CURRICULUM VITAE Xianlin Han, Ph.D. Home Address: 427 N. Polo Dr., Clayton MO 63105 Place of Birth: Zhejiang, China Citizenship: United States of America Telephone Numbers: (314) 747-2877 (office) (314) 362-2228 (lab) (314) 230-8479 (home) Email address: xianlin@wustl.edu Present Position: Associate Professor of Medicine Education: 1982 - B.S., Chemistry, Zhejiang University, P.R. China 1985 - M.S., Chemical Thermodynamics, Zhejiang University, P.R. China 1987 - M.A., Physical Chemistry, Washington University, St. Louis, MO 1990 - Ph.D., Biophysical and Bioanalytical Chemistry, Washington University, St. Louis, MO Academic Positions/ Washington University School of Medicine, St. Louis, MO Employment: 2008-present - Associate Professor of Medicine 2000-2008 - Assistant Professor of Medicine 1997-2000 - Research Assistant Professor 1992-1997 - Research Instructor 1990-1992 - Research Associate Honors and Awards: 1986, 1987, 1989, 1990 Fellowship, Washington University, St. Louis, MO 1988 - Tuition Scholarship, Washington University, St. Louis, MO 2003 - Memory Ride Prize Professional Services: 2004-present, Member, Executive Committee, Alzheimer’s Disease Research Center, Washington University School of Medicine 2006-present, Faculty Member of Cardiovascular Trainee Center, Washington University School of Medicine 2007-present, Faculty Member of the Division of Biology and Biomedical Sciences, Washington University School of Medicine 2007-present, Member-at-Large, Chinese American Society for Mass Spectrometry Editorial Responsibilities: Associate Editor: Lipids (2006-present) Section Editor: BBA - Molecular and Cell Biology of Lipids (2008-present) Guest Editor: J. Chromatogr. B (2008-2009) Managing Editor: Front. Biosci. (2006-present) Editorial Board: Am. J. Alz. Dis. Other Dement. (2005-present) J. Lipid Res. (2007-present) Research Proposals (Ad Hoc Reviewer): 2001-present, NIH Study Section (HLBP, NSD-B, ZMH1, ZRG1 MDCN-A (58)R, ZRG1 BST-M (58), ZRG1 IMST-F (30) S, ZDA1 SXC-E (5B)) Alzheimer’s Association Austria National Research Council Singapore Agency for Science, Technology & Research AAAS Research Program Manuscripts for Publication (Ad Hoc Reviewer): Anal. Biochem.; Anal. Chem.; BBA (LIP, MEM); Biochemistry; BMC Bioinformatics; Brain Res.; Electrophoresis; Exp. Eye Res.; Expert Op. Drug Discov.; Expert Rev. Mol. Diagn.; Can. J. Physiol. Pharmacol.; Cell. Mol. Life Sci.; Clin. Chem.; Diabetologia; FEBS Lett.; Int. J. Mass Spectrom.; J. Am. Soc. Mass Spectrom.; J. Chromatogr.; J. Mass Spectrom.; J. Neurochem.; Neurobiol. Aging; Phys. Chem. Lipids; Rapid Commun. Mass Spectrom.; Trends Biotech Professional Societies and Organizations: American Chemical Society American Association for the Advancement of Science American Oil Chemists’ Society The American Society for Biochemistry and Molecular Biology The American Society for Neurochemistry The American Society for Mass Spectrometry International Society for Mass Spectrometry The Society for Neuroscience Ongoing Research Support: R01AG023168 X. Han (PI) 4/15/05-3/31/10 3.60 Cal. Months National Institute on Aging $184,500 The Role of Sulfatides in Alzheimer’s Disease The major goals of this project are to identify the role of sulfatides in the interactions between apolipoprotein E, amyloid peptides and sulfatides and to identify the molecular mechanisms leading to the amyloid deposition and sulfatide depletion at the very early stage of Alzheimer’s disease. R01AG031675 X. Han (PI) 9/1/07-7/31/12 3.0 Cal. Months National Institute on Aging $348,610 Shotgun Lipidomics and Alterations in Sphingolipidomes in Alzheimer’s Diseases The goals of this project are to develop an enhanced shotgun lipidomics approach for the analyses of many low abundance lipid classes in the sphingolipidome and other related lipid classes, develop our current data processing program for shotgun lipidomics into an automated, high-throughput bioinformatics approach, identify the biochemical mechanism(s) underlying the altered sphingolipid pathways and/or sphingolipidome networks present in very mild AD and identify novel lipid biomarker(s) from CSF lipid extracts for the early diagnosis of AD. 1R01NS054008-01A2 (Subcontract PI, X. Han) R. Kaddurah-Daouk 10/01/07-09/30/10 0.08 Cal. Months National Institutes of Health $35,000 Metabolic Signatures for Alzheimer’s Disease The goal of this project is to determine alterations in plasmalogen content in post-mortem brain samples from subjects with AD and correlate the alterations with the neurotransmitter release. 2PO1HL57278-11A1 PPG Project 2, X. Han (PI) 08/1/08-07/31/13 3.0 Cal. Months NIH/NHLBI $237,526 Membrane-Mediated Alterations in Diabetes. Project 2: Altered Cardiolipin Metabolism and Mitochondrial Dysfunction in Diabetic Hearts The major goals of this project are to identify the role of increased myocardial fatty acid substrate utilization in the diabetic state in promoting accelerated CL remodeling and deficiencies in CL biosynthesis; to determine the resultant mitochondrial dysfunction and altered signaling arising from the altered CL profile; and to examine the role of the altered CL profile in mediating cellular apoptosis. 2PO1HL57278-11A1 PPG Core A, X. Han (Director) 08/1/08-07/31/13 NIH/NHLBI $212,764 1.8 Cal. Months Membrane-Mediated Alterations in Diabetes. Core A: Chemistry The major goal of this core is to provide cost effective instrumental expertise for the analytical and synthetic methodologies which include: shotgun lipidomics analyses of lipids; proteomics analyses of targeted proteins overexpressed in genetically engineered mice that are related to lipid metabolic alterations in diabetic cardiomyopathy; targeted metabolomic analyses of mitochondrial function using MALDI-TOF/TOF MS; and synthetic expertise for determination of the chemical mechanisms contributing to diabetic cardiomyopathy. Finished Research Projects (Last three years): PO1HL57278 PPG Project 3, J. Turk (PI) 4/1/02-3/31/07 NIH/NHLBI Membrane-Mediated Alterations in Diabetes. The major goals of this project were to identify the role of altered peroxisomal lipid metabolism and intracellular phospholipase A2 activities in contributing to monocyte migration, lipid second messenger generation and lipid accumulation. Role: Co-Investigator PO1HL57278 PPG Core A, X. Han (PI, Director) 4/1/02-8/15/08 3.0 Cal. Months NIH/NHLBI $232,700 Membrane-mediated Alterations in Diabetes: Core A (Chemistry and Bioanalytical Chemistry) The