James A. Hamilton, Ph.D.

Research

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.

The Group

Principal Investigator	James A. Hamitlon, Ph.D.	jhamilt@bu.edu
Imaging Lab Manager	Jason Viereck, M.D., Ph.D.	jason.viereck@bmc.org
Postdoctoral Fellows	Biju Pillai, Ph.D.	biju@bu.edu
	Kellen Fontanini, Ph.D.	hellenf@bu.edu
	Kevin Hallock, Ph.D.	hallockk@bu.edu
	Nasi Huang, M.D.	nasi@bu.edu
	Zhongjing Chen, Ph.D.	zchen@bu.edu
Graduate Students	Ye Qiao	qiaoyale@bu.edu
	Alkystis Phinikaridou	alkystis@bu.edu
	Jun Cai	caijun@bu.edu
	Su Xu	xusu@bu.edu
	Eileen R. Krenzel	ekrenzel@bu.edu
	Zifang Guo	zfguo@bu.edu
	Ning Hua	huaning@bu.edu
Alumni	Elena Klimtchuk
	Jeffrey Simard	Max-Planck Institue, Germany
	Charu Rewal
	Volker Kurze
	Christian Lucke	Johann Wolfgang Goethe-Universität Frankfurt
	Shaoqing Peng	Lambda Solutions, Inc., Waltham, MA
	ZhaoXing Sun
	Nadeem Kizilbash
	Ji-Kyung Choi	Harvard Medical School/Massachusetts General Hospital
	Shekar
	Rajini Anachi
	Frank Caserta
	Fengli Zhang	CIMAR, NMR
	Jet Ho
	Wen Guo	Boston University School of Medicine
	Frits Kamp	Ludwig-Maximilians-Universität München, Germany
	Amir Salmon
	John Boylan	Boston College
	Marie Kenyon
	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
	Howard Lilly
	Dr. David P. Cistola	Washington University School of Medicine

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Publications

1.         Hamilton, J.A., C. Talkowski, E. Williams, E.M. Avila, A. Allerhand, E.H. Cordes, and G. Camejo. 1973. Natural Abundance Carbon-13 Nuclear Magnetic Resonance Spectra of Human Serum Lipoproteins. Science. 180 (82):193-5.

2.         Williams, E., J.A. Hamilton, M.K. Jain, A. Allerhand, E.H. Cordes, and S. Ochs. 1973. Natural Abundance Carbon-13 Nuclear Magnetic Resonance Spectra of the Canine Sciatic Nerve. Science. 181 (102):869-71.

3.         Hamilton, J.A., C. Talkowski, R.F. Childers, E. Williams, A. Allerhand, and E.H. Cordes. 1974. Rotational and Segmental Motions in the Lipids of Human Plasma Lipoproteins. J Biol Chem. 249 (15):4872-8.

4.         Hamilton, J.A., N.J. Oppenheimer, R. Addleman, A.O. Clouse, E.H. Cordes, P.M. Steiner, and C.J. Glueck. 1976. High-Field 13c Nmr Studies of Certain Normal and Abnormal Human Plasma Lipoproteins. Science. 194 (4272):1424-7.

5.         Avila-Bello, E.M., J.A. Hamilton, C. Talkowski, J.A. Harmony, A. Allerhand, E.H. Cordes, and G. Camejo. 1977. [Structure of Plasma Lipoproteins (Author's Transl)]. Acta Cient Venez 28 (1):37-43.

6.         Hamilton, J.A., N. Oppenheimer, and E.H. Cordes. 1977. Carbon-13 Nuclear Magnetic Resonance Studies of Cholesteryl Esters and Cholesteryl Ester/Triglyceride Mixtures. J Biol Chem. 252 (22):8071-80.

7.         Avila, E.M., J.A. Hamilton, J.A. Harmony, A. Allerhand, and E.H. Cordes. 1978. Natural Abundance 13c Nuclear Magnetic Resonance Studies of Human Plasma High Density Lipoproteins. J Biol Chem. 253 (11):3983-7.

8.         Hamilton, J.A., and E.H. Cordes. 1978. Molecular Dynamics of Lipids in Human Plasma High Density Lipoproteins. A High Field 13c Nmr Study. J Biol Chem. 253 (14):5193-8.

9.         Hamilton, J.A., E.H. Cordes, and C.J. Glueck. 1979. Lipid Dynamics in Human Low Density Lipoproteins and Human Aortic Tissue with Fibrous Plaques. A Study by High Field 13c Nmr Spectroscopy. J Biol Chem. 254 (12):5435-41.

10.       Brainard, J.R., J.A. Hamilton, E.H. Cordes, J.R. Patsch, A.M. Gotto, Jr., and J.D. Morrisett. 1980. Lipoprotein-X: Carbon-13 Nuclear Magnetic Resonance Studies on Native, Reconstituted, and Model Systems. Biochemistry. 19 (18):4266-73.

