Henry J. Pownall, Ph.D.
Chief and Professor
Co-director, Atherosclerosis and Vascular Biology Research Training Program
Basic and Clinical Research
My research focuses on several aspects of the "Metabolic Axis of Evil," that links obesity, type 2 diabetes, dyslipidemias, and atherosclerosis. Given that obesity, diabetes and lipid disorders involve a dysregulation of energy transport, our research has focused on mechanisms that control fatty acid transport and storage in cellular models of adipose tissue and skeletal muscle. We have developed a testable physiological model for the redistribution of fatty acids from specific fat depots to other sites of metabolism including central fat, the liver, skeletal muscle and heart.
Studies in this area include those that would identify the rate-limiting step in adipogenesis and determine whether adipogenic enzymes are located on a protein scaffold in fat cells. Other studies would determine the mechanism by which glycerol-3-phosphate acyltransferase and 1-acylglycerol-3-phosphate acyltransferase catalyze the acylation of glycerol precursors of triglyceride synthesis. A related topic is the mechanism by which very low-density lipoprotein, or VLDL precursors are fully lipidated as secretion-competent VLDL. The final component of the "Metabolic Axis of Evil" is atherosclerosis.
Our studies of atherogenesis focus on the mechanism(s) by which plasma high-density lipoproteins, or HDL are remodeled and recognized by the hepatic scavenger receptor Class B, Type 1 (SR-B1). Our goal is to use physicochemical principles to identify the mechanism by which cholesteryl esters and triglyceride are selectively removed from HDL by SR-BI. Moreover, it is our goal to use fluorescence-based methods to determine the fate of the cholesteryl esters and triglycerides following their endocytosis. These studies will combine conventional spectrofluorimetry with fluorescence microscopy in our new state-of-the-art facilities. We also collaborate with other investigators in several closely related areas. One of these is a cryoelectron microscopic study of cholesteryl ester- and triglyceride-rich lipoproteins from normal subjects and diabetic, hypertriglyceridemic patients. Another is a study of the impact of hyperhomocysteinemia on atherogenic and dyslipidemic mechanisms. These studies in biophysics, biochemistry, and cell biology are conducted in a mixed clinical/basic research setting that focuses on lipid disorders and vascular disease.
Contact
Phone: 713-798-4160
Fax: 713-798-9005
E-mail: hpownall@bcm.edu
Selected Publications:
- Pownall HJ, Ehnholm C. The unique role of apolipoprotein A-I in HDL remodeling and metabolism. Curr Opin Lipidol 2006;17:209-13.
- Qu SJ, Fan HZ, Gillard BK, Pownall HJ. N-Glycosylation is required for secretion-competent human plasma phospholipid transfer protein. Protein J 2006;25:167-73.
- Lloyd EE, Gaubatz JW, Burns AR, Pownall HJ. Sustained elevations in NEFA induce cyclooxygenase-2 activity and potentiate THP-1 macrophage foam cell formation. Atherosclerosis 2007;192:49-55.
- Liao D, Tan H, Hui R, Li Z, Jiang X, Gaubatz J, Yang F, Durante W, Chan L, Schafer AI, Pownall HJ, Yang X, Wang H. Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance. Circ Res 2006;99:598-606.
- Massey JB, Pownall HJ. Structures of biologically active oxysterols determine their differential effects on phospholipid membranes. Biochemistry 2006;45:10747-58.
- Pownall HJ. Detergent-mediated phospholipidation of plasma lipoproteins increases HDL cholesterophilicity and cholesterol efflux via SR-BI. Biochemistry 2006;45:11514-22.
- Gaubatz JW, Gillard BK, Massey JB, Hoogeveen RC, Huang M, Lloyd EE, Raya JL, Yang CY, Pownall HJ. Dynamics of dense electronegative low density lipoproteins and their preferential association with lipoprotein phospholipase A(2). J Lipid Res 2007;48:348-57.
- Pownall HJ, Hosken BD, Gillard BK, Higgins CL, Lin HY, Massey JB. Speciation of Human Plasma High-Density Lipoprotein (HDL): HDL Stability and Apolipoprotein A-I Partitioning. Biochemistry 2007;46:7449-59.
- Volcik K, Ballantyne CM, Pownall HJ, Sharrett AR, Boerwinkle E. Interaction effects of high-density lipoprotein metabolism gene variation and alcohol consumption on coronary heart disease risk: the atherosclerosis risk in communities study. J Stud Alcohol Drugs 2007;68:485-92.
- Baiba K. Gillard, Harry S. Courtney, John B. Massey and Henry J. Pownall. Serum Opacity Factor Reveals Human Plasma High Density Lipoprotein Instability via Selective Delipidation and Apolipoprotein Desorption 2007 Biochemistry, Submitted.