major goal of this core is to provide cost effective instrumental expertise for the analytical and synthetic methodologies which include: 1) analyses of polar and neutral lipids using ESI/MS and ELSD with sensitivity at the subpicomole to picomole range; 2) protein sequencing and protein posttranslational modification determination utilizing LC/MS (proteomics); 3) the synthesis of phospholipase A2 inhibitor and its resolved enantiomers; 4) real-time phospholipase A2 assays; 5) quantitative PCR utilizing Taqman methodology. P01AG0399121 Project 2, D.M. Holtzman (PI) 7/1/04-12/31/08 0.48 Cal. Months National Institute on Aging $101,436 Healthy Aging and Senile Dementia The major goals of this project are to develop and/or improve new biomarkers that will assist in both predicting development and progression of AD as well as improving early diagnosis. Role: Co-Investigator P20 Initiative D. Ory (PI) 08/15/05-08/14/07 NIH/Washington University Plasma Oxysterols as Biomarkers for Atherosclerosis The major goals of this project are to identify whether plasma oxysterols can serve as novel biomarkers for detection of coronary heart disease. Role: Co-Investigator P20 Initiative R.W. Gross (PI) 08/15/05-08/14/07 NIH/Washington University Mass Spectrometric Identification of Biomarkers in Diabetic Cardiomyopathy The major goals of this project were to identify alterations in serum lipid profiles as novel biomarkers for detection of diabetic cardiomyopathy. Role: Co-Investigator Students/Fellows Training Record: Trainees Carol O’Hear, 2000-2003, B.S. Xiong Su, 1999-2004, Ph.D. Jingyue Yang, 1999-2004, Ph.D. Wei Yan, 2000-2005, Ph.D. Sung Ho Moon, 2000-2006, Ph.D. Yunhua Zhou, 2007, Visiting scholar Rebecca Miller, 2008-present, Post-doctoral fellow Michael Kiebish, 2008-present, Post-doctoral fellow Hui Jiang, 2009-present, Post-doctoral fellow Xiaoling Fang, 2009-present, Post-doctoral fellow Graduate Thesis Committees Yin Li (M. Gross, Chemistry, Washington University, 2006) Libia Saborido Basconcillo (B.E. McCarry, Chemistry, McMaster University, Canada, 2008) Jacqui Hawkins (M. Sands, Genetics, Washington University, 2008-present) Peer Reviewed Research Publications: 1. Lin, R., Han, X., and Yan, W. (1988) Vapor-flow calorimeter-determination of heats of vaporization and vapor heat capacities of benzene. Huaxue Xuebao 46, 746-750. 2. Han, X. and Gross, R.W. (1990) Plasmenylcholine and phosphatidylcholine membrane bilayer possess distinct conformational motifs. Biochemistry 29, 4992-4996. 3. Han, X. and Gross, R.W. (1991) Proton nuclear magnetic resonance studies on the molecular dynamics of plasmenylcholine/cholesterol and phosphatidylcholine/cholesterol bilayers. Biochim. Biophys. Acta 1063, 129-136. 4. Han, X. and Gross, R.W. (1991) Alterations in membrane dynamics elicited by amphiphilic compounds are augmented in plasmenylcholine bilayers. Biochim. Biophys. Acta 1069, 37-45. 5. Han, X., Chen, X., and Gross, R.W. (1991) Chemical and magnetic inequivalence of glycerol protons in Individual Subclasses of Choline Glycerophospholipids: Implications for SubclassSpecific Changes in Membrane Conformational States. J. Am. Chem. Soc. 113, 7104-7109. 6. Han, X., Zupan, L.A., Hazen, S.L., and Gross, R.W. (1992) Semisynthesis and purification of homogeneous plasmenylcholine molecular species. Anal. Biochem. 200, 119-124. 7. Pak, J.H., Han, X., and Gross, R.W. (1992) Differential molecular dynamics and transmembrane fluidity gradients in canine myocardial sarcolemma and sarcoplasmic reticulum. Chem. Phys. Lipids 61, 111-119. 8. Han, X. and Gross, R.W. (1992) Non-monotonic alterations in the fluorescence anisotropy of polar head group labeled fluorophores during the L-Hii phase transition of phospholipids. Biophys. J. 63, 309-316. 9. Gross, R.W., Ramanadham, S., Kruszka, K.K., Han, X., and Turk, J. (1993) Rat and human pancreatic islet cells contain a calcium ion independent phospholipase A2 activity selective for hydrolysis of arachidonate which is stimulated by adenosine triphosphate and is specifically localized to islet -cells. Biochemistry 32, 327-336 10. Ramanadham, S., Gross, R.W., Han, X., and Turk, J. (1993) Inhibition of arachidonate release by secretagogue-stimulated pancreatic islets suppresses both insulin secretion and the rise in ßCell cytosolic calcium ion concentration. Biochemistry 32, 337-346. 11. Chen, X., Han, X., and Gross, R.W. (1993) Dynamics of binary mixtures of plasmenylcholine /arachidonic acid and phosphatidylcholine/arachidonic acid - a study using fluorescence and NMR spectroscopy. Biochim. Biophys. Acta 1149, 241-248. 12. Han, X. and Gross, R.W. (1994) Electrospray ionization mass spectroscopic analysis of human erythrocyte plasma membrane phospholipids. Proc. Natl. Acad. Sci. USA 91, 10635-10639. 13. Wang, K., Han, X., Gross, R.W., and Gokel, G.W. (1995) The first evidence for triple cation binding by multi-ring macrocyclic polyethers: An electrospray ionization mass spectral study. J. Chem. Soc., Chem. Commun. 641-642. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. Han, X. and Gross, R.W. (1995) Structural analysis of picomole amounts of phospholipids utilizing electrospray ionization tandem mass spectrometry. J. Am. Soc. Mass Specotrom. 6, 1202-1210. Wang, K., Han, X., Gross, R.W., and Gokel, G.W. (1995) Direct evidence for arymethyl ether coordination of sodium and potassium cations: an electrospray ionization mass spectrometry study. J. Am. Chem. Soc. 117, 7680-7686. Han, X. and Gross, R.W. (1996) Structural determination of lysophospholipid regioisomers by electrospray ionization tandem mass spectroscopy. J. Am. Chem. Soc. 118, 451-457. Han, X., Gubitosi-Klug, R.A., Collins, B., and Gross, R.W. (1996) Alternations in individual molecular species of human platelet phospholipids during thrombin stimulation: Electrospray ionization mass spectrometry-facilitated identification of the boundary conditions for the magnitude and selectivity of thrombin-induced platelet phospholipid hydrolysis. Biochemistry 35, 5822-5832. Ford, D.A., Han, X., Horner, C.C., and Gross, R.W. (1996) Accumulation of unsaturated acylcarnitine molecular species during acute myocardial ischemia: Metabolic compartmentalization of products of fatty acyl chain elogation in the acylcarnitine pool. Biochemistry 35, 7903-7909. Kwon, G., Bohrer, A., Han, X., Corbett, J.A., Ma, Zh., Gross, R.W., McDaniel, M.L, and Turk, J. (1996) Characterization of the sphingomyelin content of isolated pancreatic