11.       Hamilton, J.A., and D.M. Small. 1981. Solubilization and Localization of Triolein in Phosphatidylcholine Bilayers: A 13c Nmr Study. Proc Natl Acad Sci U S A. 78 (11):6878-82.

12.       Cistola, D.P., D.M. Small, and J.A. Hamilton. 1982. Ionization Behavior of Aqueous Short-Chain Carboxylic Acids: A Carbon-13 Nmr Study. J Lipid Res. 23 (5):795-9.

13.       Clark, S.B., D. Atkinson, J.A. Hamilton, T. Forte, B. Russell, E.B. Feldman, and D.M. Small. 1982. Physical Studies of D Less Than 1.006 G/Ml Lymph Lipoproteins from Rats Fed Palmitate-Rich Diets. J Lipid Res. 23 (1):28-41.

14.       Ginsburg, G.S., D.M. Small, and J.A. Hamilton. 1982. Temperature-Dependent Molecular Motions of Cholesterol Esters: A Carbon-13 Nuclear Magnetic Resonance Study. Biochemistry. 21 (26):6857-67.

15.       Hamilton, J.A., and D.M. Small. 1982. Solubilization and Localization of Cholesteryl Oleate in Egg Phosphatidylcholine Vesicles. A Carbon 13 Nmr Study. J Biol Chem. 257 (13):7318-21.

16.       Hamilton, J.A., K.W. Miller, and D.M. Small. 1983. Solubilization of Triolein and Cholesteryl Oleate in Egg Phosphatidylcholine Vesicles. Journal Of Biological Chemistry 258 (21):2821-6.

17.       Parks, J.S., D.P. Cistola, D.M. Small, and J.A. Hamilton. 1983. Interactions of the Carboxyl Group of Oleic-Acid with Bovine Serum-Albumin - a C-13 Nmr-Study. Journal Of Biological Chemistry 258 (15):9262-9.

18.       Hamilton, J.A., D.M. Small, and J.S. Parks. 1983. H-1-Nmr Studies of Lymph Chylomicra and Very Low-Density Lipoproteins from Non-Human Primates. Journal Of Biological Chemistry 258 (2):1172-9.

19.       Small, D.M., D.J. Cabral, D.P. Cistola, J.S. Parks, and J.A. Hamilton. 1984. The Ionization Behavior of Fatty-Acids and Bile-Acids in Micelles and Membranes. Hepatology 4 (5):S77-S9.

20.       Morrisett, J.D., J.W. Gaubatz, A.P. Tarver, J.K. Allen, H.J. Pownall, P. Laggner, and J.A. Hamilton. 1984. Thermotropic Properties and Molecular-Dynamics of Cholesteryl Ester Rich Very Low-Density Lipoproteins - Effect of Hydrophobic Core on Polar Surface. Biochemistry 23 (22):5343-52.

21.       Hamilton, J.A., D.P. Cistola, J.D. Morrisett, J.T. Sparrow, and D.M. Small. 1984. Interactions of Myristic Acid with Bovine Serum-Albumin - a C-13 Nmr-Study. Proceedings Of The National Academy Of Sciences Of The United States Of America-Biological Sciences 81 (12):3718-22.

22.       Croll, D.H., D.M. Small, and J.A. Hamilton. 1985. Molecular Motions and Thermotropic Phase-Behavior of Cholesteryl Esters with Triolein. Biochemistry 24 (27):7971-80.

23.       Croll, D.H., D.M. Small, and J.A. Hamilton. 1986. Temperature-Dependent Molecular Motions of Saturated Acyl Cholesteryl Esters - a C-13 Nmr-Study. Journal Of Chemical Physics 85 (12):7380-7.

24.       Spooner, P.J.R., J.A. Hamilton, D.L. Gantz, and D.M. Small. 1986. The Effect of Free-Cholesterol on the Solubilization of Cholesteryl Oleate in Phosphatidylcholine Bilayers - a C-13-Nmr Study. Biochimica Et Biophysica Acta 860 (2):345-53.

25.       Hamilton, J.A., and J.D. Morrisett. 1986. Nuclear-Magnetic-Resonance Studies of Lipoproteins. Methods In Enzymology 128:472-515.

26.       Cistola, D.P., D. Atkinson, J.A. Hamilton, and D.M. Small. 1986. Phase-Behavior and Bilayer Properties of Fatty-Acids - Hydrated 1-1 Acid Soaps. Biochemistry 25 (10):2804-12.

27.       Cabral, D.J., J.A. Hamilton, and D.M. Small. 1986. The Ionization Behavior of Bile-Acids in Different Aqueous Environments. Journal Of Lipid Research 27 (3):334-43.

28.       Hamilton, J.A., and D.P. Cistola. 1986. Transfer of Oleic-Acid between Albumin and Phospholipid-Vesicles. Proceedings Of The National Academy Of Sciences Of The United States Of America 83 (1):82-6.

