James A. Hamilton, Ph.D.
Professor of Physiology and Biophysics
Research Professor of Medicine
Research: Membrane and Structural Biology
Membrane and Structural Biology; Imaging of fat depots and atherosclerotic plaque.
Research in our group is aimed at providing fundamental information relating to heart disease, diabetes, obesity, and diseases related to fatty acid metabolism. An overall goal to is to develop novel approaches to biomedical issues by integrating physical-chemical and physiological/biochemical approaches. In our newer research this is achieved by assembling multi-disciplinary teams to translate basic research into clinical applications. We use physical and instrumental methods (including solution state 13C NMR spectroscopy, solid state and magic angle spinning multinuclear NMR, multidimensional NMR, MR imaging, and fluorescence) that are tailored to the specific questions we are addressing. These techniques are complemented with molecular modeling, molecular biology and other cell biology methods. Two major areas of our research are described below.
A. Transport of fatty acids.
The overall aim of research relating to obesity and diabetes is to describe structural and dynamic aspects of fatty acid binding and transport in plasma, in cell membranes, and in the cytosol with state-of-the-art methods in both structural and cell biology. We study fatty acid binding and transport in the plasma by albumin, their transport across the plasma membrane and their binding to intracellular fatty acid binding proteins (FABP).
Three specific aims of the fatty acid transport project are illustrated. (i) Elucidating molecular details of fatty acid interactions with albumin, primarily by 13C NMR spectroscopy of complexes with 13C-labeled fatty acids and molecular modeling. Recently we extended our studies of binding of fatty acids by NMR to an integrated study with NMR, x-ray crystallography, and molecular biology. Illustrated below are results with this integrative approach that have correlated the major binding sites in the crystal structure with NMR peaks from the fatty acid (carboxyl carbon). It is now possible to determine the effect of drugs on fatty acid binding in a site-specific manner, and to locate binding sites of other natural ligands and new drugs by NMR spectroscopy.
(ii) Determining the solution NMR structure of intracellular fatty acid and lipid binding proteins with and without ligands.
The 3-dimensional structure of porcine ileal lipid binding protein (ILBP) with bound ligand (glycocholate) is illustrated here. This 127 amino acid protein is in the same family as the intracellular fatty acid binding proteins (FABP) but binds a wider range of ligands, including bile acids. Our NMR solution structure reveals the same general structural motif as found by x-ray crystallography for several FABP: 10 β-strands running antiparallel to each other, plus two small a-helices, which form a β-barrel. The steroid moiety penetrates deep into the internal binding cavity and the polar glycine is at the aqueous interface. We have published the complete structure of another FABP, the human intestinal FABP (cover figure for JBNMR) and have also determined the structure of a mutation associated with diabetes.
(iii) Monitoring movement of fatty acids across membranes and desorption from membranes by multiple fluorescence methods and natural fatty acids.
Transport of fatty acids through membranes is a highly active area of current research in cell biology. The figure of a phospholipid bilayer vesicle illustrates some of the methods that are being used and developed in our lab.
One example of these applications of fluorescence is the monitoring of the transmembrane diffuse (flip-flop) of fatty acids. We developed a hypothesis of fatty acid transmembrane transport that predicts a pH change inside vesicles (or cells) after addition of external fatty acids. As illustrated in the figure of “Flip-flop of Oleic Acid”, our results show fatty acids flip-flop rapidly across a phospholipid bilayer without a protein transporter.
The same approach can be applied to live cells to elucidate pathways of entry of fatty acids into cells, as illustrated by the data shown for fat cells with the two probes ADIFAB and the pH dye BCECF. Fatty acid-induced pH changes in cells are being examined by whole cell fluorescence and video imaging fluorescence in single cells under conditions modeling diabetes and obesity.
B. Atherosclerosis: magnetic resonance imaging (MRI) and NMR spectroscopy.
Another major effort is to develop and apply new NMR and MRI methods for the characterization of lipids in intact atherosclerotic plaques and to correlate NMR spectroscopic data with NMR imaging data. The goals include characterizing lipid phases in specific types of plaques, correlating lipid phase and structures to plaque vulnerability to rupture, and providing information for rigorous interpretation of MR images of plaques. We are studying human, rabbit and mouse plaques. In the rabbit studies we have the opportunity to perform trigger the rupture of a plaque and the formation of a thrombus. In vivo MR imaging has monitored this procedure, and as illustrated in the figure above showing MRI of the aorta of a live rabbit MR images detect the newly formed thrombus. This work could translate into the detection of thrombosis in humans and distinction of the thrombus from plaque in a non-invasive way; i.e., MR imaging. Several new publications from our group have reported our continuing development of this application of MRI.
After an atherosclerotic vessel (or the plaque itself, as in carotid endarterectomy) is removed from the body, it can be imaged ex vivo at very high resolution. An example of image a rabbit artery (with pseudo coloring of the image in the lower panel) is shown here at the right. This represents a thin longitudinal slice through a highly diseased segment. With ex vivo imaging, various pulse sequences can be utilized to highlight different aspects of the atherosclerosis, without the time constraints of vivo imaging. The magic angle spinning (MAS) NMR data from the same segments, together with histology, will aid in interpretation of the fine details of the images.
