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Structural and Computational Biology and Molecular Biophysics

Houston, Texas

A BCM research lab.
Structural and Computational Biology & Molecular Biophysics
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Henry J. Pownall, Ph.D.

Henry J. Pownall, Ph.D.Chief and Professor, Medicine-Atherosclerosis and Vascular Medicine

Co-Director, Atherosclerosis and Vascular Biology Research Training Program

The Methodist Hospital Research Institute

Education:

B.S., Chemistry, Elizabethtown College (1965)
M.S., Chemistry, Wilkes College (1967)
Ph.D., Chemistry, Northeastern University (1970)
Postdoc, University of Houston and Baylor College of Medicine

Research Interests:

Dr. Pownall physical chemist who has transitioned to cell biology and mouse models of disease without abandoning his commitment to determining molecular mechanisms by physico-chemical methods. Over the decades he has moved his studies from molecules to mice via studies in biophysics, peptide design, lipid synthesis and enzymology, cell biology, and in vivo studies. His studies encompass multiple aspects of lipid metabolism, particularly HDL structure, properties and function in the context of obesity-linked diabetes and atherogenesis. His highlights are as follows: Developed a quantitative model of lipid transfer. Identified structure-function relationships among HDL-remodeling proteins site-directed mutagenesis. Identified the mechanism for phospholipid microsolubilization by apo A-I that is now the widely accepted model HDL formation via the ABCA1 transporter. Determined protein proximity profiles of HDL subfractions by MALDI-MS. Identified determinants of HDL instability by thermodynamic methods. Showed that the HDL-specific activity of Streptococcal serum opacity factor (SOF) enhances multiple that would be expected to remove cholesterol from the arterial wall. Showed that LDL charge is a quantitative function of surface fatty acid density and that LpPLA2 preferentially associates with dense, electronegative LDL. Led study that determined the structure of the LDL-LDLR complex. Many of these studies, which continue to be pursued involve many collaborators.

Dr. Pownall's goals are as follows: To identify other hepatic receptors that lower plasma cholesterol in response to SOF infusion into genetically altered mice; to show that intravenous SOF injection into mice enhances cholesterol disposal from plasma and that this effect is potentiated by co administration of HMG-CoA reductase inhibitors; to show that SOF injection reverses atherosclerosis in mice; to obtain a high resolution X-ray structure of SOF for the design of new structure-function hypotheses.

Selected Publications:

  • Auton M, Basett GR, Gillard BK and Pownall HJ. Free cholesterol determines reassembled high-density lipoprotein phophyolipid phase structure and stability. Biochemistry, 52(25):4324-30 (2013). PubMed
  • Gillard BK, Raya JL, Ruiz-Esponda R, Iyer D, Coraza I, Balasubramanyan A and Pownall HJ. Impaired Lipoprotein Processing in HIV Patients on Antiretroviral Therapy: Aberrant High-Density Lipoprotein Lipids, Stability, and Function. Arterioscler Thromb Vasc Biol, 33(7):1714-21 (2013). PubMed
  • Misra R, Chandra P, Riechman SE, Long DM, Shinde S, Pownall HJ, Coraza I, Lewis DE, Sekhar RV and Balasubramanyam A. Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART). BMC Endocr Disord, 13(1):13 (2013). Pubmed
  • Vu CN, Ruiz-Esponda R, Yang E, Chang E, Gillard B, Pownall HJ, Hoogeveen RC, Coraza I and Balasubramanyam A. Altered replationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: Further evidence for a unique form of Metabolic Syndrome in HIV patients. Metabolism, 62(7):1014-20 (2013). PubMed
  • Bassett GR, Gillard BK and Pownall HJ. Cholesterol determines and limits rHDL formation from human plasma apolipoprotein A-II and phospholipid membranes. Biochemistry, 51(43):8627-35 (2012). PubMed
  • Wang J, Perrard XD, Perrard JL, Mukherjee A, Rosales C, Chen Y, Smith CW, Pownall HJ, Ballantyne CM and Wu H. ApoE and the role of very low density lipoproteins in adipose tissue inflammation. Atherosclerosis, 223(2):342-9 (2012). PubMed
  • Zhang L, Yan F, Zhang S, Lei D, Charles MA, Cavigiolio G, Oda M, Krauss RM, Weisgraber KH, Rye KA, Pownall HJ, Qiu X and Ren G. Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein. Nat Chem Biol, 8(4):342-9 (2012). PubMed

For more publications, see listing on PubMed.

Contact Information:

Department: Medicine
Address: Mail Station F8-049
The Methodist Hospital
6565 Fannin
Houston, TX 77030
Phone: 713-441-7048
E-mail: HJPownall@tmhs.org
Additional Links: Atherosclerosis and Vascular Medicine

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