29.       Croll, D.H., P.K. Sripada, and J.A. Hamilton. 1987. Temperature-Dependent Molecular Motions and Phase-Behavior of Cholesteryl Ester Analogs. Journal Of Lipid Research 28 (12):1444-54.

30.       Cistola, D.P., D.M. Small, and J.A. Hamilton. 1987. C-13 Nmr-Studies of Saturated Fatty-Acids Bound to Bovine Serum-Albumin.1. The Filling of Individual Fatty-Acid Binding-Sites. Journal Of Biological Chemistry 262 (23):10971-9.

31.       Cistola, D.P., D.M. Small, and J.A. Hamilton. 1987. C-13 Nmr-Studies of Saturated Fatty-Acids Bound to Bovine Serum-Albumin.2. Electrostatic Interactions in Individual Fatty-Acid Binding-Sites. Journal Of Biological Chemistry 262 (23):10980-5.

32.       Sripada, P.K., P.R. Maulik, J.A. Hamilton, and G.G. Shipley. 1987. Partial Synthesis and Properties of a Series of N-Acyl Sphingomyelins. Journal Of Lipid Research 28 (6):710-8.

33.       Small, D.M., and J.A. Hamilton. 1987. Detection of Malignant-Tumors by Nuclear-Magnetic-Resonance Spectroscopy of Plasma. New England Journal Of Medicine 316 (22):1412-3.

34.       Cabral, D.J., D.M. Small, H.S. Lilly, and J.A. Hamilton. 1987. Transbilayer Movement of Bile-Acids in Model Membranes. Biochemistry 26 (7):1801-4.

35.       Cistola, D.P., J.A. Hamilton, D. Jackson, and D.M. Small. 1988. Ionization and Phase-Behavior of Fatty-Acids in Water - Application of the Gibbs Phase Rule. Biochemistry 27 (6):1881-8.

36.       Cistola, D.P., M.T. Walsh, R.P. Corey, J.A. Hamilton, and P. Brecher. 1988. Interactions of Oleic-Acid with Liver Fatty-Acid Binding-Protein - a C-13 Nmr-Study. Biochemistry 27 (2):711-7.

37.       Spooner, P.J.R., S.B. Clark, D.L. Gantz, J.A. Hamilton, and D.M. Small. 1988. The Ionization and Distribution Behavior of Oleic-Acid in Chylomicrons and Chylomicron-Like Emulsion Particles and the Influence of Serum-Albumin. Journal Of Biological Chemistry 263 (3):1444-53.

38.       Bhamidipati, S.P., and J.A. Hamilton. 1989. Hydrolysis of a Phospholipid in an Inert Lipid Matrix by Phospholipase A2- a C-13 Nmr-Study. Biochemistry 28 (16):6667-72.

39.       Hamilton, J.A. 1989. Medium-Chain Fatty-Acid Binding to Albumin and Transfer to Phospholipid-Bilayers. Proceedings Of The National Academy Of Sciences Of The United States Of America 86 (8):2663-7.

40.       Hamilton, J.A. 1989. Interactions of Triglycerides with Phospholipids - Incorporation into the Bilayer Structure and Formation of Emulsions. Biochemistry 28 (6):2514-20.

41.       Spooner, P.J.R., D.L. Gantz, J.A. Hamilton, and D.M. Small. 1990. The Distribution of Oleic-Acid between Chylomicron-Like Emulsions, Phospholipid-Bilayers, and Serum-Albumin - a Model for Fatty-Acid Distribution between Lipoproteins, Membranes, and Albumin. Journal Of Biological Chemistry 265 (21):12650-5.

42.       Deckelbaum, R.J., J.A. Hamilton, A. Moser, G. Bengtssonolivecrona, E. Butbul, Y.A. Carpentier, A. Gutman, and T. Olivecrona. 1990. Medium-Chain Versus Long-Chain Triacylglycerol Emulsion Hydrolysis by Lipoprotein-Lipase and Hepatic Lipase - Implications for the Mechanisms of Lipase Action. Biochemistry 29 (5):1136-42.

43.       Bhaskar, K.R., D. Gong, R. Bansil, S. Pajevic, J.A. Hamilton, B.S. Turner, and J.T. Lamont. 1991. Profound Increase in Viscosity and Aggregation of Pig Gastric Mucin at Low Ph. American Journal Of Physiology 261 (5):G827-G33.

44.       Deshpande, M.S., J. Boylan, J.A. Hamilton, and J. Burton. 1991. Conformation and Inhibitory Properties of Peptides Based on the Tissue Kallikrein-Aprotinin Complex. International Journal Of Peptide And Protein Research 37 (6):536-43.

45.       Hamilton, J.A., D.T. Fujito, and C.F. Hammer. 1991. Solubilization and Localization of Weakly Polar Lipids in Unsonicated Egg Phosphatidylcholine - a C-13 Mas Nmr-Study. Biochemistry 30 (11):2894-902.