A recent novel application is the use of image-guided NMR spectroscopy to detect the chemical signature of lipids within a small volume (1cc) in a plaque. Thus, as shown in the cover figure of JLR, we applied this combination method a carotid plaque (ex vivo) to show that the regions predicted to be lipid-rich (red) contained the major liquid lipid in plaques, cholesteryl ester.
We are also applying MRI to both mice and men. The remarkable resolution of high-field (11.7T) imaging in a narrow bore that can accommodate mice is shown in the image of the mouse vasculature in a live mouse.
At the other end of the spectrum, so to speak, we are imaging obese humans at 3T in a wide-bore clinical study of diabetes. The axial images show very bright regions from the subcutaneous fat (A and B), brightness around the heart (pericardial fat) in image A, and brightness in the liver (B). A view of the aortic artery (C) shows thickening from atherosclerosis. One of our current studies is examining the possible changes in such fat after a diet and exercise program.
James A. Hamitlon, Ph.D. firstname.lastname@example.org
Imaging Lab Manager
Jason Viereck, M.D., Ph.D. email@example.com
Biju Pillai, Ph.D. firstname.lastname@example.org
Kellen Fontanini, Ph.D. email@example.com
Kevin Hallock, Ph.D. firstname.lastname@example.org
Nasi Huang, M.D. email@example.com
Zhongjing Chen, Ph.D. firstname.lastname@example.org
Anthony Jay email@example.com
Ye Qiao firstname.lastname@example.org
Alkystis Phinikaridou email@example.com
Jun Cai firstname.lastname@example.org
Su Xu email@example.com
Eileen R. Krenzel firstname.lastname@example.org
Zifang Guo email@example.com
Ning Hua firstname.lastname@example.org
Jeffrey Simard – Max-Planck Institue, Germany
Christian Lucke – Johann Wolfgang Goethe-Universität Frankfurt
Shaoqing Peng – Lambda Solutions, Inc., Waltham, MA
Ji-Kyung Choi – Harvard Medical School/Massachusetts General Hospital
Fengli Zhang – CIMAR, NMR
Wen Guo – Boston University School of Medicine
Frits Kamp – Ludwig-Maximilians-Universität München, Germany
John Boylan – Boston College
Seiichi Era – Tokyo College of Pharmacy, Japan
Shastri Bhamidipati USDA
Jonathan Vural – Department of Physiology and Biophysics, Boston University
David H. Croll – Professor of Chemistry and Physics, Regis College, Weston, MA
Donna J. Cabral
Dr. David P. Cistola – Washington University School of Medicine
- Schettler, P.D., C.L. Van Antwerp, J.A. Hamilton, J.E. Thilly and J.D. Spear. “Impedence Behavior of Metal-Ammonia Solid Metal Interface” (1973) in Electrons in Fluids J. Jortner and N.R. Kestner, Eds., Springer-Verlag, Berlin, p. 239.
- Hamilton, J.A., C. Talkowski, E. Williams, E.M. Avila, A. Allerhand, E. Cordes and G. Camejo. Natural Abundance Carbon-13 Nuclear Magnetic Resonance Spectra of Human Serum Lipoproteins. (1973) Science 180:193-195.
- Williams, E., J.A. Hamilton, M.K. Jain, A. Allerhand, E.H. Cordes and S. Ochs. Natural Abundance Carbon-13 Nuclear Magnetic Resonance Spectra of the Canine Sciatic Nerve. (1973) Science 181:869-871.
- Rodulfo, T., J.A. Hamilton and E.H. Cordes. Secondary Valence Force Catalysis. IV. Polysoap Catalysis for the Alkaline Hydrolysis of p-Nitrophenyl Hexanoate” (1974) J. Org. Chem. 31:2281-2284.
- Hamilton, J.A., C. Talkowski, R.F. Childers, E. Williams, A. Allerhand and E.H. Cordes. Rotational and Segmental Motions in the Lipids of Human Plasma Lipoproteins. (1974) J. Biol. Chem. 249:4872-4878.
- Hamilton, J.A., N. Oppenheimer, R. Addleman, A. Clouse, E.H. Cordes and C.J. Glueck. High-field C-13 NMR Studies of b-VLDL of Type III Hyperlipoproteinemia Patients and of Normal Lipoproteins. (1976) Science 194:1424-1427.
- Hamilton, J.A., N. Oppenheimer and E.H. Cordes. Carbon-13 NMR Studies of Cholesteryl Esters and Cholesteryl Ester/Triglyceride Mixtures. (1977) J. Biol. Chem. 252:8071.
- Avila, E.M., J.A. Hamilton, C. Talkowski, J.A.K. Harmony, A. Allerhand, E.H. Cordes and G. Camejo. Structure of Plasma Lipoproteins. (1977) Act. Cient. V. 28: 37-43.
- Avila, E., J.A. Hamilton, J. Harmony, A. Allerhand and E.H. Cordes. Natural Abundance 13C Nuclear Magnetic Resonance Studies of Human Plasma High Density Lipoproteins. (1978) J. Biol. Chem. 253:3983-3987.
- Hamilton, J.A. and E.H. Cordes. Molecular Dynamics of Lipids in Human Plasma High-Density Lipoproteins: A High-field 13C NMR Study. (1978) J. Biol. Chem. 253:5193-5198.
- Hamilton, J.A., E.H. Cordes and C.J. Glueck. Lipid Dynamics in Human Low-Density Lipoproteins and Human Aortic Tissue with Fibrous Plaques: A Study by High-Field 13C NMR. (1979) J. Biol. Chem. 254:5435-5441.
