Atherosclerosis and Lipoprotein Research Lab

Pownall lab

Henry J. Pownall, PhD

Professor of Bioenergetics

Houston Methodist

Weill Cornell Medical College

The Laboratory of Atherosclerosis and Lipoprotein Research seeks to identify the mechanisms underlying atherogenesis and how to prevent it. Foremost among these mechanisms is reverse cholesterol transport (RCT), i.e., transfer of cholesterol from the arterial wall and other peripheral tissues to the liver for disposal. The major RCT mediator is high density lipoproteins (HDL); thus the lab’s focus is HDL biogenesis, the mechanisms by which distinct HDL subspecies are formed, and the role of specific amino acids within the major HDL proteins, apolipoprotein AI, in HDL formation. Lab staff also discovered an alternative RCT pathway and plan to further validate this pathway and determine whether it is impaired in patients with atherosclerosis.  Testing a newly-identified cholesterol-lowering bacterial protein will aid in the design of new anti-atherogenic therapies that enhance RCT.  On the clinical side, the lab participates in a large trial (LookAhead) of the effects of weight loss among obese, diabetic patients.

 

Our Team:

Henry J. Pownall, PhD – Scientist, Principal Investigator

Dr. Pownall’s doctoral training was in physical chemistry with postdoctoral fellowships in molecular spectroscopy at the University of Houston, and biochemistry at Baylor College of Medicine with an emphasis on lipid metabolism. Over time he moved his studies from molecules to in vivo models, studying biophysics, peptide design, lipid synthesis and enzymology, and cell and molecular biology. His work is centered on high density lipoprotein therapeutics, and energy metabolism as it relates to obesity-linked diabetes and human lipid metabolism. A major goal of his research is to determine how alcohol ingestion contributes to enhanced postprandial lipemia, attendant pancreatitis, or alcohol-induced reduction of cardiovascular disease, an effect mediated by increased HDL-cholesterol.

His research is multidisciplinary, with extensive collaboration with structural biologists, endocrinologists, and x-ray crystallographers. Structural biologists provide expertise in lipid and lipoprotein structure by electron cryo microscopy. Endocrinologists have synergistic interests in the lipid disorders found in HIV-positive patients on highly active anti retroviral therapies. X-ray crystallographers help discern the total structure of Streptococcal serum opacity factor (SOF) for determination of structure function relationships.

 

Dr. Pownall maintains an active academic program. He is a member of three graduate programs at Baylor College of Medicine (Structural Computational Biology and Molecular Biophysics, Cell and Molecular Biology, and Cardiovascular Sciences) in which he teaches classes and serves on graduate advisory and qualifying exams committees. He is also active in community education, giving lectures on molecular ethics to local groups including several churches, home owner associations and garden clubs.

Baiba Gillard, PhD – Research Scientist

Baiba Gillard, PhD, received a doctorate in physical organic chemistry from Washington University in St. Louis, Missouri.  She conducted postdoctoral training in biochemistry at Baylor College of Medicine and in biomedical research at UCLA. Gillard joined the faculty of the Department of Medicine at Baylor College of Medicine to work with Donald Marcus, MD, in glycobiology.  Since 2002, she has worked with Henry Pownall, PhD, gaining research expertise in lipid and lipoprotein metabolism and atherosclerosis. In the Pownall laboratory, Gillard is in charge of cell biology of numerous athero-, diabetes-, and lipid-relevant cell lines, and lipid analysis. She is currently a research scientist at HMRI, and a faculty member of Weill Cornell Medical College.  

 

Biwei Qi – Graduate Research Fellow

Biwei Qi, a visiting medical scholar from Xiangya Hospital, Central South University (CN). She is studying the activity of serum opacity factor (SOF), which is produced by S. pyogenes. SOF activity induces the clouding, i.e, opacification, of human plasma by disrupting the structure of its sole target, high density lipoproteins (HDL).  Currently, it is known that SOF converts HDL to a small remnant, a larger cholesteryl ester-rich micro-emulsion, and lipid-free APOA1.  During this reaction, the major HDL proteins, APOE, APOA1, and APOA2 are differentially transferred to the reaction products.  To extend our understanding of the SOF reaction, she has used size exclusion chromatography and, in collaboration with the United States Center for Disease Control and Prevention, asymmetric flow flow-field fractionation (AF4).  Using these methods, she showed that SOF redistributes many other HDL proteins as well as plasma enzymes and lipid-transfer proteins.  She plans to present her findings at the 2020 American Heart Association Meeting, “Vascular Discovery: From Genes to Medicine” (Chicago). 

Jing Liu – Graduate Research Fellow

Jing is a visiting medical scholar from Xiangya Hospital, Central South University, she is studying cholesterol metabolism in the context of multiple pathological states—atherosclerosis, obesity-lined diabetes, sepsis, and infertility. Her in vitro studies of high density lipoprotein (HDL)-free cholesterol bioavailability are complemented by in vivo metabolic studies in HDL receptor-deficient mice.  To advance these studies she has used chemical kinetics, radio-isotope methodology, lipid/lipoprotein isolation methods, lipid analysis, and studies in living cells. In 2019, she has reported her findings at the annual meeting of the Methodist Association for Postdoctoral and Trainee Affairs and at the George and Angelina Kostas Research Center for Cardiovascular Nanomedicine Annual International Meeting.  

Publications:

 

  1. Gillard, BK, PJ Rodriguez, DW Fields, JL Raya, WR Lagor, C Rosales, HS Courtney, AM Gotto Jr and HJ Pownall.  Streptococcal Serum Opacity Factor promotes Cholesterol Ester Metabolism and Bile Acid Secretion In Vitro and In Vivo.  Biochim Biophys Acta 1861:196-204, 2016.  PMID: 26709142
  2. Gillard, BK, GR Bassett, AM Gotto, Jr, C Rosales and HJ Pownall HJ.  Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester.  J Biol Chem 292:8864-8873, 2017.  PMID: 28373285.    
  3. Xu B, BK Gillard, AM Gotto, Jr., C Rosales and HJ Pownall. ABCA1-Derived Nascent High Density Lipoprotein-Apolipoprotein AI and Lipids Metabolically Segregate.  Arterioscler Thromb Vasc Biol 37:2260-2270, 2017. PMID: 29074589.
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