46.       Hamilton, J.A., S. Era, S.P. Bhamidipati, and R.G. Reed. 1991. Locations of the 3 Primary Binding-Sites for Long-Chain Fatty-Acids on Bovine Serum-Albumin. Proceedings Of The National Academy Of Sciences Of The United States Of America 88 (6):2051-4.

47.       Hamilton, J.A., S.P. Bhamidipati, D.R. Kodali, and D.M. Small. 1991. The Interfacial Conformation and Transbilayer Movement of Diacylglycerols in Phospholipid-Bilayers. Journal Of Biological Chemistry 266 (2):1177-86.

48.       Hamilton, J.A. 1992. Binding of Fatty-Acids to Albumin - a Case-Study of Lipid-Protein Interactions. News In Physiological Sciences 7:264-70.

49.       Kamp, F., and J.A. Hamilton. 1992. Ph Gradients across Phospholipid-Membranes Caused by Fast Flip-Flop of Unionized Fatty-Acids. Proceedings Of The National Academy Of Sciences Of The United States Of America 89 (23):11367-70.

50.       Smith, S.O., I. Kustanovich, S. Bhamidipati, A. Salmon, and J.A. Hamilton. 1992. Interfacial Conformation of Dipalmitoylglycerol and Dipalmitoylphosphatidylcholine in Phospholipid-Bilayers. Biochemistry 31 (46):11660-4.

51.       Boylan, J.G., and J.A. Hamilton. 1992. Interactions of Acyl-Coenzyme-a with Phosphatidylcholine Bilayers and Serum-Albumin. Biochemistry 31 (2):557-67.

52.       Kamp, F., H.V. Westerhoff, and J.A. Hamilton. 1993. Movement of Fatty-Acids, Fatty-Acid Analogs, and Bile-Acids across Phospholipid-Bilayers - Kinetics of Fatty Acid-Mediated Proton Movement across Small Unilamellar Vesicles. Biochemistry 32 (41):11074-86.

53.       Guo, W., and J.A. Hamilton. 1993. Molecular-Organization and Motions of Cholesteryl Esters in Crystalline and Liquid-Crystalline Phases - a C-13 and H-1 Magic-Angle-Spinning Nmr-Study. Biochemistry 32 (35):9038-52.

54.       Bhamidipati, S.P., and J.A. Hamilton. 1993. Nmr-Studies of Phospholipase-C Hydrolysis of Phosphatidylcholine in Model Membranes. Journal Of Biological Chemistry 268 (4):2431-4.

55.       Hamilton, J.A., V.N. Civelek, F. Kamp, K. Tornheim, and B.E. Corkey. 1994. Changes in Internal Ph Caused by Movement of Fatty-Acids into and out of Clonal Pancreatic Beta-Cells (Hit). Journal Of Biological Chemistry 269 (33):20852-6.

56.       Johnson, W.C., M.T. Watkins, J. Hamilton, D. Baldwin, and N. Walker. 1994. Pentoxifylline Therapy for Chronic Claudication - Are Patients Dependent on Therapy. Surgery 115 (6):735-9.

57.       Smith, S.O., J. Hamilton, A. Salmon, and B.J. Bormann. 1994. Rotational Resonance Nmr Determination of Intramolecular and Intermolecular Distance Constraints in Dipalmitoylphosphatidylcholine Bilayers. Biochemistry 33 (20):6327-33.

58.       Ko, J., J.A. Hamilton, H.T. Tonnu, C.D. Schteingart, A.F. Hofmann, and D.M. Small. 1994. Effects of Side-Chain Length on Ionization Behavior and Transbilayer Transport of Unconjugated Dihydroxy Bile-Acids - a Comparison of nor-Chenodeoxycholic Acid and Chenodeoxycholic Acid. Journal Of Lipid Research 35 (5):883-92.

59.       Kenyon, M.A., and J.A. Hamilton. 1994. C-13 Nmr-Studies of the Binding of Medium-Chain Fatty-Acids to Human Serum-Albumin. Journal Of Lipid Research 35 (3):458-67.

60.       Petrou, S., R.W. Ordway, J.A. Hamilton, J.V. Walsh, and J.J. Singer. 1994. Structural Requirements for Charged Lipid Molecules to Directly Increase or Suppress K+ Channel Activity in Smooth-Muscle Cells - Effects of Fatty-Acids, Lysophosphatidate, Acyl Coenzyme-a and Sphingosine. Journal Of General Physiology 103 (3):471-86.

61.       Salmon, A., and J.A. Hamilton. 1995. Magic-Angle Spinning and Solution C-13 Nuclear Magnetic Resonance Studies of Medium- and Long-Chain Cholesteryl Esters in Model Bilayers. Biochemistry 34 (49):16065-73.

62.       Guo, W., and J.A. Hamilton. 1995. A Multinuclear Solid-State Nmr-Study of Phospholipid-Cholesterol Interactions - Dipalmitoylphosphatidylcholine-Cholesterol Binary-System. Biochemistry 34 (43):14174-84.