islets. Evaluation of the role of sphingomyelin hydrolysis in the action of interleukin-1 to induce islet overproduction of nitric oxide. Biochim. Biophys. Acta 1300, 63-72. Zeng, Y., Han, X., and Gross, R.W. (1998) Phospholipid subclass specific alterations in the passive ion permeability of membrane bilayers: Separation of enthalpic and entropic contributions to transbilayer ion flux. Biochemistry 37, 2346-2355. Zeng, Y., Han, X., Schlesinger, P., and Gross, R.W. (1998) Nonesterified fatty acids induce transmembrane monovalent cation flux: Host-guest interactions as determinants of fatty acidinduced ion transport. Biochemistry 37, 9497-9508. Han, X., Ramanadham, S., Turk, J., and Gross, R.W. (1998) Reconstitution of membrane fusion between pancreatic islet secretory granules and plasma membranes: Catalysis by a protein constituent recognized by monoclonal antibodies directed against glyceraldehyde-3phosphate dehydrogenase. Biochim. Biophys. Acta 1414, 95-107. Zeng, Y., Han, X., and Gross, R.W. (1999) Phospholipid subclass-specific partitioning of lipophilic ions in membrane-water systems. Biochem. J. 338, 651-658. Han, X., Abendschein, A.R., Kelley, J.G., and Gross, R.W. (2000) Diabetes-induced changes in specific lipid molecular species in rat myocardium. Biochem. J. 352, 79-89. Han, X., Holtzman, D.M., and McKeel Jr, D. (2001) Plasmalogen deficiency in early Alzheimer’s disease subjects and in animal models: Molecular characterization using electrospray ionization mass spectrometry. J. Neurochem. 77, 1168-1180. Han, X. and Gross, R.W. (2001) Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from biological samples by electrospray ionization tandem mass spectrometry Anal. Biochem. 298, 88-100. DeMattos, R.B., Brendza, R., Heuser, J., Kierson, M., Fryer, J., Fagan, A.M., Han, X., and Holtzman, D.M. (2001) Purification and characterization of astrocyte-secreted apolipoprotein E and J containing lipoproteins from wild-type and human apoE transgenic mice. Neurochem. Int. 39, 415-425. Finck, B.N., Lehman, J.J., Leone, T.C., Welch, M.J., Bennett, M.J., Kovacs, A., Han, X., Gross, R.W., Kozak, R., Lopaschuk, G.D., and Kelly, D.P. (2002) The cardiac phenotype induced by PPAR overexpression mimics that caused by diabetes mellitus. J. Clin. Invest. 109, 121-130. Han, X. (2002) Characterization and direct quantitation of ceramide molecular species from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal. Biochem. 302, 199-212. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. Pike, L.J., Han, X., Chung, K.-N., Gross, R.W. (2002) Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their composition is independent of caveolin-1 expression: A quantitative electrospray ionization/mass spectrometric analysis. Biochemistry 41, 2075-2088. Han, X., Holtzman, D.M., McKeel Jr., D.W., Kelley, J., and Morris, J.C. (2002) Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer’s disease: potential role in disease pathogenesis. J. Neurochem. 82, 809-818. Jenkins, C.M., Han, X., Mancuso, D.J., and Gross, R.W. (2002) Identification of iPLA2, and not iPLA2, as the mediator of AVP-induced arachidonic acid release in A-10 smooth muscle cells: Enantioselective mechanism-based discrimination of mammalian iPLA2s. J. Biol. Chem. 277, 32807-32814. Glaser, P.E., Han, X., and Gross, R.W. (2002) Tubulin is the endogenous inhibitor of glyceraldehyde 3-phosphate dehydrogenase isoform that catalyzes membrane fusion: Implications for the coordinated regulation of glycolysis and membrane fusion. Proc. Natl. Acad. Sci. USA 99, 14104-14109. Narita, M., Holtzman, D.M., Fagan, A.M., LaDu, M.J., Yu, L., Han, X., Gross, R. W., Bu, G., and Schwartz, A.L. (2002) Cellular catabolism of lipid poor apolipoprotein E via cell surface LDL receptor-related protein. J. Biochem. 132, 743-749. Finck, B.N., Han, X., Courtois, M., Aimond, F., Nerbonne, J.M., Kovacs, A., Gross, R.W., and Kelly, D.A. (2003) A critical role for PPAR-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation of phenotype by dietary fat content. Proc. Natl. Acad. Sci. USA 100, 1226-1231. Han, X., Cheng, H., Fryer, J. D., Fagan, A. M., and Holtzman, D.M. (2003) Novel role for apolipoprotein E in the central nervous system: Modulation of sulfatide content. J. Biol. Chem. 278, 8043-8051. Acharya, U., Patel, S., Koundakjian, E., Nagashima, K., Han, X., and Acharya, J.K. (2003) Modulation of sphingolipid biosynthetic pathway rescues photoreceptor degeneration. Science 299, 1740-1743. Listenberger, L.L., Han, X., Lewis, S.E., Cases, S., Farese, Jr., R.V., Ory, D.S., and Schaffer, J.E. (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl. Acad. Sci. USA 100, 3077-3082. Mancuso, D.J., Abendschein, D.R., Jenkins, C.M., Han, X., Saffitz, J.E., Schuessler, R.B., Gross, R.W. (2003) Cardiac ischemia activates calcium-independent phospholipase A2 precipitating ventricular tachyarrhythmias in transgenic mice: Rescue of the lethal electrophysiologic phenotype by mechanism-based inhibition. J. Biol. Chem. 278, 2223122236. Yang, J., Han, X., and Gross, R.W. (2003) Identification of hepatic peroxisomal phospholipase A2 and characterization of arachidonic acid-containing choline glycerophospholipids in hepatic peroxisomes. FEBS Lett. 546, 247-250. Han, X., Fagan, A.M., Morris, J. C., Xiong, C., and Holtzman, D.M. (2003) CSF sulfatide is decreased in individuals with mild cognitive impairment/very mild dementia. Ann. Neurol. 54, 115-119. Cheng, H., Xu, J., McKeel Jr., D.W., and Han, X. (2003) Specificity and potential mechanism of sulfatide deficiency in Alzheimer’s disease: An electrospray ionization mass spectrometric study. Cell. Mol. Biol. 49, 809-818. Jenkins, C.M., Han, X., Yang, J., Mancuso, D.J., Sims, H.F., Muslin, A.J., and Gross, R.W. (2003) Purification of recombinant human cPLA2 and identification of C-terminal farnesylation, proteolytic processing, and carboxymethylation by MALDI-TOF-TOF analysis. Biochemistry 42, 11798-11807. Newberry, E.P., Xie, Y., Kennedy, S., Han, X., Buhman, K.K., Luo, J., Gross, R.W., and Davidson, N.O. (2003) Decreased hepatic triglyceride accumulation and altered fatty acid 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. uptake in mice with deletion of the liver fatty acid-binding protein gene. J. Biol. Chem. 278, 51664-51672. Lee, J.-T., Xu, J., Lee, J.-M., Ku, G., Han, X., Yang, D.-I., Chen, S., and Hsu, C.