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Parkson Lee-Gau Chong, PhD

 

Parkson Lee-Gau Chong, PhD

 

Professor, Biochemistry

Telephone:  215-707-4182

Fax:  215-707-7536

Email: pchong02@temple.edu

 

Department of Biochemistry

Center for Substance Abuse Research

 

Educational Background:

 

BS, Tsing-Hua University
MS, Catholic University of America
PhD, University of Illinois at Champaign-Urbana

 

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Research Interests:

 

Project 1: Bipolar Tetraether Liposomes: Lipid Chemistry, Physical Properties, and Technological Applications

 

The long-term goals of this research are to understand how the Archaea live in extreme environments and to use the Archaeal bipolar tetraether lipids for technological applications. The Archaea are curious and remarkable organisms; and, their lipids are structurally distinctly different from their bacterial and eukaryotic counterparts. The native habitat of the thermoacidophilic archaeon Sulfolobus acidocaldarius, which is the focus of this research, is hot (65-80 oC) and acidic (pH 2-3) sulfur springs. The plasma membrane of S. acidocaldarius not only serves as a barrier between the low pH extracellular environment and the neutral pH intracellular compartment (pH 6.5), but also performs proton pumping and other cellular activities at high temperatures. The ability of the plasma membrane to achieve these goals in extreme environments is not clearly understood, although there is evidence suggesting that it has something to do with its unique bipolar tetraether lipid structures which contain cyclopentane rings, branched methyl groups, ether linkages, and sugar moieties. The objective of this research is to elucidate the physical origin of the remarkable thermal, chemical, and mechanical stability of the archaeal plasma membrane via a systematic study on the physical properties of liposomes composed of bipolar tetraether lipids (specifically, polar lipid fraction E, PLFE) isolated from S. acidocaldarius. Fluorescence spectroscopy and microscopy, photon correlation spectroscopy, FT-IR, small angle X-ray scattering, high-pressure probe techniques, pressure perturbation calorimetry, differential scanning calorimetry, electron microscopy, proteomics, and molecular modeling are the major tools used in this research. Temperature, pressure, pH and salt concentrations are the experimental variables. Membrane properties being investigated include solute permeability, molecular packing, vesicle fusion, compressibility, free volume and volume fluctuations, lateral diffusion, and protein-lipid interactions. These studies will give molecular insights into the structure-function relationship of thermoacidophilic archaeal membranes and may also lead to the development of PLFE liposomes or films for applications in coating, storage, membrane protein crystallization, and targeted drug delivery. We are currently developing nano-scale archaeosomes to deliver anti-vascular drugs to solid tumors.

 

Project 2: Sterol Superlattices: physical properties, biological functions, and technological applications

 

.Sterol superlattice is a novel concept for understanding the structural and functional role of cholesterol in membranes. This concept was first proposed from our laboratory in 1994. The current view of sterol superlattice formation is depicted below. The rectangle-like objects represent a lipid membrane, where regular (shaded areas) and irregular (blank areas) regions coexist. In regular regions, sterol molecules are regularly distributed into either hexagonal or centered rectangular superlattices within the host lipid matrix. There is a biphasic change in proportion of irregular region to regular region (R, solid line), membrane free volume (V, solid line), and the perimeter of regular region (P, dashed line) with membrane cholesterol content in the neighborhood of a critical sterol mole fraction Cr (e.g., 20.0, 22.2, 25.0, 33.3, 40.0 and 50.0 mol% sterol in diacylphosphoacylglycerides). The Cr values can be predicted from the sterol superlattice theories. The perimeter of the regular region is proportional to the size of the regular region. Thus the perimeter (P) of the regular regions may increase abruptly at Cr causing a large increase in the interfacial area between the regular and irregular regions, making sterols at Cr more exposed to the aqueous phase than sterols at non-Cr. We have previously shown that the extent of sterol superlattice regulates the activities of surface acting enzymes (e.g., phospholipase A2 and cholesterol oxidase), drug partitioning into membranes, and free radical-induced sterol oxidation. We will continue to elucidate the importance of sterol superlattice in membrane functions and cellular activities. Our current research addresses the following questions: (1) Do sterol superlattices (from model membrane studies) and membrane rafts (from cell biology studies) share the same physical origin? (2) What is the role of sterol superlattice in signal transduction, lipid metabolism, lipid trafficking, and inflammatory responses? (3) How to use the concept of sterol superlattice to develop new technological applications (a US patent (a sensitive method to assess the potency and possible adverse effects of anti-oxidants) is pending). These studies may shed light on the etiological role of cholesterol in cardiovascular disease, Alzheimer’s disease, cancer, diabetes and other disorders.