63.       Kamp, F., D. Zakim, F.L. Zhang, N. Noy, and J.A. Hamilton. 1995. Fatty-Acid Flip-Flop in Phospholipid-Bilayers Is Extremely Fast. Biochemistry 34 (37):11928-37.

64.       Ho, J.K., H. Moser, Y. Kishimoto, and J.A. Hamilton. 1995. Interactions of a Very Long-Chain Fatty-Acid with Model Membranes and Serum-Albumin - Implications for the Pathogenesis of Adrenoleukodystrophy. Journal Of Clinical Investigation 96 (3):1455-63.

65.       Guo, W., and J.A. Hamilton. 1995. Phase-Behavior and Crystalline-Structures of Cholesteryl Ester Mixtures - a C-13 Masnmr Study. Biophysical Journal 68 (6):2376-86.

66.       Guo, W., and J.A. Hamilton. 1995. Molecular-Organization and Motions of Crystalline Monoacylglycerols and Diacylglycerols - a C-13 Masnmr Study. Biophysical Journal 68 (4):1383-95.

67.       Bhamidipati, S.P., and J.A. Hamilton. 1995. Interactions of Lyso 1-Palmitoylphosphatidylcholine with Phospholipids - a C-13 and P-31 Nmr-Study. Biochemistry 34 (16):5666-77.

68.       Petrou, S., R.W. Ordway, M.T. Kirber, A.M. Dopico, J.A. Hamilton, J.V. Walsh, and J.J. Singer. 1995. Direct Effects of Fatty-Acids and Other Charged Lipids on Ion-Channel Activity in Smooth-Muscle Cells. Prostaglandins Leukotrienes And Essential Fatty Acids 52 (2-3):173-8.

69.       Zhang, F.L., F. Kamp, and J.A. Hamilton. 1996. Dissociation of Long and Very Long Chain Fatty Acids from Phospholipid Bilayers. Biochemistry 35 (50):16055-60.

70.       Guo, W., and J.A. Hamilton. 1996. C-13 Mas Nmr Studies of Crystalline Cholesterol and Lipid Mixtures Modeling Atherosclerotic Plaques. Biophysical Journal 71 (5):2857-68.

71.       Civelek, V.N., J.A. Hamilton, K. Tornheim, K.L. Kelly, and B.E. Corkey. 1996. Intracellular Ph in Adipocytes: Effects of Free Fatty Acid Diffusion across the Plasma Membrane, Lipolytic Agonists, and Insulin. Proceedings Of The National Academy Of Sciences Of The United States Of America 93 (19):10139-44.

72.       Lucke, C., F.L. Zhang, H. Ruterjans, J.A. Hamilton, and J.C. Sacchettini. 1996. Flexibility Is a Likely Determinant of Binding Specificity in the Case of Ileal Lipid Binding Protein. Structure 4 (7):785-800.

73.       Bird, D.A., M. Laposata, and J.A. Hamilton. 1996. Binding of Ethyl Oleate to Low Density Lipoprotein, Phospholipid Vesicles, and Albumin: A C-13 Nmr Study. Journal Of Lipid Research 37 (7):1449-58.

74.       Boyle, E., D.M. Small, D. Gantz, J.A. Hamilton, and J.B. German. 1996. Monoacylglycerols Alter the Lipid Composition and Molecular Mobility of Phosphatidylcholine Bilayers: C-13 Nmr Evidence of Dynamic Lipid Remodeling. Journal Of Lipid Research 37 (4):764-72.

75.       Hamilton, J.A., J.M. Vural, Y.A. Carpentier, and R.J. Deckelbaum. 1996. Incorporation of Medium Chain Triacylglycerols into Phospholipid Bilayers: Effect of Long Chain Triacylglycerols, Cholesterol, and Cholesteryl Esters. Journal Of Lipid Research 37 (4):773-82.

76.       Zhang, F.L., C. Lucke, L.J. Baier, J.C. Sacchettini, and J.A. Hamilton. 1997. Solution Structure of Human Intestinal Fatty Acid Binding Protein: Implications for Ligand Entry and Exit. Journal Of Biomolecular Nmr 9 (3):213-28.

77.       Ek, B.A., D.P. Cistola, J.A. Hamilton, T.L. Kaduce, and A.A. Spector. 1997. Fatty Acid Binding Proteins Reduce 15-Lipoxygenase-Inducedoxygenation of Linoleic Acid and Arachidonic Acid. Biochimica Et Biophysica Acta-Lipids And Lipid Metabolism 1346 (1):75-85.

78.       Shekar, S.C., and J.A. Hamilton. 1997. Separation of a Pair of Interleaved Sideband Families in Magic Angle Spinning Nmr by a Pair of One-Dimensional Experiments. Magnetic Resonance In Chemistry 35 (5):302-5.

