The primary area of study is the identification of protein conformation using chemical cross-linking coupled with mass spectrometric identification of the cross-linked sites. In collaboration with Dr. Sorci-Thomas we are presently working on the configuration of apolipoprotein A-I (apoA-I) on synthetic HDL disks composed of phospholipid and apoA-I. An overall goal is to identify how apoA-I interacts with different enzymes and receptors that are responsible for the conversion of lipid-free apoA-I to spherical HDL and its subsequent uptake and metabolism.  The figure shows our model for lipidated apoA-I disks derived from chemical cross-linking derived constraints.

A second area of active research is the development of mass spectrometric procedures and techniques to detect and quantify phospholipids, gangliosides, HETEs and other bioactive lipids extracted from tissues and cells. We are developing technology to increase the number of lipids that can be quantified from a single analysis and procedures to analyze the large amount of data generated by these procedures.

Our mass spectrometric data are obtained through the Mass Spectrometer Facility that is equipped with a Waters Q-TOF with a mass accuracy of 3 ppm for proteomics.  Lipid analyses (lipidomics) are performed on our new TSQ Quantum and the established Quattro II triple quadrupole mass spectrometers.  A Triversa Nanomate source was recently added to increase sensitivity and analysis accuracy.

Publications:

Thomas, M. J., Bhat, S., and Sorci-Thomas, M. G.: Three-dimensional models of high density lipoprotein apoA-I: Implications for its assembly and function. J. Lipid Res., 49:1875-1883 (2008).

Mulya, A., Lee, J., Gebre, A.M., Thomas, M. J., Colvin, P., Parks, J. S.: Minimally Lipidation of Pre-? HDL by ABCA1 Results in Reduced Ability to Interact with ABCA1. Arterioscler Thromb Vasc Biol., 27:1828-1836 (2007).

Berquin, I. M., Min, Y., Wu, R., Wu, J., Perry, D., Cline, J. M., Thomas, M. J., Thornburg, T., Kulik, G., Smith, A., Edwards, I. J., D’Agostino, R., Zhang, H., Wu, H., Kang, J. X., and Chen, Y. Q.: Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. J. Clin. Invest., 117:1866-1875 (2007).

Bhat, S., Sorci-Thomas, M. G., Tuladhar, R., Samuel, M. P. and Thomas, M. J.: Conformational adaptation of apolipoproteinA-I to discretely sized phospholipid complexes. Biochemistry, 46:7811-7821 (2007).

Zabalawi, M., Bharadwaj, M., Horton, H., Cline, M., Willingham, M., Thomas, M. J., Sorci-Thomas, M. G.: Inflammation and skin cholesterol in LDLr-/-, apoA-I-/- mice: link between cholesterol homeostasis and self-tolerance? J. Lipid Res. 48:52-65 (2006).

Owen, J. S., Bharadwaj, M. S., Thomas, M. J., Bhat, S., Samuel, M. P., Sorci-Thomas, M. G.: Ratio determination of plasma wild-type and mutant apoA-I using mass spectrometry quantification, purification and expression of L159R apoA-I (apoA-IFin). J. Lipid Res., 48:226-234 (2006).

Bleijerveld, O., Houweling, M., Thomas, M. J., and Cui, Z.: Metabolipidomics: profiling metabolism of phospholipid species by stable isotopic precursors and tandem mass spectrometry. Anal. Biochem., 352:1-14 (2006).

Hicks, A. M., DeLong, C. J., Thomas, M. J., Samuel, M., Cui, Z.: Unique molecular signatures of glycerophospholipid species in different rat tissues analyzed by tandem mass spectrometry. Biochim. Biophys. Acta, 1761:1022-1029 (2006).

Tsui, Z-C., Chen, Q-R., Thomas, M. J., Samuel, M., and Cui, Z.: A method for profiling gangliosides in biological samples using electrospray-tandem mass spectrometry.  Anal. Biochem., 341:251-8 (2005).

Bhat, S., Sorci-Thomas, M. G., Samuel, M. P., Alexander, E., Thomas, M. J.: Inter-molecular contact between globular N-terminal fold and C-terminal domain of ApoA-I stabilize its lipid-bound conformation: Studies employing chemical cross-linking and mass spectrometry.  J. Biol. Chem., 280:33015-25 (2005).

Owen, J.S., Wykle, R.L., Samuel, M.P., Thomas, M. .J.: An improved assay for platelet-activating factor using HPLC-tandem mass spectrometry. J. Lipid Res., 46:373-382 (2005).

Schwenke, D. C., Rudel, L. L., Sorci-Thomas, M. G., and Thomas, M. J.: α-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits.  J. Lipid Res. 43:1927-1938 (2002).

Thomas, M. J., Chen, Q., Zabalawi, M., Anderson, R., Weinberg, R., Sorci-Thomas, M. G., and Rudel, L. L.: Is the oxidation of high density lipoprotein lipids different than the oxidation of low density lipoprotein lipids? Biochemistry, 40:1719-1724 (2001).

Thomas, M.J., Thornburg, T., Manning, J., Hooper, K., and Rudel, L.L.: Fatty acid composition of low-density lipoprotein influences its susceptibility to autoxidation. Biochemistry 33:1828-1834 (1994).

Thomas, M. J., and Bielski, B. H. J.: Oxidation and reaction of Trolox c, a tocopherol analogue, in aqueous solution: a pulse radiolysis study. J. Am. Chem. Soc. 111:3315-3319 (1989).

Thomas, M. J., Shirley, P. S., Hedrick, C., and DeChatelet, L. R.: The role of free radical processes in stimulated human polymorphonuclear leukocytes. Biochemistry 25:8042-8048 (1986).

Thomas, M. J., and Foote, C. S.: Chemistry of singlet oxygen. XXVI. Photooxidation of phenols. Photochem. Photobiol. 27:683-693 (1978).

Thomas, M. J., Wagner, P. J., Manion-Schilling, M. L., and Roth, H. D.: Competing triplet and radical pair ¹⁹F nuclear polarization mechanisms in the electron transfer quenching of triplet α,α,α-trifluoroacetophenone. J. Am. Chem. Soc. 99:3843 (1977).

Crandall, J. K., Machleder, W. H., and Thomas, M. J.: Allene epoxidation, isolation of a 1,4-dioxaspiro[2.2]pentane derivative. J. Am. Chem. Soc. 90:7346 (1968).