-Y. (2004) Amyloid beta peptides induce oligodendrocyte death by activating neutral sphingomyelinaseceramide pathway. J. Cell. Biol. 164, 123-131. Su, X., Han, X., Yang, J., Mancuso, D.J., Chen, J., Bickel, P.B., and Gross, R.W. (2004) Sequential ordered fatty acid oxidation and 9 desaturation are major determinants of lipids storage and utilization in differentiating adipocytes. Biochemistry 43, 5033-5044. Han, X., Yang, J., Cheng, H., Ye, H., and Gross, R.W. (2004) Towards fingerprinting cellular lipidomes directly from biological samples by two-dimensional electrospray ionization mass spectrometry. Anal. Biochem. 330, 317-331. Wahrle, S.E., Jiang, H., Parsadanian, M., Legleiter, J., Han, X., Fryer, J.D., Kowalewski, T., and Holtzman, D.M. (2004) ABCA1 is required for normal CNS apoE levels and for lipidation of astrocyte-secreted apoE. J. Biol. Chem. 279, 40987-40993. Han, X., Cheng, H., Mancuso, D., and Gross, R.W. (2004) Caloric restriction results in phospholipid depletion, membrane remodeling and triacylglycerol accumulation in murine myocardium. Biochemistry 43,15584-15594. Han, X. and Cheng, H. (2005) Characterization and direct quantitation of cerebroside molecular species from lipid extracts by shotgun lipidomics. J. Lipid Res. 46, 163-175. Chiu, H.-C., Kovacs, A., Blanton, R.M., Han, X., Courtois, M., Weinheimer, C.J., Yamada, K.A., Brunet, S., Xu, H., Nerbonne, J.M., Welch, M.J., Kim, J., Sharpe, T., Gropler, R.J., Herrero, P., Ory, D.S., and Schaffer, J.E. (2005) Transgenic expression of FATP1 in the heart causes lipotoxic cardiomyopathy. Circ. Res. 96, 225-233. Su, X., Han, X., Mancuso, D.J., Abendschein, D.R., and Gross, R.W. (2005) Accumulation of long chain acylcarnitine and 3-hydroxy acylcarnitine molecular species in diabetic myocardium: Identification of alterations in mitochondrial fatty acid processing in diabetic myocardium by shotgun lipidomics. Biochemistry 44, 5234-5245. Han, X., Yang, K., Cheng, H., Fikes, K., and Gross, R.W. (2005) Shotgun lipidomics of phosphoethanolamine-containing lipid molecular species in biological samples after one-step in situ derivatization. J. Lipid Res. 46, 1548-1560. Yan, W., Jenkins, C.M., Han, X., Mancuso, D.J., Sims, H.F., Yang, K., and Gross, R.W. (2005) The highly selective production of 2-arachidonoyl lysophosphatidylcholine catalyzed by purified calcium-independent phospholipase A2 (iPLA2): Identification of a novel enzymatic mediator for the generation of a key branch point intermediate in eicosanoid signaling. J. Biol. Chem. 280, 26669 - 26679. Pike, L.J., Han, X., and Gross, R.W. (2005) EGF receptors are localized to lipid rafts that contain a balance of inner and outer leaflet lipids: A shotgun lipidomics study. J. Biol. Chem. 280, 26796-26804. Yang, J., Gibson, B., Snider, J., Jenkins, C.M., Han, X., and Gross, R.W. (2005) Submicromolar concentrations of palmitoyl-CoA specifically thioesterify cysteine 244 in glyceraldehyde-3-phosphate dehydrogenase inhibiting enzyme activity: A novel mechanism potentially underlying fatty acid induced insulin resistance. Biochemistry 44, 11903-11912. Han, X., Yang, J., Cheng, H., Yang, K., Abendschein, D.R., and Gross, R.W. (2005) Shotgun lipidomics identifies cardiolipin depletion in diabetic myocardium linking altered substrate utilization with mitochondrial dysfunction. Biochemistry 44, 16684-16694. Han, X., Yang, K., Yang, J., Fikes, K.N., Cheng, H., and Gross, R.W. (2006) Factors influencing the electrospray intrasource separation and selective ionization of glycerophospholipids. J. Am. Soc. Mass Spectrom. 17, 264-274. Han, X., Yang, K., Yang, J., Cheng, H., and Gross, R.W. (2006) Shotgun lipidomics of cardiolipin molecular species in lipid extracts of biological samples. J. Lipid Res. 47, 864-879. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. Gale, S.E., Frolov, A., Han, X., Bickel, P.E., Cao, L., Bowcock, A., Schaffer, J.E., and Ory, D.S. (2006) A regulatory role for AGPAT2 in adipocyte differentiation. J. Biol. Chem. 281, 11082-11089. Cheng, H., Guan, S., and Han, X. (2006) Abundance of triacylglycerols in ganglia and their depletion in diabetic mice: Implications for the role of altered triacylglycerols in diabetic neuropathy. J. Neurochem. 97, 1288-1300. Jiang, X. and Han, X. (2006) Characterization and direct quantitation of sphingoid base-1phosphates from lipid extracts: A shotgun lipidomics approach. J. Lipid Res. 47, 1865-1873. Hiraoka, M., Abe, A., Lu, Y., Yang, K., Han, X., Gross, R.W., and Shayman, J.A. (2006) Lysosomal phospholipase A2 and phospholipidosis. Mol. Cell. Biol. 26, 6139-6148. Fox, T.E., Han, X., Merrill, A.H. Jr, Martin, R.E., Anderson, R.E., Thomas W Gardner, T.W., and Kester, M. (2006) Diabetes alters sphingolipid metabolism in the retina: A potential mechanism of cell death in diabetic retinopathy. Diabetes 55, 3573-3580. Borradaile, N.M., Han, X., Harp, J.D., Ory, D.S., Schaffer, J.E. (2006) Disruption of endoplasmic reticulum structure and integrity is central to lipotoxic cell death. J. Lipid Res. 47, 2726-2737. Jiang, X., Ory, D.S., and Han, X. (2007) Characterization of oxysterols by electrospray ionization tandem mass spectrometry after one-step derivatization with dimethylglycine. Rapid Commun. Mass Spectrom. 21, 141-152. Cheng, H., Jiang, X. and Han, X. (2007) Alterations in lipid homeostasis of mouse dorsal root ganglia induced by apolipoprotein E deficiency: A shotgun lipidomics study. J. Neurochem. 101, 57-76. Mancuso, D.J., Han, X., Jenkins, C.M., Lehman, J.J., Sambandam, N., Sims, H.F., Yang, J., Yan, W., Yang, K., Green, K., Abendschein, D.R., Saffitz, J.E., and Gross, R.W. (2007) Dramatic accumulation of triglycerides and precipitation of cardiac dysfunction during brief caloric restriction in myocardium expressing calcium-independent phospholipase A2. J. Biol. Chem. 282, 9216-9227. Yang, J., Sambandam, N., Han, X., Gross, R.W., Courtois, M., Kovacs, A., Febbraio, M., Finck, B.N., and Kelly, D.P. (2007) CD36 deficiency rescues lipotoxic cardiomyopathy. Circ. Res., 100, 1208-1217. Morishima-Kawashima, M., Han, X., Tanimura, Y., Hamanaka, H., Kobayashi, M., Sakurai, T., Yokoyama, M., Wada, K., Nukina, N., Fujita, S.C., and Ihara, Y. (2007) Effects of human apolipoprotein E isoforms on the amyloid -protein concentration and lipid composition in brain low-density membrane domains. J. Neurochem. 