The goals of our research are to understand the development of proatherogenic metabolic abnormalities in insulin resistant individuals, and to identify new therapeutic targets for improving these abnormalities. Two current areas of focus are dysregulation of (i) lipoprotein and (ii) bile acid metabolism. Lipoproteins carry out atherogenic and atheroprotective actions, and may link insulin resistance with cardiovascular disease. Bile acids are involved in maintaining cholesterol, glucose, and triglyceride homeostasis, and are dysregulated during insulin resistance and diabetes. Through these two research areas, we aim to determine mechanisms of metabolic abnormalities and atherogenesis in the natural history of type 2 diabetes, and to identify potential therapeutic targets.
FoxO Transcription Factors are Required for Hepatic HDL-Cholesterol Clearance
Lee SX, Heine M, Schlein C, Ramakrishnan R, Liu J, Belnavis G, Haimi I, Fischer AW, Ginsberg HN, Heeren J, Rinninger F, and Haeusler RA.
The Journal of Clinical Investigation doi: 10.1172/JCI94230. [Epub ahead of print]
Biochemical and cellular properties of insulin receptor signaling
Haeusler RA, McGraw TE, Accili D.
Nature Reviews Molecular Cell Biology 19: 31-44
Selective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic Glucose Handling
Langlet, Haeusler RA, Linden D, Ericson E, Norris T, Johansson A, Cook JR, Aizawa K, Sang L, Buettner C, Accili D.
Cell 171: 824-835
Cyp8b1 ablation prevents western diet-induced weight gain and hepatic steatosis because of impaired fat absorption
Bertaggia E, Jensen KK, Castro-Perez J, Xu Y, Di Paolo G, Chan RB, Wang L, Haeusler RA.
American Journal of Physiology – Endocrinology & Metabolism 313: E121-E133
Increased Bile Acid Synthesis and Impaired Bile Acid Transport in Human Obesity
Haeusler RA, Camastra S, Nannipieri M, Astiarraga G, Castro-Perez J, Xie D, Wang L, Chakravarthy M, Ferrannini E.
Journal of Clinical Endocrinology & Metabolism 101: 1935-1944
Increased Bile Acid Synthesis and Deconjugation after Biliopancreatic Diversion
Ferrannini E, Camastra S, Astiarraga G, Nannipieri M, Castro-Perez J, Xie D, Wang L, Chakravarthy M, Haeusler RA.
Diabetes 64: 3377-3385
Temporal changes in bile acid levels and 12-hydroxylation after Roux-en-Y gastric bypass surgery in type 2 diabetes
Dutia R, Embrey M, O’Brien C, Haeusler RA, Agenor K, Homel P, McGinty J, Vincent R, Alaghband-Zadeh J, Staels B, Le Roux C, Yu J, and Laferrere B.
International Journal of Obesity 39: 806-813
Decreased Expression of Hepatic Glucokinase in Type 2 Diabetes
Haeusler RA, Camastra S, Astiarraga B, Nannipieri M, Anselmino N, and Ferranini E.
Molecular Metabolism 4: 222-226
Integrated control of hepatic lipogenesis versus glucose production requires FoxO transcription factors
Haeusler RA, Hartil K, Vaitheesvaran B, Arrieta-Cruz I, Knight CM, Cook JR, Kammoun HL, Febbraio MA, Gutierrez-Juarez R, Kurland IJ, and Accili D.
Nature Communications 5: 5190
Human Insulin Resistance is Associated with Increased Plasma Levels of 12-Hydroxylated Bile Acids
Haeusler RA, Astiarraga B, Camastra S, Accili D, and Ferrannini E.
Diabetes 62: 4184-91
Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing
Pratt-Hyatt M, Pai DA, Haeusler RA, Wozniak GG, Good PD, Miller EL, McLeod IX, Yates JR 3rd, Hopper AK, and Engelke DR.
PNAS 110: E3081-9
Impaired Generation of 12-Hydroxylated Bile Acids Links Hepatic Insulin Signaling with Dyslipidemia
Haeusler RA, Pratt-Hyatt M, Welch CL, Klaassen CD, and Accili D.
Cell Metabolism 15: 65-74
Regulation of hepatic LDL receptors by mTORC1 and PCSK9
Ai D, Chen C, Han S, Ganda A, Murphy AJ, Haeusler R, Thorp E, Accili D, Horton JD, and Tall AR.
Journal of Clinical Investigation 122: 1262-1270
Dissociation of the Glucose and Lipid Regulatory Functions of FoxO1 by Targeted Knockin of Acetylation-Defective Alleles in Mice
Banks AS, Kim-Muller JY, Mastracci TL, Kofler NM, Qiang L, Haeusler RA, Jurczak MJ, Laznik D, Heinrich G, Samuel VT, Shulman GI, Papaioannou VE, and Accili D.
Cell Metabolism 14: 587-597
FoxOs function synergistically to promote glucose production
Haeusler RA, Kaestner KH, and Accili D.
Journal of Biological Chemistry 285: 35245-35248
Hepatic FoxO1 ablation exacerbates lipid abnormalities during hyperglycemia
Haeusler RA, Han S, and Accili D.
Journal of Biological Chemistry 285: 26861-26868