 

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LABORATORY PERSONNEL:

 

Graduate Students:

  • Varsha Daswani, Biochemistry PhD Program
  • Umme Ayesa, Biochemistry PhD Program

Undergraduate Students:

  • Stephen Morgado
  • Chong Kim
  • Oxana Placinta
  • Stephanie Cheung
  • Chung Tran
  • Jacqueline Rivera
  • Mohd A. Raihan
  • Anuragh Trikha

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other selected Publications:

 

Sugar, I.P. and Chong, P.L.-G. (2012) A Statistical Mechanical Model of Cholesterol/Phospholipid Mixtures: Linking Condensed Complexes, Superlattices and the Phase Diagram. Journal of American Chemical Society, 134, 1164-1171.

 

Chong, P.L.-G., Ayesa, U., Daswani, V., and Hur, E.C. (2012) On Physical Properties of Tetraether Lipid Membranes: Effects of Cyclopentane Rings. Archaea, vol. 2012, Article ID 138439, 11 pages. doi:10.1155/2012/138439.

 

Zhai, Y., Chong, P.L.-G., Taylor, L.J.A., Erlkamp, M., Grobelny, S., Czeslik, C., Watkins, E., and Winter, R. (2012) Physical Properties of Archaeal Tetraether Lipid Membranes as Revealed by Differential Scanning and Pressure Perturbation Calorimetry, Molecular Acoustics, and Neutron Reflectometry: Effects of Pressure and Cell Growth Temperature. Langmuir, 28, 5211-5217.

 

Samson, R.Y., Obita, T., Hodgson, B., Shaw, M., Chong, P.L.-G., Williams, R., and Bell, S.D. (2011) Molecular and Structural Basis of ESCRT-III Recruitment to Membranes during Archaeal Cell Division. Molecular Cell, 41, 186-196.

 

Jeworrek, C., Evers, F., Erlkamp, M., Grobelny, S., Tolan, M., Chong, P.L.-G., and Winter, R. (2011) Structure and Phase Behavior of Archaeal Lipid Monolayers. Langmuir, 27, 13113–13121.

 

Chong, P.L.-G. (2008) Physical Properties of Membranes Composed of Tetraether Archaeal Lipids. In “Thermophiles: Biology and Technology at High Temperatures”, (Robb, F., Antranikian, G., Driessen, A., and Grogan, D., eds.), CRC Press, FL., pp.75-97.

 

Chong, P.L.-G., and Olsher, M. (2004) Fluorescence Studies of Lipid Lateral Organization in Liposomal Membranes (review). Soft Materials, 2, 85-105.

 

Chong, P.L.-G., Zein, M., Khan, T.K., and Winter, R. (2003) Structure and Conformation of Bipolar Tetraether Lipid Membranes Derived from Thermoacidophilic Archaeon Sulfolobus acidocaldarius as Revealed by Small-Angle X-Ray Scattering and High Pressure FT-IR Spectroscopy. J. Phys. Chem. 107, 8694-8700.

 

Gliozzi, A, Relini, A., and Chong, P.L.-G. (2002) Structure and Permeability Properties of Biomimetic Membranes of Bolaform Archaeal Tetraether Lipids (review). J. Membrane Science, 206, 131-147.

 

Wang, M.M., Sugar, I.P., and Chong, P.L.-G. (2002) Effect of Double Bond Position on Dehydroergosterol Fluorescence Intensity Dips in Phosphatidylcholine Bilayers with Saturated sn-1 and monoenoic sn-2 acyl chains. J. Phys. Chem. 106, 6338-6345.