101, 949-958. Han, X., Yang, J., Yang, K., Zhao, Z., Abendschein, D.R., and Gross, R.W. (2007) Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: A shotgun lipidomics study. Biochemistry 46, 6417-6428. Nassir, F., Wilson, B., Han, X., Gross, R.W., and Abumrad, N.A. (2007) CD36 facilitates fatty acid and cholesterol uptake by the proximal intestine. J. Biol. Chem. 19493-19501. Sun, G., Yang, K., Zhao, Z., Guan, S., Han, X., and Gross, R.W. (2007) A shotgun metabolomics approach for rapid analysis of negatively-charged water-soluble cellular metabolites from mouse heart tissue. Anal. Chem. 79, 6629-6640. Chen, C.-L., Liu, I-H., Fliesler, S.J., Han, X., Huang, S.S., and Huang, J.S. (2007) Cholesterol suppresses cellular TGF-beta responsiveness: Implications in atherogenesis. J. Cell Sci. 120, 3059-3521. Jiang, X., Cheng, H., Yang, K., Gross, R.W. and Han, X. (2007) Alkaline methanolysis of lipid extracts extends shotgun lipidomics analyses to the low abundance regime of cellular sphingolipids. Anal. Biochem. 371, 135-145. Mancuso, D.J., Sims, H.F., Han, X., Jenkins, C.M., Guan, S., Yang, K., Moon, S.H., Abumrad, N., Schlesinger, P., and Gross, R.W. (2007) Genetic ablation of calcium-independent 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. phospholipase A2 leads to alterations in mitochondrial lipid metabolism and function resulting in a mitochondrial bioenergetic deficient phenotype. J. Biol. Chem. 282, 34611-34622. Burkart, E.M., Sambandam, N., Han, X., Gross, R.W., Courtois, M., Shoghi, K., Welch, M.J., Kelly, D.P. (2007) The nuclear receptors PPAR/ and PPAR direct distinct cardiac metabolic regulatory programs. J. Clin. Invest. 117, 3930-3939. Yang, K., Zhao, Z., Gross, R.W., and Han, X. (2007) Shotgun lipidomics identifies a paired rule for the presence of isomeric ether phospholipid molecular species. PLoS ONE 2(12), e1368. Zeng, Y., Cheng, H., Jiang, X., and Han X. (2008) Endosomes and lysosomes play distinct roles in sulfatide-induced neuroblastoma apoptosis: Potential mechanisms contributing to abnormal sulfatide metabolism in related neuronal diseases. Biochem. J. 410, 81-92. Han, X., Yang, K., and Gross, R.W. (2008) Microfluidics-based electrospray ionization enhances intrasource separation of lipid classes and extends identification of individual molecular species through multi-dimensional mass spectrometry: Development of an automated high throughput platform for shotgun lipidomics. Rapid Commun. Mass Spectrom. 22, 2115-2124. PMID: 18523984. Cheng, H., Mancuso, D.J., Jiang, X., Guan, S., Yang, J., Yang, K., Sun, G., Gross, R.W. and Han, X. (2008) Shotgun lipidomics reveals the temporally dependent, highly diversified cardiolipin profile in the mammalian brain: Coordinated postnatal diversification of cardiolipin molecular species with neuronal remodeling Biochemistry 47, 5869-5880, PMID: 18454555. Ye, H., Hill, J., Kauffman, J., Gryniewicz, C., and Han, X. (2008) Detection of protein modifications and counterfeit protein pharmaceuticals using iTRAQ and MALDI TOF/TOF mass spectrometry: Studies with insulins. Anal. Biochem. 379, 182-191, PMID: 18489896. Kiebish, M.A., Han, X., Cheng, H., Lunceford, A., Clarke, C.F., and Seyfried, T.N. (2008) Lipidomic analysis and electron transport chain activities in the C57BL/6J mouse brain mitochondria. J. Neurochem. 106, 299-312, PMID: 18373617. Zeng, Y. and Han, X. (2008) Sulfatides facilitate apolipoprotein E-mediated amyloid- peptide degradation through an endocytotic pathway. J. Neurochem. 106, 1275-1286, PMID: 18485101. Lehman, J.J., Boudina, S., Banke, N.H., Sambandam, N., Han, X., Young, D.M., Leone, T.C., Gross, R.W., Lewandowski, E.D., Abel, E.D., and Kelly, D.P. (2008) The transcriptional coactivator PGC-1 is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis. Am. J. Physiol., 295, H185-H196. PMID: 18487436. Sun, Y., Witte, D.P., Ran, H., Zamzow, M., Barnes, S., Cheng, H., Han, X., Williams, M.T., Skelton, M.R., Vorhees, C.V., and Grabowski, G.A. (2008) Neurological deficits and glycosphingolipid accumulation in Saposin B deficient mice. Hum. Mol. Genet. 17, 2345-2356. PMID: 18480170. Maysinger, D., Holmes, M., Epand, R.M., Han, X., Holtzman, D., Pertens, E., Barlas, C., Foerster, A., Diamond, J. (2008) Ceramide is responsible for the failure of compensatory nerve sprouting in apoE KO mice. J. Neurosci. 28, 7891-7899. Kilkus, J., Goswami, R., Dawson, S. A., Testai, F. D., Berdyshev, E., Han, X., and Dawson, G. (2008) Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons. J. Neurochem. 106, 1745-1757. Kiebish, M.A., Han, X., Cheng, H., Chuang, J.H., and Seyfried, T.N. (2008) Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas. Lipids, 43 951959. Sun, G., Yang, K., Zhao, Z., Guan, S., Han, X., and Gross, R.W. (2008) Matrix-assisted laser desorption/ionization-time of flight mass spectrometric analysis of cellular glycerophospholipids enabled by multiplexed solvent dependent analyte-matrix interactions. Anal. Chem. 80, 7576-7585. 91. Kiebish, M.A., Han, X., Cheng, H., Chuang, J.H., and Seyfried, T.N. (2008) Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: Lipidomic evidence supporting the Warburg theory of cancer. J. Lipid Res. 49, 2545-2556. 92. Jiang, X., Yang, K., and Han, X. (2009) Direct quantitation of psychosine from alkaline-treated lipid extracts with a semi-synthetic internal standard. J. Lipid Res. 50, 162–172. 93. Gale, S.E., Westover, E.J., Dudley, N., Krishnan, K., Merlin, S., Scherrer, D.E., Han, X., Zhai, X., Brockman, H.L., Brown, R.E., Covey, D.E., Schaffer, J.E., Schlesinger, P., Ory, D.S. (2009) Side-chain oxygenated cholesterol regulates cellular cholesterol homeostasis through direct sterol-membrane interactions. J. Biol. Chem. 284, 1755-1764. 94. Vempati, U. D., Han, X., and Moraes, C. T. (2009) Lack of cytochrome c in mouse fibroblasts disrupts assembly/stability of respiratory complexes I and IV. J. Biol. Chem. 284, 4383-4391. 95. Gropler, M.C., Harris, T.E., Hall, A.M., Wolins, N.E., Gross, R.W., Han, X., Chen, Z., and Finck, B.N. (2009) Lipin 2 is a liver-enriched phosphatidate phosphohydrolase enzyme that is dynamically regulated by fasting and obesity in mice. J. Biol. Chem., 284, 6763-6772. 96. Yang, K., Cheng, H., Gross, R.W., and Han, X. (2009) Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics. Anal. Chem. 81, 4356-4368. 97. Kiebish, M.A., Han, X., Cheng, H., and Seyfried, T.N. (2009) In vitro growth environment produces lipidomic and electron transport chain abnormalities in mitochondria from nontumorigenic astrocytes and brain tumors. ASN NEURO, 1, e00011. doi:10.1042/AN20090011. 98. Yang, K., Zhao, Z, Gross, R.W., and Han, X. (2009) Systematic analysis of choline-containing phospholipids using multi-dimensional mass spectrometry-based shotgun lipidomics. J. Chromatogr. B, 877, 2924–2936. 