD Cell Metab. 2012 Feb 15 2 240-6

Human fatty liver disease: old questions and new insights.

Cohen JC, Horton JD, Hobbs HH Science 2011 Jun 332 6037 1519-23

Crystal structure of Spot 14, a modulator of fatty acid synthesis.

Colbert CL, Kim CW, Moon YA, Henry L, Palnitkar M, McKean WB, Fitzgerald K, Deisenhofer J, Horton JD, Kwon HJ Proc. Natl. Acad. Sci. U.S.A. 2010 Nov 107 44 18820-5

Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans.

Browning JD, Horton JD J. Lipid Res. 2010 Nov 51 11 3359-63

Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis.

Kim CW, Moon YA, Park SW, Cheng D, Kwon HJ, Horton JD Proc. Natl. Acad. Sci. U.S.A. 2010 May 107 21 9626-31

• Association of American Physicians
  (2008)
• American Society for Clinical Investigation
  (2003)
• Established Investigator
  American Heart Foundation (2000)
• PEW Scholar
  PEW Foundation (2000)
• Research Scholar Award
  American Digestive Health Foundation (1999)