- Brainard, J.R., J.A. Hamilton, E.H. Cordes, J.R. Patsch, A.M. Gotto and J.D Morrisett. Lipoprotein-X: 13C-NMR Studies on Native, Reconstituted and Model Systems. (1980) Biochemistry 19:4266-4273.
- Hamilton, J.A. and D.M. Small. Solubilization and Localization of Triolein in Phosphatidylcholine Bilayers: A Carbon-13 NMR Study. (1981) Proc. Natl. Acad. Sci. USA 78:878-6882.
- Bennett Clark, S., D. Atkinson, J.A. Hamilton, T. Forte, B. Russell, E.B. Feldman and D.M. Small. Physical Studies of d<1.006 g/ml Lymph Lipoproteins from Rats Fed Palmitate-Rich Diets. (1982) J. Lipid Res. 23:28-41.
- Cistola, D.P., D.M. Small and J.A. Hamilton. Ionization Behavior of Aqueous Short-Chain Carboxylic Acids: A Carbon-13 NMR Study. (1982) J. Lipid Res. 23:795-799.
- Hamilton, J.A. and D.M. Small. Solubilization and Localization of Cholesteryl Oleate in Egg Phosphatidylcholine Vesicles: A Carbon-13 NMR Study. (1982) J. Biol. Chem. 257:7318-7321.
- Ginsburg, G.S., D.M. Small and J.A. Hamilton. Temperature-Dependent Molecular Motions of Cholesterol Esters: A Carbon-13 Nuclear Magnetic Resonance Study. (1982) Biochemistry 21:6857-6867.
- Small, D.M., K. Miller, D. Cistola, G. Ginsburg, J. Parks, D. Atkinson and J.A. Hamilton. Physicochemical Studies on the Position of Molecules in Emulsions and Membranes. (1983) Bile Acids and Cholesterol in Health and Disease, G. Baumgartner, A. Stiehl and W. Gerok, eds., MTP Press Ltd., Boston, pp 25-30.
- Hamilton, J.A., D.M. Small and J. Parks. 1H NMR Studies of Monkey Triglyceride-Rich Lipoproteins. (1983) J. Biol. Chem. 258:1172-1179.
- Parks, J.S., D.P. Cistola, D.M. Small and J.A. Hamilton. Interactions of the Carboxyl Group of Oleic Acid with Bovine Serum Albumin: 13C NMR Study. (1983) J. Biol. Chem. 258:9262-9269.
- Hamilton, J.A., K.W. Miller and D.M. Small. Solubilization of Triolein and Cholesteryl Oleate in Egg Phosphatidylcholine Vesicles. (1983) J. Biol. Chem. 258:12821-12826.
- Hamilton, J.A., D.P. Cistola, J.D. Morrisett, J.R. Sparrow and D.M. Small. Interactions of Myristic Acid with Bovine Serum Albumin: A 13C NMR Study. (1984) Proc. Natl. Acad. Sci USA 81:3178-3722.
- Morrisett, J.D., J.W. Gaubatz, A.P. Tower, J.K. Allen, H.J. Pownall, P. Laggner and J.A. Hamilton. Thermotropic Properties and Molecular Dynamics of Cholesteryl Ester-Rich Very Low Density Lipoproteins. (1984) Biochemistry 23:5343-5352.
- Small, D.M., D.J. Cabral, D.P. Cistola, J.S. Parks and J.A. Hamilton. The Ionization Behavior of Fatty Acids and Bile Acids in Models and Membranes. (1984) Hepatology 4:77S-79S.
- Croll, D.H., D.M. Small and J.A. Hamilton. Molecular Motions and Thermotropic Phase Behavior of Cholesteryl Esters with Triolein. (1985) Biochemistry 24:7971-7980.
- Hamilton, J.A. and J.D. Morrisett. NMR Studies of Plasma Lipoproteins. (1986) Methods in Enzymology 28:472-515.
- Hamilton, J.A. and D.P. Cistola. Transfer of Oleic Acid between Albumin and Phospholipid Vesicles. (1986) Proc. Natl. Acad. Sci. USA 83:82-86.
- Cabral, D., D.M. Small and J.A. Hamilton. The Ionization Behavior of Bile Acids in Different Aqueous Environments. (1986) J. Lipid Res. 27:334-343.
- Cistola, D.P., D.M. Small, D. Atkinson and J.A. Hamilton. The Phase Behavior of Anhydrous and Hydrated 1:1 Fatty Acid-Soaps. (1986) Biochemistry 25:2804-2812.
- Croll, D., D.M. Small and J.A. Hamilton. Molecular Motions of Saturated Cholesteryl Esters. (1986) J. Chem. Phys. 85:7380-7387.
- Spooner, P.S., J.A. Hamilton, D.L. Gantz and D.M. Small. (1986) The Effect of Free Cholesterol on Solubilization of Cholesteryl Oleate in Phosphatidylcholine Bilayers: A 13C NMR Study. (1986) Biochim. Biophys. Acta 860:345-353.
- Cabral, D.J., D.M. Small, H.S. Lilly and J.A. Hamilton. Transbilayer Movement of Bile Acids in Model Membranes. (1987) Biochemistry 26:1801-1804.