79.       Johnson, W.C., M.T. Watkins, J. Hamilton, and D. Baldwin. 1997. Transcutaneous Partial Oxygen Pressure Changes Following Skew Flap and Burgess-Type Below-Knee Amputations. Archives Of Surgery 132 (3):261-3.

80.       Guo, W., J.L. Kirkland, B. Corkey, and J.A. Hamilton. 1998. A C-13 Nuclear Magnetic Resonance Study of Free Fatty Acid Incorporation in Acylated Lipids in Differentiating Preadipocytes. Lipids 33 (5):449-54.

81.       Hamilton, J.A. 1998. Fatty Acid Transport: Difficult or Easy? Journal Of Lipid Research 39 (3):467-81.

82.       Guo, W., J.D. Morrisett, G.M. Lawrie, M.E. Debakey, and J.A. Hamilton. 1998. Identification of Different Lipid Phases and Calcium Phosphate Deposits in Human Carotid Artery Plaques by Mas Nmr Spectroscopy. Magnetic Resonance In Medicine 39 (2):184-9.

83.       Johnson, W.C., M.T. Watkins, D. Baldwin, and J. Hamilton. 1998. Foot Tcpo2 Response to Lumbar Sympathectomy in Patients with Focal Ischemic Necrosis. Annals Of Vascular Surgery 12 (1):70-4.

84.       Hamilton, J.A., and F. Kamp. 1999. How Are Free Fatty Acids Transported in Membranes? Is It by Proteins or by Free Diffusion through the Lipids? Diabetes 48 (12):2255-69.

85.       Guo, W., J.K. Choi, J.L. Kirkland, B.E. Corkey, and J.A. Hamilton. 1999. Incorporation of [1-C-13]Oleate into Cellular Triglycerides in Differentiating 3t3l1 Cells. Lipids 34 (8):825-31.

86.       Hamilton, J.A. 1999. Transport of Fatty Acids across Membranes by the Diffusion Mechanism. Prostaglandins Leukotrienes And Essential Fatty Acids 60 (5-6):291-7.

87.       Lucke, C., D. Fushman, C. Ludwig, J.A. Hamilton, J.C. Sacchettini, and H. Ruterjans. 1999. A Comparative Study of the Backbone Dynamics of Two Closely Related Lipid Binding Proteins: Bovine Heart Fatty Acid Binding Protein and Porcine Ileal Lipid Binding Protein. Molecular And Cellular Biochemistry 192 (1-2):109-21.

88.       Peng, S.Q., W. Guo, J.D. Morrisett, M.T. Johnstone, and J.A. Hamilton. 2000. Quantification of Cholesteryl Esters in Human and Rabbit Atherosclerotic Plaques by Magic-Angle Spinning C-13-Nmr. Arteriosclerosis Thrombosis And Vascular Biology 20 (12):2682-8.

89.       Guo, W., J.D. Morrisett, M.E. Debakey, G.M. Lawrie, and J.A. Hamilton. 2000. Quantification in Situ of Crystalline Cholesterol and Calcium Phosphate Hydroxyapatite in Human Atherosclerotic Plaques by Solid-State Magic Angle Spinning Nmr. Arteriosclerosis Thrombosis And Vascular Biology 20 (6):1630-6.

90.       Lucke, C., F.L. Zhang, J.A. Hamilton, J.C. Sacchettini, and H. Ruterjans. 2000. Solution Structure of Ileal Lipid Binding Protein in Complex with Glycocholate. European Journal Of Biochemistry 267 (10):2929-38.

91.       Johnstone, M.T., R.M. Botnar, A.S. Perez, R. Stewart, W.C. Quist, J.A. Hamilton, and W.J. Manning. 2001. In Vivo Magnetic Resonance Imaging of Experimental Thrombosis in a Rabbit Model. Arteriosclerosis Thrombosis And Vascular Biology 21 (9):1556-60.

92.       Watkins, P.A., J.A. Hamilton, A. Leaf, A.A. Spector, S.A. Moore, R.E. Anderson, H.W. Moser, M.J. Noetzel, and R. Katz. 2001. Brain Uptake and Utilization of Fatty Acids - Applications to Peroxisomal Biogenesis Diseases. Journal Of Molecular Neuroscience 16 (2-3):87-92.

93.       Hamilton, J.A., R.A. Johnson, B. Corkey, and F. Kamp. 2001. Fatty Acid Transport - the Diffusion Mechanism in Model and Biological Membranes. Journal Of Molecular Neuroscience 16 (2-3):99-108.

94.       Katz, R., J.A. Hamilton, A.A. Spector, S.A. Moore, H.W. Moser, M.J. Noetzel, and P.A. Watkins. 2001. Brain Uptake and Utilization of Fatty Acids - Recommendations for Future Research. Journal Of Molecular Neuroscience 16 (2-3):333-5.