 

Zhou, J.G., Koulas, S., and Chong, P.L.-G. (2000) Shape Memory Alloy Activated High-Pressure Optical Cell for Biophysical Studies. Rev. Sci. Instrum. 71, 4249-4256.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24613478. Shah SP, Jansen SA, Taylor LJ, Chong PL, Correa-Llantén DN, Blamey JM, Lipid composition of thermophilic Geobacillus sp. strain GWE1, isolated from sterilization oven. Chem Phys Lipids 180:(61-71)2014 May

23028246. Chong PL, Ayesa U, Daswani VP, Hur EC, On physical properties of tetraether lipid membranes: effects of cyclopentane rings. Archaea 2012:(138439)2012

22824272. Venegas B, Zhu W, Haloupek NB, Lee J, Zellhart E, Sugár IP, Kiani MF, Chong PL, Cholesterol superlattice modulates CA4P release from liposomes and CA4P cytotoxicity on mammary cancer cells. Biophys J 102:9(2086-94)2012 May 2

21081080. Chong PL, Sulc M, Winter R, Compressibilities and volume fluctuations of archaeal tetraether liposomes. Biophys J 99:10(3319-26)2010 Nov 17

20060818. Chong PL, Archaebacterial bipolar tetraether lipids: Physico-chemical and membrane properties. Chem Phys Lipids 163:3(253-65)2010 Mar

19535683. Scott RC, Rosano JM, Ivanov Z, Wang B, Chong PL, Issekutz AC, Crabbe DL, Kiani MF, Targeting VEGF-encapsulated immunoliposomes to MI heart improves vascularity and cardiac function. FASEB J 23:10(3361-7)2009 Oct

19477316. Brown DA, Venegas B, Cooke PH, English V, Chong PL, Bipolar tetraether archaeosomes exhibit unusual stability against autoclaving as studied by dynamic light scattering and electron microscopy. Chem Phys Lipids 159:2(95-103)2009 Jun

19172383. Pattillo CB, Venegas B, Donelson FJ, Del Valle L, Knight LC, Chong PL, Kiani MF, Radiation-guided targeting of combretastatin encapsulated immunoliposomes to mammary tumors. Pharm Res 26:5(1093-100)2009 May

19010302. Chong PL, Zhu W, Venegas B, On the lateral structure of model membranes containing cholesterol. Biochim Biophys Acta 1788:1(2-11)2009 Jan

18694720. Olsher M, Chong PL, Sterol superlattice affects antioxidant potency and can be used to assess adverse effects of antioxidants. Anal Biochem 382:1(1-8)2008 Nov 1

18689464. Venegas B, Wolfson MR, Cooke PH, Chong PL, High vapor pressure perfluorocarbons cause vesicle fusion and changes in membrane packing. Biophys J 95:10(4737-47)2008 Nov 15

17980352. Huang P, Xu W, Yoon SI, Chen C, Chong PL, Unterwald EM, Liu-Chen LY, Agonist treatment did not affect association of mu opioid receptors with lipid rafts and cholesterol reduction had opposite effects on the receptor-mediated signaling in rat brain and CHO cells. Brain Res 1184:(46-56)2007 Dec 12

17980152. Huang P, Chen C, Xu W, Yoon SI, Unterwald EM, Pintar JE, Wang Y, Chong PL, Liu-Chen LY, Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor. Biochem Biophys Res Commun 365:1(82-8)2008 Jan 4

17951733. Chong PL, Venegas B, Olsher M, Fluorescence detection of signs of sterol superlattice formation in lipid membranes. Methods Mol Biol 400:(159-70)2007

17951732. Chong PL, Olsher M, Fluorometric assay for detection of sterol oxidation in liposomal membranes. Methods Mol Biol 400:(145-58)2007

17441759. Venegas B, Sugár I, Chong PL, Critical factors for detection of biphasic changes in membrane properties at specific sterol mole fractions for maximal superlattice formation. J Phys Chem B 111:19(5180-92)2007 May 17