- Small, D.M. and J.A. Hamilton. Can NMR Detect Cancer? (1987) New Eng. J. Med. 316:1411-1412.
- Cistola, D.P., D.M. Small and J.A. Hamilton. Carbon-13 NMR Studies of Saturated Fatty Acids Bound to Bovine Serum Albumin. I. The Filling of Individual Binding Sites. (1987) J. Biol. Chem. 262:10971-10979.
- Cistola, D.P., D.M. Small and J.A. Hamilton. Carbon-13 NMR Studies of Saturated Fatty Acids Bound to Bovine Serum Albumin. II. Electrostatic Interactions in Individual Fatty Acid Binding Sites. (1987) J. Biol. Chem. 262:10980-10985.
- Sripada, P.K., P.R. Maulik, J.A. Hamilton and G.G. Shipley. Partial-synthesis and Properties of a Series of N-acyl Sphingomyelins. (1987) J. Lipid Res. 28:710-718.
- Croll, D., P.K. Sripada and J.A. Hamilton. Temperature-Dependent Molecular Motions and Phase Behavior of Cholesteryl Ester Analogues. (1987) J. Lipid Res. 28:1444-1454.
- Cistola, D.P., M.T. Walsh, R.P. Corey, J.A. Hamilton and P. Brecher. Interactions of Oleic Acid with Liver Fatty Acid Binding Protein: A Carbon-13 NMR Study. (1988) Biochemistry 27:711-717.
- Cistola, D.P., J.A. Hamilton, D.M. Small and D. Jackson. The Ionization and Phase Behavior of Fatty Acids in Water: Application of the Gibbs Phase Rule. (1988) Biochemistry 27:1881-1888.
- Spooner, P.J.R., S. Bennett Clark, D.L. Gantz, J.A. Hamilton and D.M. Small. The Ionization and Distribution Behavior of Oleic Acid in Chylomicrons and Chylomicron-Like Emulsion Particles and the Influence of Serum Albumin. (1988) J. Biol. Chem. 263:1444-1453.
- Walsh, M.T., J.A. Hamilton, D. Atkinson and D.M. Small. Secondary and Tertiary Structure of Apolipoproteins. In Eicosanoids, Apolipoproteins, Lipoprotein Particles and Atherosclerosis. (Claude Malmendier, ed.) Plenum Publishing Co., New York NY (1988) pp 123-132.
- Hamilton, J.A. Interaction of Triglycerides with Phospholipids: Incorporation into the Bilayer Structure and Formation of Emulsions. (1989) Biochemistry 28:2514-2520.
- Hamilton, J.A. Medium Chain Fatty Acid Binding to Albumin and Transfer to Phospholipid Bilayers. (1989) Proc. Natl. Acad. Sci. 86:2663-2667.
- Bhamidipati, S.P. and J.A. Hamilton. Hydrolysis of a Phospholipid in an Inert Lipid Matrix by Phospholipase A2: A 13C NMR Study. (1989) Biochemistry 28:6667-6672.
- Deckelbaum, R.J., J.A. Hamilton, A. Moser, G. Bengtsson-Olivecrona, E. Butbul, Y. Carpentier, A. Gutman and T. Olivecrona. Medium Chain vs. Long Chain Triacylglycerol Emulsion Hydrolysis by Lipoprotein Lipase and Hepatic Lipase: Implications for the Mechanisms of Lipase Action. (1990) Biochemistry 29:1136-1142.
- Spooner, P.S., D.L. Gantz, J.A. Hamilton, and D.M. Small. The Distribution Behavior of Oleic Acid between a Chylomicron-Like Emulsion, Phospholipid Bilayer, and Serum Albumin. (1990) J. Biol. Chem. 265:12650-12655.
- Deshpande, M.S., J.G. Boylan and J.A. Hamilton. Inhibitors of Tissue Kallikrein, Based on the Structure of the Porcine Pancreatic Kallikrein/Aprotinin Complex. In Proceedings of the 11th American Peptide Symposium. (J. Rivier, ed.) Escom (1990).
- Hamilton, J.A., S. Bhamidipati, D. Kodali and D.M. Small. The Interfacial Conformation and Transbilayer Movement of Diacylglycerols in Phospholipid Bilayers. (1991) J. Biol. Chem. 266:1177-1186.
- Hamilton, J.A., S. Era, S.P. Bhamidipati and R.A. Reed. Oleic Acid Binding to Bovine Serum Albumin Fragments and Reassembled Albumin. (1991) Proc. Natl. Acad. Sci. USA 88:2051-2054.
- Hamilton, J.A., D.T. Fujito and C.F. Hammer. Solubilization and Localization of Weakly Polar Lipids in Unsonicated Egg Phosphatidylcholine: A 13C MAS-NMR Study. (1991) Biochemistry 30:2894-2902.
- Deshpande, M.S., J. Boylan, J.A. Hamilton and J. Burton. Conformation and Inhibitory Properties of Peptides Based on the Tissue Kallikrein-Aprotinin Complex. (1991) Internat. J. Peptides 37:536-543.
- Bhaskar, K.R., D. Gong, R. Bansil, S. Pajevic, J.A. Hamilton, B.S. Turner and J.T. LaMont. Profound Increase in Viscosity and Aggregation of Pig Gastric Mucin at Low pH. (1991) Gastroentereology 6827-6832.