95.       Mentzer, B.A.E., F.L. Zhang, and J.A. Hamilton. 2001. Binding of 13-Hode and 15-Hete to Phospholipid Bilayers, Albumin, and Intracellular Fatty Acid Binding Proteins - Implications for Transmembrane and Intracellular Transport and for Protection from Lipid Peroxidation. Journal Of Biological Chemistry 276 (19):15575-80.

96.       Caserta, F., T. Tchkonia, V.N. Civelek, M. Prentki, N.F. Brown, J.D. Mcgarry, R.A. Forse, B.E. Corkey, J.A. Hamilton, and J.L. Kirkland. 2001. Fat Depot Origin Affects Fatty Acid Handling in Cultured Rat and Human Preadipocytes. American Journal Of Physiology-Endocrinology And Metabolism 280 (2):E238-E47.

97.       Yaney, G.C., V.N. Civelek, A.M. Richard, J.S. Dillon, J.T. Deeney, J.A. Hamilton, H.M. Korchak, K. Tornheim, B.E. Corkey, and A.E. Boyd. 2001. Glucagon-Like Peptide 1 Stimulates Lipolysis in Clonal Pancreatic Beta-Cells (Hit). Diabetes 50 (1):56-62.

98.       Hamilton, J.A., W. Guo, and F. Kamp. 2002. Mechanism of Cellular Uptake of Long-Chain Fatty Acids: Do We Need Cellular Proteins? Molecular And Cellular Biochemistry 239 (1-2):17-23.

99.       Hamilton, J.A. 2002. How Fatty Acids Bind to Proteins: The inside Story from Protein Structures. Prostaglandins Leukotrienes And Essential Fatty Acids 67 (2-3):65-72.

100.     Ho, J.K., R.I. Duclos, and J.A. Hamilton. 2002. Interactions of Acyl Carnitines with Model Membranes: A C-13-Nmr Study. Journal Of Lipid Research 43 (9):1429-39.

101.     Finzi, A.C., E.H. Delucia, J.G. Hamilton, D.D. Richter, and W.H. Schlesinger. 2002. The Nitrogen Budget of a Pine Forest under Free Air Co2 Enrichment. Oecologia 132 (4):567-78.

102.     Guo, W., V. Kurze, T. Huber, N.H. Afdhal, K. Beyer, and J.A. Hamilton. 2002. A Solid-State Nmr Study of Phospholipid-Cholesterol Interactions: Sphingomyelin-Cholesterol Binary Systems. Biophysical Journal 83 (3):1465-78.

103.     Choi, J.K., J. Ho, S. Curry, D.H. Qin, R. Bittman, and J.A. Hamilton. 2002. Interactions of Very Long-Chain Saturated Fatty Acids with Serum Albumin. Journal Of Lipid Research 43 (7):1000-10.

104.     Hamilton, J.G., E.H. Delucia, K. George, S.L. Naidu, A.C. Finzi, and W.H. Schlesinger. 2002. Forest Carbon Balance under Elevated Co2. Oecologia 131 (2):250-60.

105.     Kamp, F., N. Kizilbash, B.E. Corkey, P.O. Berggren, and J.A. Hamilton. 2003. Sulfonylureas Rapidly Cross Phospholipid Bilayer Membranes by a Free-Diffusion Mechanism. Diabetes 52 (10):2526-31.

106.     Pownall, H.J., and J.A. Hamilton. 2003. Energy Translocation across Cell Membranes and Membrane Models. Acta Physiologica Scandinavica 178 (4):357-65.

107.     Zhang, F.L., C. Lucke, L.J. Baier, J.C. Sacchettini, and J.A. Hamilton. 2003. 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 42 (24):7339-47.

108.     Han, J.R., J.A. Hamilton, J.L. Kirkland, B.E. Corkey, and W. Guo. 2003. Medium-Chain Oil Reduces Fat Mass and Down-Regulates Expression of Adipogenic Genes in Rats. Obesity Research 11 (6):734-44.

109.     Hamilton, J.A. 2003. Fast Flip-Flop of Cholesterol and Fatty Acids in Membranes: Implications for Membrane Transport Proteins. Current Opinion In Lipidology 14 (3):263-71.

110.     Lucke, C., N. Kizilbash, H.T.B. Van Moerkerk, J.H. Veerkamp, and J.A. Hamilton. 2003. Letter to the Editor: Nmr Assignment and Structural Characterization of the Fatty Acid Binding Protein from the Flight Muscle of Locusta Migratoria. Journal Of Biomolecular Nmr 25 (4):355-6.

111.     Kamp, F., W. Guo, R. Souto, P.F. Pilch, B.E. Corkey, and J.A. Hamilton. 2003. Rapid Flip-Flop of Oleic Acid across the Plasma Membrane of Adipocytes. Journal Of Biological Chemistry 278 (10):7988-95.

112.     Johnson, R.A., J.A. Hamilton, T.S. Worgall, and R.J. Deckelbaum. 2003. Free Fatty Acids Modulate Intermembrane Trafficking of Cholesterol by Increasing Lipid Mobilities: Novel C-13 Nmr Analyses of Free Cholesterol Partitioning. Biochemistry 42 (6):1637-45.

