Over the past generation, the costs associated with Diabetes and Obesity to American economy has risen to over $100 billion annually through effects on health care and worker productivity. Research advances that reverse this trend will have a major overall positive effect on the long-term wellness of our Nation as a whole.
Dr. Osborne’s research examines how the body senses differences in the molecular composition of the diet.
Dr. Osborne received his Ph.D. in Microbiology/Molecular Biology from the University of California, Los Angeles.
Activation of the farnesoid X receptor provides protection against acetaminophen-induced hepatic toxicity.
Lee FY, de Aguiar Vallim TQ, Chong HK, Zhang Y, Liu Y, Jones SA, Osborne TF, Edwards PA
Mol Endocrinol. 2010 Aug;24(8):1626-36
Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1.
Chong HK, Infante AM, Seo YK, Jeon TI, Zhang Y, Edwards PA, Xie X, Osborne TF
Nucleic Acids Res. 2010 Oct;38(18):6007-17
A feed-forward loop amplifies nutritional regulation of PNPLA3.
Huang Y, He S, Li JZ, Seo YK, Osborne TF, Cohen JC, Hobbs HH
Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7892-7
Sterol regulatory element binding protein 1a regulates hepatic fatty acid partitioning by activating acetyl coenzyme A carboxylase 2.
Im SS, Hammond LE, Yousef L, Nugas-Selby C, Shin DJ, Seo YK, Fong LG, Young SG, Osborne TF
Mol Cell Biol. 2009 Sep;29(17):4864-72
FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action.
Shin DJ, Osborne TF
J Biol Chem. 2009 Apr 24;284(17):11110-20
SREBP-2 regulates gut peptide secretion through intestinal bitter taste receptor signaling in mice.
Jeon TI, Zhu B, Larson JL, Osborne TF
J Clin Invest. 2008 Nov;118(11):3693-700
Selective binding of sterol regulatory element-binding protein isoforms and co-regulatory proteins to promoters for lipid metabolic genes in liver.
Bennett MK, Seo YK, Datta S, Shin DJ, Osborne TF
J Biol Chem. 2008 Jun 6;283(23):15628-37
A key role for orphan nuclear receptor liver receptor homologue-1 in activation of fatty acid synthase promoter by liver X receptor.
Matsukuma KE, Wang L, Bennett MK, Osborne TF
J Biol Chem. 2007 Jul 13;282(28):20164-71
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Partitioning Circadian Transcription by SIRT6 Leads to Segregated Control of Cellular Metabolism.
Masri S, Rigor P, Cervantes M, Ceglia N, Sebastian C, Xiao C, Roqueta-Rivera M, Deng C, Osborne TF, Mostoslavsky R, Baldi P, Sassone-Corsi P
Cell. 2014 Jul 31;158(3):659-672
Timothy Osborne's Research Focus
Cardiovascular Diseases, Atherosclerosis, Metabolic Syndrome, Obesity, Type 2 Diabetes, Aging-Related Diseases, Cancer, Heart Disease, Infectious Diseases, Pathogen Invasion, Inflammatory Bowel Disease, Inherited Disorders, Metabolic Diseases, Diabetes - General, Monogenic Diabetes, Type 1 Diabetes
Watch Dr. Osborne describe his research
The Osborne laboratory's study into the regulation of cholesterol and fatty acid metabolism and their interconnectedness has been expanded to determine how lipid metabolism is integrated into more global aspects of physiology and cell biology. A major focus of their work has been on the sterol regulatory element binding proteins (SREBPs) and over the last 15 years the lab has made and validated several molecular reagents and assay systems for studying SREBPs using in vitro, cell culture based and whole animal model systems. More recent studies combine animal knockout and genome-wide approaches that indicate SREBPs are at the intersection of nutrient sensing and many other cell-environment interactions including responses to organic and biological threats.
Timothy Osborne's Research Report
The focus of our research is on how fundamental processes of gene regulation are used in the control and management of metabolic homeostasis. Our primary studies are in mammalian lipid metabolism and the two main lipids in mammalian cells are fatty acids and sterols. In one major area, we study how dietary and metabolic fluctuations alter flux of acetyl CoA into either cholesterol or fatty acids. A major decision point for this is at the gene expression level where changes in mRNA levels result in changes in the concentration of key enzymes in the two pathways to alter acetyl CoA flux accordingly. We are using molecular genetic and biochemical techniques to evaluate how the sterol regulatory element binding proteins (SREBPs) sense the need to shift the flux in response to changing metabolic conditions.
About Timothy Osborne
Timothy Osborne, Ph.D., received his doctorate in Microbiology/Molecular Biology from the University of California, Los Angeles (UCLA), and conducted postdoctoral research in the lab of Nobel Prize winners, Brown and Goldstein at the University of Texas at Southwestern Medical School. Dr. Osborne was most recently chair of the Department of Molecular Biology and Biochemistry at UC Irvine. He received UCI’s Chancellor’s Award for Excellence in Mentoring Undergraduate Research, was elected to Who’s Who in American University Professors, was recognized as an Established Investigator of the American Heart Association and is a recipient of a Lucille P. Markey Scholar Award in Biomedical Science.
Ph.D., University of California Los Angeles
A.B., University of California Santa Barbara