- Boylan, J.G. and J.A. Hamilton. Interactions of acyl Coenzyme A with Phosphatidylcholine Bilayers and Serum Albumin. (1992) Biochemistry 31:557-567.
- Hamilton, J.A. Binding of Fatty Acids to Serum Albumin: A Case Study of Lipid-Protein Interactions. (1992) News in Physiological Sciences 7:264-270.
- Kamp, F. and J.A. Hamilton. pH Gradients Caused by Fast Flip-Flop of Un-ionized Fatty Acids in Phospholipid Bilayers. (1992) Proc. Natl. Acad. Sci. USA 89:11367-11370.
- Smith, Steven O., I. Kustanovich, S. Bhamidipati, A. Salmon and J.A. Hamilton. Interfacial Conformation of Dipalmitoylglycerol and Dipalmitoylphosphatidylcholine in Phospholipid Bilayers. (1992) Biochemistry 31:11660-11664.
- Kamp, F and JA Hamilton. Movement of Fatty Acids, Fatty Acid Analogues and Bile Acids across Phospholipid. Bilayer. Biochemistry. 1993 Oct 19;32(41):11074-86.
- Hamilton, JA, VN Civelek, F Kamp, K Tornheim, and BE Corkey. Changes in Internal pH Caused by Movement of Fatty Acids Into and Out Of Clonal Pancreatic Beta-Cells (HIT). J Biol Chem. 1994 Aug 19; 269(33):20852-6.
- Hamilton, JA. Studies of Minor Lipid Constituents of Membranes by High Resolution and Solid State 13C NMR Spectroscopy: Interactions with Phospholipid Bilayers and Transport Proteins. Chapter 4 in Carbon-13 Magnetic Resonance Spectroscopy. (N. Beckmann, ed.) Academic Press. 1995;117-57.
- Ho, JK, H Moser, Y Kishimoto, and JA Hamilton. Interactions of a Very Long Chain Fatty Acid with Model Membranes and Albumin: Implications for Adrenoleukodystrophy. J Clin Invest. 1995 Sep;96(3):1455-63.
- Lücke, C, F Zhang, H Rüterjans, JA Hamilton, and JC Sacchettini. Flexibility is a likely determinant of binding specificity in the case of ileal lipid binding protein. Structure. 1996 Jul 15;4(7):785-800.
- Civelek, VN, JA Hamilton, K Tornheim, KL Kelly, and BE Corkey. Intracellular pH in Adipocytes: Effects of Free Fatty Acid Diffusion and Insulin. Proc Natl Acad Sci USA. 1996 Sep 17;93(19): 10139-44.
- Zhang, F, C Lücke, LJ Baier, JC Sacchettini, and JA Hamilton. Solution Structure of human intestinal fatty acid binding protein: Implications for ligand entry and exit. J Biomol NMR. 1997 Apr;9(3): 213-28.
- Hamilton, JA. Fatty acid transport: difficult or easy? J Lipid Res. 1998 Mar;39, 467-81.
- Guo, W, JD Morrisett, GM Lawrie, ME DeBakey, and JA Hamilton. Identification of Different Lipid Phases and Calcium Phosphate Deposits in Human Carotid Artery Plaques by MAS NMR Spectroscopy. Magn Reson Med. 1998 Fed;39(2):184-9.
- Hamilton, JA. Transport of fatty acids across membranes by the diffusion mechanism. Prostaglandins Leuckot Essent Fatty Acids. 1999 May-Jun;60(5-6):291-7.
- Hamilton, JA and F Kamp. How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids? Diabetes. 1999 Dec;48(12):2255-69.
- Lücke, C, F Zhang, JA Hamilton, JC Sacchettini, and H Rüterjans. Solution Structure of Ileal Lipid binding Protein in Complex with Glycocholate. Eur J Biochem. 2000 May;267(10):2929-38.
- Guo, Wen, JD Morrisett, ME DeBakey, GM Lawrie, and JA Hamilton. Quantification in situ of crystalline cholesterol and calcium phosphate hydroxapatite in human atherosclerotic plaques by solid-state magic angle spinning NMR. Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1630-6.
- Peng, S, W Guo, JD Morrisett, MT Johnstone, and JA Hamilton. Quantification of Cholesteryl Esters in Human and Rabbit Atherosclerotic Plaques by Magic Angle Spinning 13C-NMR. Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2682-8.
- Johnstone, MT, RM Botnar, AS Perez, R Stewart, WC Quist, JA Hamilton, and WJ Manning. In vivo magnetic resonance imaging of experimental thrombosis in a rabbit model. Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1556-60.
- Guo, W, V Kurze, T Huber, NH Afdhal, K Beyer, and JA Hamilton. A solid-state NMR study of phospholipids-cholesterol interactions: sphingomyelin-cholesterol binary systems. Biophys J. 2002 Sep;83(3):1465-78.
- Lücke, C, N Kizilbash, HT van Moerkerk, JH Veerkamp, and JA Hamilton. NMR assignment and structural characterization of the fatty acid binding protein from the flight muscle of Locusta migratoria. J Biomol NMR. 2003 Apr;25(4):355-6.
- Lücke, C, LH Gutierrez-Gonzalez, and JA Hamilton. Intracellular lipid binding proteins: evolution, structure, and ligand binding. Cellular Proteins and Their Fatty Acids in Health and Disease. Dutta-Roy, Asim and Friedrich Spener (editors). Wiley-VCH 2003:95-114.