17141202. Huang P, Xu W, Yoon SI, Chen C, Chong PL, Liu-Chen LY, Cholesterol reduction by methyl-beta-cyclodextrin attenuates the delta opioid receptor-mediated signaling in neuronal cells but enhances it in non-neuronal cells. Biochem Pharmacol 73:4(534-49)2007 Feb 15

16505160. Xu W, Yoon SI, Huang P, Wang Y, Chen C, Chong PL, Liu-Chen LY, Localization of the kappa opioid receptor in lipid rafts. J Pharmacol Exp Ther 317:3(1295-306)2006 Jun

15980181. Chong PL, Ravindra R, Khurana M, English V, Winter R, Pressure perturbation and differential scanning calorimetric studies of bipolar tetraether liposomes derived from the thermoacidophilic archaeon Sulfolobus acidocaldarius. Biophys J 89:3(1841-9)2005 Sep

15803663. Kanichay R, Boni LT, Cooke PH, Khan TK, Chong PL, Calcium-induced aggregation of archaeal bipolar tetraether liposomes derived from the thermoacidophilic archaeon Sulfolobus acidocaldarius. Archaea 1:3(175-83)2003 Oct

15697233. Olsher M, Yoon SI, Chong PL, Role of sterol superlattice in free radical-induced sterol oxidation in lipid membranes. Biochemistry 44:6(2080-7)2005 Feb 15

14979712. Wang MM, Olsher M, Sugár IP, Chong PL, Cholesterol superlattice modulates the activity of cholesterol oxidase in lipid membranes. Biochemistry 43:8(2159-66)2004 Mar 2

12093540. Chong PL, Sugár IP, Fluorescence studies of lipid regular distribution in membranes. Chem Phys Lipids 116:1-2(153-75)2002 Jun

10823467. Gabriel JL, Chong PL, Molecular modeling of archaebacterial bipolar tetraether lipid membranes. Chem Phys Lipids 105:2(193-200)2000 Apr

10692324. Khan TK, Chong PL, Studies of archaebacterial bipolar tetraether liposomes by perylene fluorescence. Biophys J 78:3(1390-9)2000 Mar

10194297. Liu F, Chong PL, Evidence for a regulatory role of cholesterol superlattices in the hydrolytic activity of secretory phospholipase A2 in lipid membranes. Biochemistry 38:13(3867-73)1999 Mar 30

9718302. Wang MM, Sugar IP, Chong PL, Role of the sterol superlattice in the partitioning of the antifungal drug nystatin into lipid membranes. Biochemistry 37:34(11797-805)1998 Aug 25

9425030. Komatsu H, Chong PL, Low permeability of liposomal membranes composed of bipolar tetraether lipids from thermoacidophilic archaebacterium Sulfolobus acidocaldarius. Biochemistry 37:1(107-15)1998 Jan 6

9129827. Liu F, Sugar IP, Chong PL, Cholesterol and ergosterol superlattices in three-component liquid crystalline lipid bilayers as revealed by dehydroergosterol fluorescence. Biophys J 72:5(2243-54)1997 May

24227345. Chong PL, Liu F, Wang MM, Truong K, Sugar IP, Brown RE, Fluorescence evidence for cholesterol regular distribution in phosphatidylcholine and in sphingomyelin lipid bilayers. J Fluoresc 6:4(221-30)1996 Dec

8672502. Haynes MP, Chong PL, Buckley HR, Pieringer RA, Fluorescence studies on the molecular action of amphotericin B on susceptible and resistant fungal cells. Biochemistry 35:24(7983-92)1996 Jun 18

7937839. Chong PL, Evidence for regular distribution of sterols in liquid crystalline phosphatidylcholine bilayers. Proc Natl Acad Sci U S A 91:21(10069-73)1994 Oct 11

8075336. Chong PL, Tang D, Sugar IP, Exploration of physical principles underlying lipid regular distribution: effects of pressure, temperature, and radius of curvature on E/M dips in pyrene-labeled PC/DMPC binary mixtures. Biophys J 66:6(2029-38)1994 Jun

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