99. Cheng, H., Zhou, Y., Holtzman, D.M., and Han, X. (2009) Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer’s disease. Neurobiol. Aging. doi:10.1016/j.neurobiolaging.2008.07.020. 100. Saadat, L., Dupree, J.L., Kilkus, J., Han, X., Traka, M., Proia, R.L., Dawson, G., and Popko, B. (2009) Absence of oligodendroglial glocusylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice. Glia doi: 10.1002/glia.20930. Invited Review Papers: 1. Han, X. and Gross, R. W. (2003) Global analyses of cellular lipidomes directly from crude extracts of biological samples by electrospray ionization mass spectrometry: A bridge to lipidomics. J. Lipid Res. 44, 1071-1079. 2. Han, X. (2004) The role of apolipoprotein E in lipid metabolism in the central nervous system. Cell. Mol. Life Sci. 61, 1896-1906. 3. Han, X. (2004) Sulfatide content is specifically depleted in subjects with very mild Alzheimer’s dementia. Dementia Japan 18, 73-79. 4. Han, X. (2005) Lipid alterations in the earliest clinical stage of Alzheimer’s disease: Implication of the role of lipids in the pathogenesis of Alzheimer’s disease. Curr. Alz. Res. 2, 65-77. 5. Han, X. and Gross, R.W. (2005) Shotgun lipidomics: Electrospray ionization mass spectrometric analysis and quantitation of the cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom. Rev. 24, 367-412. 6. Han, X. and Gross, R.W. (2005) Shotgun lipidomics: multi-dimensional mass spectrometric analysis of cellular lipidomes. Expert Rev. Proteomics 2, 253-264. 7. Gross, R.W., Jenkins, C.M., Yang, J., Mancuso, D.J., and Han, X. (2005) Functional lipidomics: The roles of specialized lipids and lipid-protein interactions in modulating neuronal function. Prostag. Oth. Lipid M. 77, 52-64. 8. Gross, R.W. and Han, X. (2006) Unlocking the complexity of lipids: Using lipidomics to identify disease mechanisms, biomarkers, and treatment efficacy. Future Lipidol. 1, 539-547. 9. Han, X. (2007) Neurolipidomics: challenges and developments. Front. Biosci. 12, 2601-2615. 10. Han, X. (2007) An update in lipidomics: Progress and application in biomarker and drug development. Curr. Opin. Mol. Ther. 9, 586-591. 11. Gross, R.W. and Han, X. (2007) Lipidomics in diabetes and the metabolic syndrome. Methods Enz. 433C, 73-90. 12. Han, X. (2007) Potential mechanisms contributing to sulfatide depletion at the earliest clinically recognizable stage of Alzheimer's disease: A tale of shotgun lipidomics. J. Neurochem. 103(s1), 171-179. 13. Han, X. and Jiang, X. (2009) A review of lipidomic technologies applicable to sphingolipidomics and their relevant applications. Eur. J. Lipid Sci. Technol. 111, 39-52. 14. Gross, R.W. and Han, X. (2009) Shotgun lipidomics of neutral lipids as an enabling technology for elucidation of lipid-related diseases. Am. J. Physiol. – Endocrinol. Metab. 297, E297-303. 15. Han, X. (2009) Lipidomics: Developments and applications, J. Chromatogr. B 877, 2663. Chapters in Books: 1. Han, X. and Gross, R.W. (1991) Modulation of cardiac membrane fluidity by amphiphilic compounds and their role in the pathophysiology of myocardial infarction. In Drug and Anesthetic Effects on Membrane Structure and Function (Aloia, R. C., Curtain, C. C., & Gordon, L. M., Eds.), 225-243, Wiley-Liss, Inc. 2. Han, X. (1999) Chromatography. In The Encyclopedia of Molecular Biology (T. E. Creighton, ed.), 1st edition, John Wiley & Sons, New York. 3. Han, X. (2002) Chromatography. In The Encyclopedia of Molecular Biology (T. E. Creighton, ed.), 2nd edition, John Wiley & Sons, New York. 4. Han, X. and Holtzman, D.M. (2004) Sulfatide mass level in cerebrospinal fluid may be a potential biomarker for the diagnosis of very mild Alzheimer's dementia. In Research and Practice in Alzheimer's Disease and Cognitive Decline 9, 26-30. 5. Han, X. and Gross, R.W. (2005) Towards total cellular lipidome analysis by electrospray ionization mass spectrometry from a crude lipid extract of a biological sample. In Modern Techniques in Lipid Analysis by Liquid Chromatography/Mass Spectrometry and Related Techniques (W.C. Byrdwell, ed.), chapter 12, pp 488-509. AOCS Press, Champaign, IL. 6. Han, X. and Gross, R.W. (2006) Specific lipid alterations in Alzheimer's disease and diabetes: Shotgun global cellular lipidome analyses by electrospray ionization mass spectrometry using intrasource separation. In Functional Lipidomics (L. Feng and G. Prestwich, eds.), chapter 13, pp. 285-306, Marcel Dekker, New York. 7. Han, X. and Gross, R.W. (2006) Global cellular lipidome analyses by shotgun lipidomics using multi-dimensional mass spectrometry. In Lipid Analysis and Lipidomics: New Techniques and Applications (M.M. Mossoba, J.K.G. Kramer, J.T. Brenna, and R.E. McDonald, eds.), chapter 3, pp. 51-71, AOCS Press, Champaign, IL. 8. Han, X. and Gross, R.W. (2007) Free fatty acids and lipids. In Choice of Ionization for Analysis of Various Substances (Vol. 6 of Encyclopedia of Mass Spectrometry), 876-889, Elsevier Ltd. 9. Han, X. and Gross, R.W. (2007) New developments in multi-dimensional mass spectrometrybased shotgun lipidomics. In Metabolomics, Metabonomics and Metabolic Profiling (W. Griffiths, ed.), 136-163, The Royal Society of Chemistry, Cambridge, United Kingdom. 10. Gross, R.W. and Han, X. (2007) Lipidomics in diabetes and the metabolic syndrome. Methods Enz. (Lipidomics and Active Lipids: Specialized Analytical Methods and Lipids in Disease (H. A. Brown, ed.), vol. 433, chapter 4, 73-90, Elsevier Inc. 11. Han, X. (2009) Applications of ESI and MALDI to lipid analysis. In Electrospray and MALDI Mass Spectrometry: Fundamentals, Instrumentation, Practicalities, and Applications (R.B. Cole, ed.), in press, John Wiley & Sons, Inc., New Jersey. 12. Han, X. Cheng, H., Jiang, X. and Zeng, Y. (2009) Shotgun lipidomics analyses of brain tissue lipids. In Lipid-mediated Signal Transduction (E. Murphy and T. Rosenberger, eds.), in press, CRC Presses. 13. Kiebish, M.A., Han, X., and Seyfried, T.N. (2009) Examination of the brain mitochondrial lipidome using shotgun lipidomics. In Lipidomics (Methods in Molecular Biology) (D. Armstrong, ed), In press, The Humana Press, Inc. New Jersey. Book: William C. Christie and Xianlin Han (2009) LIPID ANALYSIS: Isolation, Separation, Identification, and Lipidomic Analysis. The Oliy Press, Bridgwater, England (In press). Manuscript Submitted or in Preparation: 1. Kanter, J.L., Ho, P. P., Johnson, A.M., Srinagesh, H.K., Narayana, S., Hur, E.M., He, Z., Han, X., Olsson, T., Han, M., Steinman, L., and Robinson, W.H. (2009) Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. Nat. Med. Submitted. 