- Johnson, RA, JA Hamilton, TS Worgall, and RJ Deckelbaum. Free fatty acids modulate intermembrane trafficking of cholesterol by increasing lipid mobilities: novel 13C NMR analyses of free cholesterol partitioning. Biochemistry. 2003 Feb 18;42(6):1637-45.
- Kamp, F, W Guo, BE Corkey, and JA Hamilton. Rapid flip-flop of oleic acid across the plasma membrane of adipocytes. J Biol Chem. 2003 Mar 7;278(10):7988-95.
- Hamilton, JA. Fast flip-flop of cholesterol and fatty acids in membranes: implications for membrane transport proteins. Curr Opin Lipidol. 2003 Jun;14(3):263-71.
- Sharon, R, I Bar-Joseph, MP Frosch, DM Walsh, JA Hamilton, and DJ Selkoe. The Formation of Highly Soluble Oligomers of α-Synuclein is Regulated by Fatty Acids and Enhanced in Parkinson’s Disease. Neuron. 2003 Feb 20;37(4):583-95.
- Zhang, F, C Lücke, LJ Baier, JC Sacchettinni, and JA Hamilton. Solution structure of human intestinal fatty acid binding protein with a naturally-occurring single amino acid substitution (A54T) that is associated with altered lipid metabolism. Biochemistry. 2003 Jun24;42(24):7339-47.
- Pownall, H and JA Hamilton. Biophysical mechanisms of fatty acid transport across membranes. The Lipobiology Volume. Ger van der Vusse (editor). Elsevier Science & Technology 2003:33,153-73.
- Kamp, F, N Kizilbash, BE Corkey, PO Berggren, and JA Hamilton. Sulfonylureas rapidly cross phospholipid bilayer membranes by a free-diffusion mechanism. Diabetes. 2003 Oct;52(10):2526-31.
- Hamilton, JA. Fatty acid interactions with proteins: what X-ray crystal and NMR solution structures tell us. Prog Lipid Res. 2004 May;43(3):177-99.
- Botnar, RM, AS Perez, S Witte, AJ Wiethoff, J Laredo, JA Hamilton, W Quist, EC Parsons Jr, A Vaidya, A Kolodziej, JA Barrett, PB Graham, RM Weisskoff, WJ Manning, and MT Johnstone. In Vivo Molecular Imaging of Acute and Subacute Thrombosis Using a Fibrin-Binding Magnetic Resonance Imaging Contrast Agent. Circulation 2004 Apr 27;109(16):2023-9.
- Johnstone, MT, AS Perez, I Nasser, R Stewart, A Vaidya, F Al Ammary, B Schmidt, G Horowitz, J Dolgoff, JA Hamilton, and WC Quist. Angiotensin Receptor Blockade with Candesartan Attenuates Atherosclerosis, Plaque Disruption, and Macrophage Accumulation Within the Plaque in a Rabbit Model. Circulation. 2004 Oct 5;110(14):2060-5.
- Simard, JR, PA Zunszain, CE Ha, JS Yang, NV Bhagavan, I Petitpas, S Curry, and JA Hamilton. Locating high-affinity fatty acid-binding sites on albumin by x-ray crystallography and NMR spectroscopy. Proc Natl Acad Sci USA. 2005 Dec 13;102(50):17958-63.
- Ruberg, FL, J Viereck, A Phinikaridou, Y Qiao, J Loscalzo, and JA Hamilton. Identification of cholesteryl esters in human carotid atherosclerosis by ex vivo image-guided proton MRS. J Lipid Res. 2006 Feb;47(2):310-7.
- Guo, W, N Huang, J Cai, W Xie, and JA Hamilton. Fatty acid transport and metabolism in HepG2 Cells. Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G528-34
- Simard, JR, PA Zunszain, JA Hamilton, and S Curry. Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis. J Mol Biol. 2006 Aug 11;361(2):336-51.
- Kamp, F and JA Hamilton. How fatty acids of different chain length enter and leave cells by free diffusion. Prostaglandins Leukot Essent Fatty Acids. 2006 Sep;75(3):149-59.
- Lücke, C, Y Qiao, HT van Moerkerk, JH Veerkamp, and JA Hamilton. Fatty-acid-binding protein from the flight muscle of Locusta migratoria: evolutionary variations in fatty acid binding. Biochemistry. 2006 May 23;45(20):6296-305.
- Lücke, C, DL Gantz, E Klimtchuk, and JA Hamilton. Interactions between fatty acids and alpha-synuclein. J Lipid Res. 2006 Aug;47(8):1714-24.
- Meshulam, T, JR Simard, J Wharton, JA Hamilton, and PF Pilch. Role of caveolin-1 and cholesterol in transmembrane fatty acid movement. Biochemistry. 2006 Mar 7;45(9):2882-93.
- Xie, W, JA Hamilton, JL Kirkland, BE Corkey, and W Guo. Oleate-induced formation of fat cells with impaired insulin sensitivity. Lipids. 2006 Mar;41(3):267-71.
- Hamilton, JA and RD Deckelbaum. Crystal structure of CETP: new hopes for raising HDL to decrease risk of cardiovascular disease? Nat Struct Mol Biol. 2007 Feb;14(2):106-13.
- Qiao, Y, I Ronen, J Viereck, FL Ruberg, and JA Hamilton. Identification of Atherosclerotic Lipid Deposits by Diffusion-Weighted Imaging. Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1440-6.
