Willa Hsueh, M.D.
Education and Training
B.S. Ohio State University, Columbus, OH (Pre-med)
General Medicine Internship, Johns Hopkins Hospital, Baltimore, MD
Dr. Hsueh joined the faculty at the Los Angeles County/University of Southern California (LAC/USC) Medical Center as an Assistant Professor of Medicine in 1979. While there, she received a Clinical Investigator Award from the National Institute of Arthritis, Metabolism, and Digestive Diseases (NIAMDD). Dr. Hsueh received a Career Development Award from the NIAMDD in 1982, and was promoted to Associate Professor of Medicine at LAC/USC the following year. She continued to earn peer-reviewed funding from the National Institutes of Health and the American Heart Association for her research, including a MERIT award. In 1988, Dr. Hsueh became a full Professor of Medicine and Chief of the Diabetes, Hypertension, and Nutrition Division at LAC/USC. She would eventually become the Chief of the Division of Endocrinology, Diabetes, and Hypertension at the LAC/USC School of Medicine in 1993, a position she held until assuming the same position at the David Geffen School of Medicine at the University of California at Los Angeles (UCLA) in 1997. While at UCLA, Dr. Hsueh was Principal Investigator on several NIH grants, including a DERC, and published several papers in peer-reviewed medical journals. In 2007, Dr. Hsueh joined the Methodist Hospital Research Institute as Director of the Diabetes Research Center and Head Section, of the Division of Diabetes, Obesity & Lipids Department of Medicine.
Dr. Hsueh and her team have led the field in diabetes and cardiovascular research. They were the first to identify a protective role for ligands of the nuclear receptor peroxisome proliferator activated receptor (PPAR) in vascular injury and diabetes complications, particularly in regulation of genes that may mediate vascular complications. They demonstrated that nuclear receptors are expressed on multiple cells of the vasculature, heart, and kidney, and that activation not only has anti-inflammatory effects, but anti-fibrotic and anti-oxidant activities as well. In translational investigations, Dr. Hsueh and her colleagues demonstrated that coronary vascular damage occurs during insulin resistance in the absence of traditional cardiovascular disease risk and may be related to adipokine production and inflammatory changes, all of which are improved by PPAR? agonists. Indeed, the PPAR? class of therapeutics has emerged as an important strategy in the war against metabolic syndrome and diabetes. In addition, her team has collaborated with genetics colleagues identified multiple genetic polymorphisms associated with both insulin resistance and cardiovascular disease in Mexican Americans. More recently, they have also been interested in adipogenesis as it relates to development of obesity and nonalcoholic steatohepatitis. Dr. Hsueh is an author of over 135 peer reviewed publications, mostly concerned with observations in these areas of research.
Dr. Hsueh's research interests focus on insulin resistance and mechanisms of cardiovascular disease, nuclear receptors, the renin-angiotensin system, and vascular/renal complications of diabetes mellitus. The goal of her research program is to translate observations from her research laboratory to human pathophysiology and prevention of disease. More specifically, she is building a multidisciplinary team to investigate novel mechanisms of inflammation as they impact obesity and cardiovascular disease in order to identify new therapeutic targets. Her team will expand their expertise to include nuclear receptors beyond PPARs and to work closely with John Baxter, Paul Webb, and their team to elucidate the structure/function relationships of nuclear receptor ligands and identify new treatments. This expanded goal includes Genomics and microRNA relationships to nuclear receptors, bioinformatics, state-of-the-art imaging with the ability to follow trafficking of inflammatory cells into tissue in vivo, combined with cutting-edge metabolic assessment in mice, high throughput screening, and translational studies. This integrated approach will be critical for identifying new treatment and prevention targets for metabolic syndrome and diabetes. Current specific areas include nuclear receptor relationships to novel antioxidant pathways, mitochondrial function in fatty heart and fatty liver, adipogenesis and response to high fat diet, and monocyte biomarkers of metabolic syndrome.
Diabetes Mellitus, vascular complications, nuclear receptors, adipogenesis
Huang D, Zhou X, Lyon CJ, Hsueh WA, Wong S. MicroRNA-integrated and Network-embedded Gene Selection with Diffusion Distance. Plos One. In press, 2010.
Gupte AA, Liu JZ, Ren Y, Minze LJ, Wiles JR, Collins AR, Lyon CJ, Pratico D, Finegold M, Webb P, Baxter JD, Moore D, Hsueh WA. Rosiglitazone attenuates liver injury in a novel mouse model of steatohepatitis. Hepatology. In Press, 2010.
Hsueh WA, Davidai G, Henry R, and Muduliar, S. Telmisartan effects on insulin resistance in obese or overweight adults without diabetes or hypertension. J Clin Hypertens. [Epub ahead of print] July 2010.
Hsueh WA, Orloski L, and Wyne K. Prediabetes: The importance of early identification and intervention. Postgraduate Medicine. 122(4); 1-15, 2010.
Liu JZ, Lyon CJ, Hsueh WA, and Law RE. A dominant-negative PPAR? mutant promotes cell cycle progression and cell growth in vascular smooth muscle cells. PPAR Research. 2009:438673, 2010.
Collins AR, Lyon CJ, Xia X, Liu JZ, Tangirala RK, Yin F, Boyadjian R, Bikineyeva A, Praticò D, Harrison DG, Hsueh WA. Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes. Circ Res. Mar 27;104(6):e42-54., 2009.
Nicholas S, Liu J, Kim J, Ren Y, Collins A, Nguyen L, Hsueh WA. Critical Role of Osteopontin in the Diabetic Kidney. Kidney International. Dec 31: 1-16, 2010.Takata Y, Liu J, Yin F, Collins A, Barish G, Evans R, Hsueh WA, Tangirala R. Nuclear Hormone Receptor PPAR? Activation Inhibits Accelerated Atherosclerosis by Novel Anti-inflammatory Mechanisms. PNAS. 105(11):4277-4282, 2008.
Caglayan E, Stauber B, Collins A, Lyon C, Yin F, Liu J, Rosenkranz S, Erdmann E, Peterson L, Ross R, Tangirala R, Hsueh WA, Differential Roles of Cardiomyocyte and Macrophage PPARg in Cardiac Fibrosis. Diabetes. 57(9):2470-9, 2008.
Bradley M, Tangirala R, Lusis A, Hsueh WA, Collins J, Tontonoz P. Ligand activation of LXRbeta reverses atherosclerosis and cellular cholesterol overload in LXRalpha-/- ApoE-/-mice. J Clin Invest. 117(8):2337-46, 2007.
Hsueh WA, Abel ED, Breslow J, Maeda N, Davis RC, Fisher EA, Dansky H, McClain DA, Mclndoe R, Wassef MK, Rabadan-Diehl C and Goldberg IJ. Recipes for creating animal models of diabetic cardiovascular disease. Cir Res. 100:1415-1427, 2007.