2. Li, M., Han, X., Jenkins, C., and Gross, R.W. (2009) Calcium-independent phospholipase A2 and hydrolyze cardiolipin and generate monolysocardiolipin, dilysocardiolipin, and free fatty acid. In preparation. 3. Cheung, M.C., Vaisar, T., Han, X., Heinecke, J.W., and Albers, J.J. (2009) Human PLTP carries proteinS linked to immunity and inflammation: Implications for protein–protein interactions in PLTP Particle assembly. J. Biol. Chem. Submitted. 4. Mancuso, D.J., Kotzbauer, P., Wozniak, D.F., Sims, H.S., Jenkins, C.M., Guan, S., Han, X., Yang, K., Sun, G., Malik, I., Conyers, S., Green, K.G., Schmidt, R.E., and Gross, R.W. (2009) Genetic ablation of calcium-independent phospholipase A2 leads to a progressive mitochondrial degenerative neuropathy characterized by markedly enlarged mitochondria, alterations in hippocampal cardiolipin molecular species, ubiquitin inclusions and progressive cognitive and sensorimotor dysfunction. J. Biol. Chem. Submitted. 5. Fox, T.E., Han, X., Young, M.M., Gardner, T.W., and Kester, M. (2009) Diabetes diminishes phosphatidic acid in the retina: Implications for reduced mTOR signaling and increased neuronal cell death in diabetic retinopathy. J. Biol. Chem. Submitted. 6. Aboulafiah-Etzion, S., Etzion, Y., DeBosch, B., Lupu, T.S., Han, X., Gross, R.W., and Muslin, A.J. (2009) Development of diabetic cardiomyopathy in mice lacking Akt2. J. Biol. Chem. Submitted. 7. Cheng, H., Sun, G., Yang, K., Gross, R.W., and Han, X. (2009) Selective desorption/ionization of sulfatides by matrix-assisted laser desorption/ionization mass spectrometry facilitated using 9aminoacridine as the matrix. In preparation. 8. Ye, H., Hill, J., Kauffman, J., and Han, X. (2009) Qualitative and quantitative characterization of protein products using iTRAQ and MALDI TOF/TOF mass spectrometry. Anal. Biochem. Submitted. Patents and Patent Applications: 1. Han, X. and Holtzman, D.M. (2006) Diagnostic for early stage Alzheimer's disease. United States Patent 7,015,044. Canada Patent 2,469,486. 2. Gross, R.W. and Han, X. (2007) Molecular fingerprinting of triglycerides in biological samples by electrospray ionization tandem mass spectrometry. United States Patent 7,306,952. 3. Gross, R.W. and Han, X. (2008) Multidimensional mass spectrometry of serum and cellular lipids directly from biologic extracts. United States Patent 7,510,880. 4. Gross, R.W. and Han, X. (2007) Enhanced medical treatment in diabetic cardiomyopathy. Patent application number: 11/539,136. 5. Gross, R.W. and Han, X. (2007) Methods for treatment of diabetic cardiomyopathy by administering iPLA2 and iPLA2 inhibitors resulting in increased cardiolipin levels and performing shotgun lipidomics analysis. Patent application number: US 2007265216. 6. Han, X. (2008) Lipid profile as a biomarker for early detection of neurological disorders. Patent application number: 12/179,809. 7. Gross, R.W., Sun, G., and Han, X. (2008) Multiplexing matrix-analyte stereoelectronic interactions for high throughput shotgun metabolomics. Patent application number: 28458-0001. Invited Lectures/Presentations (since 2003): 1. “Specific changes of sulfatides in very early AD: An electrospray ionization mass spectrometric study”. Center for Neurodegenerative Disease, Harvard Medical School, July 21, 2003. 2. “Sulfatide mass content as a potential biomarker for the diagnosis of very early Alzheimer’s disease”. Echigoyuzawa, Japan, August 26, 2003. 3. “Specific changes of sulfatides in very early AD: An electrospray ionization mass spectrometric study”. University of Tokyo, Japan, August 27, 2003. 4. “Shotgun lipidomics and studies on Alzheimer’s disease”. Department of Biochemistry, Saint Louis University, May 12, 2004. 5. “Towards fingerprinting cellular lipidomes directly from biological samples by two-dimensional electrospray ionization mass spectrometry”. 52ed ASMS conference, Nashville, TN, May 23-27, 2004. 6. “Shotgun lipidomics and studies on Alzheimer’s disease”. Department of Pharmacology, Pennsylvania State University - Hershey, July 20, 2004. 7. Towards fingerprinting cellular lipidomes directly from biological samples by intrasource separation and two-dimensional mass spectrometry. Oils and Fats International Congress and Exhibition, Kuala Lumpur, Malaysia, Sept 29-Oct 2, 2004. 8. “Quantitative analysis of triacylglycerol molecular species directly from crude lipid extracts by 2D ESI mass spectrometry”. Oils and Fats International Congress and Exhibition, Kuala Lumpur, Malaysia, Sept 29-Oct 2, 2004. 9. “Shotgun lipidomics and application for biomarker discovery in Alzheimer’s disease”. Asilomar Conference on Mass Spectrometry – Metabolite Profiling: Biomarker Discovery, Drug Efficacy and Fundamental Biochemistry, October 15-19, 2004, Asilomar, CA. 10. “Shotgun lipidomics: Principles and applications”. Department of Environment, University of California at Riverside, October 20, 2004. 11. “Shotgun lipidomics based on intrasource separation and multidimensional mass spectrometry: Principles and applications”. Keystone Symposium on Bioactive Lipids, Lipidomics and their Targets, Whistler, British Columbia, April 12-17, 2005. 12. “Shotgun lipidomics: Global analysis of cellular lipids directly from lipid extracts by twodimensional ESI mass spectrometry”. 96th AOCS annual meeting, Salt Lake City, UT, May 1-5, 2005. 13. Co-Chair the Symposium of Mass Spectrometry: Lipidomics, 96th AOCS annual meeting, Salt Lake City, UT, May 1-5, 2005. 14. “Shotgun lipidomics: Global analysis of cellular lipidomes by intrasource separation and multidimensional ESI mass spectrometry”. Lipidomics Workshop in Dresden, Dresden, Germany, May 20-21, 2005. 15. “Shotgun Lipidomics: Principles and Applications”. Department of Chemistry, Zhejiang University, China, September 27, 2005. 16. “What we have learned about Alzheimer’s disease from lipidomics”. School of Medicine, Zhejiang University, China, September 26, 2005. 17. “What lipidomics has revealed about Alzheimer’s disease”. Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, March 22, 2006. 18. “Shotgun lipidomics of cardiolipin molecular species in lipid extracts of biological samples”. 97th AOCS annual meeting, St. Louis, MO, April 30-May 3, 2006. 19. Co-Chair the Symposium of Mass Spectrometry of Lipids, 97th AOCS annual meeting, St. Louis, MO, April 30-May 3, 2006. 