- Ziouzenkova, O, G Orasanu, M Sharlach, TE Akiyama, JP Berger, J Viereck, JA Hamilton, G Tang, GG Dolnikowski, and J Plutzky. Retinaldehyde inhibits adipogenesis and regulates activation of RXR heterodimers. Nat Med. 2007;(6):695-702.
- Duncanson, WJ, MA Figa, K Hallock, S Zalipsky, JA Hamilton, and JY Wong. Targeted binding of PLA microparticles with lipid-PEG-tethered ligands. Biomaterials. 2007 Nov;28(33):4991-9.
- Hamilton, JA and K Brunaldi. A model for fatty acid transport into the brain. J Mol Neurosci. 2007 Sep;33(1):12-7.
- Hamilton, JA, CJ Hillard, AA Spector, and PA Watkins. Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disorders. J Mol Neurosci. 2007 Sep;33(1):2-11.
- Hamilton, JA. New insights into the roles of proteins and lipids in membrane transport of fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):355-61.
- Brunaldi, K, JR Simard, F Kamp, C Rewal, T Asawakarn, P O’Shea, and JA Hamilton. Fluorescence assays for measuring fatty acid binding and transport through membranes. Methods Mol Biol. 2007;400:237-55.
- Simard, JR, F Kamp, and JA Hamilton. Acrylodan-labeled intestinal fatty acid-binding protein to measure concentrations of unbound fatty acids. Methods Mol Biol. 2007;400:27-43.
- Simard, JR, F Kamp, and JA Hamilton. Measuring the adsorption of fatty acids to phospholipid vesicles by multiple fluorescence probes. Biophys J. 2008 Jun;94(11)4493-503.
- Gupta, V, S Bhasin, W Guo, R Singh, R Miki, P Chauhan, K Choong, T Tchkonia, NK Lebrasseur, JN Flanagan, JA Hamilton, JC Viereck, NS Narula, JL Kirkland, and R Jasuja. Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Mol Cell Endocrinol. 2008 Dec 16;296(1-2):32-40.
- Simard, JR, BK Pillai, and JA Hamilton. Fatty acid flip-flop in a model membrane is faster than desorption into the aqueous phase. Biochemistry. 2008 Sep 2;47(35):9081-9.
- Watkins, PA and JA Hamilton. Roundtable discussion of session 1: mechanisms of lipid uptake and transport in the brain. J Mol Neurosci. 2007 Sep;33(1):45-50.
- Watkins, PA and JA Hamilton. Roundtable discussion of session 2: lipoproteins and polyunsaturated fatty acids. J Mol Neurosci. 2007 Sep;33(1):74-9.
- Watkins, PA and JA Hamilton. Roundtable discussion of session 3: eicosanoids in brain function. J Mol Neurosci. 2007 Sep;33(1):100-4.
- Watkins, PA and JA Hamilton. Roundtable discussion of session 4: fatty acids and lipids in brain disorders. J Mol Neurosci. 2007 Sep;33(1):120-4.
- Katz, R, JA Hamilton, HJ Pownall, RJ Deckelbaum, CJ Hillard, RC Leboeuf, and PA Watkins. Brain uptake and utilization of fatty acids, lipids & lipoproteins: recommendations for future research. J Mol Neurosci. 2007 Sep;33(1):146-50.
- Izumiya, Y, T Hopkins, C Morris, K Sato, L Zeng, J Viereck, JA Hamilton, N Ouchi, NK LeBrasseur, and K Walsh. Fast/Glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 2008 Feb;7(2):159-72.
- Qiao, Y, A Farber, E Semaan, and JA Hamilton. Images in cardiovascular medicine. Healing of an asymptomatic carotid plaque ulceration. Circulation. 2008 Sep 2;118(10):e147-8.
- Phinikaridou, A, KJ Hallock, Y Qiao, and JA Hamilton. A robust rabbit model of human atherosclerosis and atherothrombosis. J Lipid Res. 2009 May;50(5):787-97.
- Decano, JL, JC Viereck, AC McKee, JA Hamilton, N Ruiz-Opazo, and VL Herrera. Early-life sodium exposure unmasks susceptibility to stroke in hyperlipidemic, hypertensive heterozygous Tg25 rats transgenic for human cholesteryl ester transfer protein. Circulation. 2009 Mar 24;119(11):1501-9.
- Simard, JR, T Meshulam, BK Pillai, MT Kirber, K Brunaldi, S Xu, PF Pilch, and JA Hamilton. Caveolins sequester fatty acids on the cytoplasmic leaflet of the plasma membrane, augment triglyceride formation and protect cells from lipotoxicity. J Lipid Res. 2009 Jul 15 [Epub ahead of print].
- Tu, P, S Bhasin, PW Hruz, KL Herbst, LW Castellani, N Hua, JA Hamilton, and W Guo. Genetic disruption of myostatin reduces the development of proatherogenic dyslipidemia and atherogenic lesions in Ldlr null mice. Diabetes. 2009 Aug; 58(8):1739-48.
- Pillai, BK, R Jasuja, JR Simard, and JA Hamilton. Fast diffusion of very long chain saturated fatty acids across a bilayer membrane and their rapid extraction by cyclodextrins: Implications for adrenoleukodystrophy. J Biol Chem. 2009 Nov 27;284(48):33296-304.