113.     Johnstone, M.T., A.S. Perez, I. Nasser, R. Stewart, A. Vaidya, F. Al Ammary, B. Schmidt, G. Horowitz, J. Dolgoff, J. Hamilton, and W.C. Quist. 2004. Angiotensin Receptor Blockade with Candesartan Attenuates Atherosclerosis, Plaque Disruption, and Macrophage Accumulation within the Plaque in a Rabbit Model. Circulation 110 (14):2060-5.

114.     Hamilton, J.A. 2004. Fatty Acid Interactions with Proteins: What X-Ray Crystal and Nmr Solution Structures Tell Us. Progress In Lipid Research 43 (3):177-99.

115.     Botnar, R.M., A.S. Perez, S. Witte, A.J. Wiethoff, J. Laredo, J. Hamilton, W. Quist, E.C. Parsons, A. Vaidya, A. Kolodziej, J.A. Barrett, P.B. Graham, R.M. Weisskoff, W.J. Manning, and M.T. Johnstone. 2004. In Vivo Molecular Imaging of Acute and Subacute Thrombosis Using a Fibrin-Binding Magnetic Resonance Imaging Contrast Agent. Circulation 109 (16):2023-9.

116.     Lei, T.G., W.S. Xie, J.R. Han, B.E. Corkey, J.A. Hamilton, and W. Guo. 2004. Medium-Chain Fatty Acids Attenuate Agonist-Stimulated Lipolysis, Mimicking the Effects of Starvation. Obesity Research 12 (4):599-611.

117.     Simard, J.R., P.A. Zunszain, C.E. Ha, J.S. Yang, N.V. Bhagavan, I. Petitpas, S. Curry, and J.A. Hamilton. 2005. Locating High-Affinity Fatty Acid-Binding Sites on Albumin by X-Ray Crystallography and Nmr Spectroscopy. Proceedings Of The National Academy Of Sciences Of The United States Of America 102 (50):17958-63.

118.     Guo, W., W.S. Xie, T.G. Lei, and J.A. Hamilton. 2005. Eicosapentaenoic Acid, but Not Oleic Acid, Stimulates Beta-Oxidation in Adipocytes. Lipids 40 (8):815-21.

119.     Viereck, J., F.L. Ruberg, Y. Qiao, A.S. Perez, K. Detwiller, M. Johnstone, and J.A. Hamilton. 2005. Mri of Atherothrombosis Associated with Plaque Rupture. Arteriosclerosis Thrombosis And Vascular Biology 25 (1):240-5.

120.     Lucke, C., D.L. Gantz, E. Klimtchuk, and J.A. Hamilton. 2006. Interactions between Fatty Acids and Alpha-Synuclein. Journal Of Lipid Research 47 (8):1714-24.

121.     Simard, J.R., P.A. Zunszain, J.A. Hamilton, and S. Curry. 2006. Location of High and Low Affinity Fatty Acid Binding Sites on Human Serum Albumin Revealed by Nmr Drug-Competition Analysis. Journal Of Molecular Biology 361 (2):336-51.

122.     Lucke, C., Y. Qiao, H.T.B. Van Moerkerk, J.H. Veerkamp, and J.A. Hamilton. 2006. Fatty-Acid-Binding Protein from the Flight Muscle of Locusta Migratoria: Evolutionary Variations in Fatty Acid Binding. Biochemistry 45 (20):6296-305.

123.     Xie, W., J.A. Hamilton, J.L. Kirkland, B.E. Corkey, and W. Guo. 2006. Oleate-Induced Formation of Fat Cells with Impaired Insulin Sensitivity. Lipids 41 (3):267-71.

124.     Meshulam, T., J.R. Simard, J. Wharton, J.A. Hamilton, and P.F. Pilch. 2006. Role of Caveolin-1 and Cholesterol in Transmembrane Fatty Acid Movement. Biochemistry 45 (9):2882-93.

125.     Guo, W., N. Huang, J. Cai, W.S. Xie, and J.A. Hamilton. 2006. Fatty Acid Transport and Metabolism in Hepg2 Cells. American Journal Of Physiology-Gastrointestinal And Liver Physiology 290 (3):G528-G34.

126.     Ruberg, F.L., J. Viereck, A. Phinikaridou, Y. Qiao, J. Loscalzo, and J.A. Hamilton. 2006. Identification of Cholesteryl Esters in Human Carotid Atherosclerosis by Ex Vivo Image-Guided Proton Mrs. Journal Of Lipid Research 47 (2):310-7.

Curriculum Vitae

Contact Us

James A. Hamilton
Department of Physiology and Biophysics
Boston University School of Medicine
700 Albany Street, W302
Boston MA 02118-2526

Phone:(617) 638-5048
Fax: (617) 638-4041
e-mail:jhamilt@bu.edu