- Frederick L. Ruberg, Zhongjing Chen, Sherman Bigornia, Zifang Guo, Kevin Hallock, Ning Huang, Hernan Jara, Michael LaValley, Alkystis Phinikaridou, Ye Qiao, Jason Viereck, Caroline M. Apovian, James. A. Hamilton. Differing relationship of body size to pericardial fat volume, cardiac function, and insulin sensitivity in obesity and metabolic syndrome. Obesity 2009 Oct 29. [Epub ahead of print] PMID: 19875992.
- Brunaldi, K, N Huang, and JA Hamilton. Fatty acids are rapidly delivered to and extracted from membranes by methyl-b-cyclodextrin. J Lipid Res. 2010 Jan; 51(1):120-31.
- Phinikaridou A, Ruberg FL, Hallock KJ, Qiao Y, Hua N, Viereck JC, Hamilton JA. In vivo Detection of Vulnerable Atherosclerotic Plaque by Magnetic Resonance Imaging in a Rabbit Model.Circ Cardiovasc Imaging. 2010 Mar 1. [Epub ahead of print] PMID: 20194634
- Hayashi C, Viereck J, Hua N, Phinikaridou A, Madrigal AG, Gibson FC 3rd, Hamilton JA, Genco CA Porphyromonas gingivalis accelerates inflammatory atherosclerosis in the innominate artery of ApoE deficient mice. Atherosclerosis. 2010 Dec 22. [Epub ahead of print]
- Simard, J. R., Meshulam, T., Pillai, B. K., Kirber, M. T., Brunaldi, K., Xu, S., Pilch, P. F., et al. (2010). Caveolins sequester FA on the cytoplasmic leaflet of the plasma membrane, augment triglyceride formation, and protect cells from lipotoxicity. Journal of lipid research, 51(5), 914–922. doi:10.1194/jlr.M900251
- Anderson SW, Soto JA, Milch HN, Ozonoff A, O’Brien M, Hamilton JA, Jara HJ. The Effect of Disease Progression on Liver ADC Values in a Murine Model of NASH at 11.7T MRI. JMRI, In Press.
- Anderson SW, Jara HJ, Ozonoff A, O’Brien M, Hamilton JA, Soto JA. The Effect of Disease Progression on Liver ADC and T2 Values in a Murine Model of Hepatic Fibrosis at 11.7T MRI. JMRI, 2010 Jan 23(10:140-6.
- Qiao, Y., Hallock, K. J., & Hamilton, J. A. (2011). Magnetization Transfer Magnetic Resonance of Human Atherosclerotic Plaques ex vivo Detects Areas of High Protein Density. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance, 13(1), 73. doi:10.1186/1532-429X-13-73
- Phinikaridou, A., & Hamilton, J. A. (2011). Application of MRI to detect high-risk atherosclerotic plaque. Expert review of cardiovascular therapy, 9(5), 545–550. doi:10.1586/erc.11.31
- Souza, S. L., Hallock, K. J., Funari, S. S., Vaz, W. L. C., Hamilton, J. A., & Melo, E. (2011). Study of the miscibility of cholesteryl oleate in a matrix of ceramide, cholesterol and fatty acid. Chemistry and physics of lipids, 164(7), 664–671. doi:10.1016/j.chemphyslip.2011.06.011
|Birthdate||October 21, 1947|
|1969-1974||Indiana University, Ph.D.|
|Positions||Summer 1969||Research Chemist, Eastman Kodak|
|1969-1974||Associate Instructor, Indiana University|
|1971-1974||Research Assistant, Indiana University|
|1975||Postdoctoral Biochemistry Trainee|
|Fall term 1975||Assistant Professor of Continuing Education in Chemistry, Indiana University|
|May 1976||Visiting Scientist, Juniata College|
|1976-1978||NIH Postdoctoral Fellow, Indiana University|
|1978-present||Director of NMR Facility, Biophysics Institute/Department, Boston University School of Medicine|
|1978-1985||Assistant Research Professor of Medicine and Biochemistry, BUSM|
|1986-present||Associate Research Professor of Medicine and Biochemistry, BUSM|
|1989-1991||Associate Professor of Biophysics, BUSM|
|1991-present||Professor of Biophysics, BUSM|
|2000-present||Director, Cardiovascular Magnetic Resonance Imaging and Spectroscopy Lab|
|2006-present||Professor of Bioengineering, Boston University|
|Honors||Cum Laude graduate, Juniata College, 1969|
|Dr. Andrew B. and Maria F. Brumbaugh Science Prize, Juniata College|
|Juniata College Honor Society|
|National Research Fellowship Award (NIH Postdoctoral), 1976|
|International Who’s Who in Education|
|International Men of Achievement|
|American Men and Women of Science|
|Who’s Who in Science and Engineering|
|Who’s Who in Frontiers of Science and Technology|
|Who’s Who in the East|
|Journals||Lipids, Associate Editor, 1990-|
|J. Lipid Research, Guest Associate Editor, 1993-1994|
|J. Lipid Research, Editorial Board, 1995-|
|Obesity research, Associate Editor 2004-present|
|Societies||Biophysical Society American Chemical Society|
James A. Hamilton
Department of Physiology and Biophysics
Boston University School of Medicine
700 Albany Street, W302
Boston MA 02118-2526
Fax: (617) 638-4041