20. “What lipidomics has revealed about Alzheimer’s disease”. The Second Scientific Meeting of the Metabolomics Society, Boston, June 24 – 29, 2006. 21. “Shotgun Lipidomics: Principles and Applications”. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, July 27, 2006. 22. “Multi-dimensional mass spectrometry for lipid analysis”. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, July 27, 2006. 23. “Application of shotgun lipidomics in biological and biomedical studies”. Dalian Institute of 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. Chemical Physics, Chinese Academy of Sciences, July 27, 2006. “Shotgun lipidomics: ESI/MS analysis of cellular lipidomes directly from crude extracts of biological samples”. The International Chinese Mass Spectrometry Conference, Urumqi, Xinjiang, China, July 30-August 5, 2006. “Multi-dimensional mass spectrometry for lipid analysis”. The International Chinese Mass Spectrometry Conference, Urumqi, Xinjiang, China, July 30-August 5, 2006. “Shotgun lipidomics for cellular cardiolipin molecular species”. 17th International Mass Spectrometry Conference, Prague, Czech Republic, August 27-September 1, 2006. “Lipidomics in the study of Alzheimer’s disease”. Metabolomics Workshop (Metabolomic Approaches to Neurological Disorders), 36th Neuroscience Annual Meeting, Atlanta, Georgia, October 14-18, 2006. “Mechanisms responsible for sulfatide depletion in the early stage of Alzheimer's disease: A tale of shotgun lipidomics”. The Second ISN Special Neurochemistry Conference: Neural Glycoproteins and Glycolipids. Antigua, West Indies, Caribbean, December 1-5, 2006. “A story of cardiolipin told by shotgun lipidomics”. Midwest Mass Spectrometry Discussion Group Meeting, St. Louis, Missouri, December 13, 2006. “Alterations in cardiolipin content and molecular species composition link diabetic cardiomyopathy and mitochondrial dysfunction in murine models of diabetes”. Gordon Research Conference on Molecular & cellular biology of lipids, Waterville Valley, NH, July 22-27, 2007. “What shotgun lipidomics has revealed about Alzheimer’s disease”. Department of Biochemistry, University of Missouri-Columbia, MO, September 14, 2007. “A story of cardiolipin in diabetic cardiomyopathy told by shotgun lipidomics”. Department of Cell Physiology, Pennsylvania State University - Hershey, September 19, 2007. “Cardiolipin profiling of diabetic cardiomyopathy: A shotgun lipidomics study”. Advances in Metabolic Profiling, Select BioScience, Boston, MA, November 13-14, 2007. “A story of cardiolipin in diabetic cardiomyopathy told by shotgun lipidomics”. Department of Biology, Boston College, November 27, 2007. “A potential underlying cause of Alzheimer's disease: What we have learned from sulfatide depletion in AD”. The Alzheimer's Disease Research Center, Washington University School of Medicine, January 29, 2008. “A story of cardiolipin in diabetic cardiomyopathy told by shotgun lipidomics”. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, February 11, 2008. “A story of cardiolipin in diabetic cardiomyopathy told by shotgun lipidomics”. Center for Cardiovascular Research, Division of Cardiology, Department of Internal Medicine, Washington University School of Medicine, February 14, 2008. “The underlying principles of shotgun lipidomics”. Second Singapore Lipid Symposium, March 5-7, 2008. “A story of cardiolipin in diabetic cardiomyopathy told by shotgun lipidomics”. Institute for Nutritional Science, Chinese Academy of Science, Shanghai, March 10, 2008. “The role of sulfatide in the pathogenesis of Alzheimer's disease: What we have learned from sulfatide depletion in AD”. Institute of Neuroscience, Department of Neurology, Peking University, March 25, 2008. “The underlying principles of shotgun lipidomics”. Institute of Neuroscience, Department of Neurology, Peking University, March 26, 2008. 42. “Lipidomics and Alzheimer’s disease”. Society of Biological Psychiatry Workshop 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. (Metabolomics and Lipidomics of Neuropsychiatric Disorders: Emerging Data), the Society of Biological Psychiatry's 63rd Annual Convention, Washington, DC, May 1-3, 2008. “Development and discovery of shotgun lipidomics: An update”. The 5th LIPID MAPS Annual Meeting, La Jolla, CA, May 5-6, 2008. “Alkaline methanolysis of lipid extracts extends shotgun lipidomics analyses to the low abundance regime of cellular sphingolipids”. 99th AOCS annual meeting, Seattle, WA, May 1821, 2008. Co-Chair the Symposium of Mass Spectrometric Analysis of Lipids, 99th AOCS annual meeting, Seattle, WA, May 18-21, 2008. “Altered cardiolipin profile in diabetic cardiomyopathy: A shotgun lipidomics study”. The 2nd International Chinese Conference for Mass Spectrometry, Taipei, Taiwan, June 25-July 1, 2008. “What’s the matter with the cardiolipin molecular species profile: A lesson learnt from shotgun lipidomics”. 4th International Scientific, Medical & Family Conference of Barth Syndrome: On Track Toward a Cure, Clearwater, FL, July 23-26, 2008. “A story of cardiolipin in diabetic cardiomyopathy told by shotgun lipidomics”. Department of Biochemistry, St. Louis University, September 17, 2008. “Lipidomics”. The Pathobiology Research Unit, Department of Pediatrics, Washington University School of Medicine, October 21, 2008. “A potential underlying cause of Alzheimer's disease: What we have learned from sulfatide depletion in AD”. Abbot Labs, Chicago, November 11, 2008. “The underlying principles and applications of global cellular lipid analysis for biomarker development using shotgun lipidomics”. Eastern Analytical Symposium & Exposition (EAS 2008), Somerset, New Jersey, November 17-20, 2008. “New developments in shotgun lipidomics: An update”. DICP Symposium (XIX) on Frontier of Bioanalytical Techniques: Challenge of Metabonomics and Other Omics, Dalian, China, November 29-30, 2008. “Lipidomics platforms at Washington University and beyond”. Metabolomics Network for Drug Response Phenotype, 2nd Annual Meeting, Bethesda, MD, December 16 – 17, 2008 “The underlying principles of shotgun lipidomics”. Lipidomics and Lipids in Mass Spectrometry, The Sanibel Conference, St. Petersburg, FL, January 23-26, 2009. “Shotgun lipidomics reveals altered lipid content/composition and identifies the responsible biochemical mechanism(s)”. The Functional Genomics Consortium Symposium at Kansas State University, Kansas, March 4-5, 2009. “The underlying principles of shotgun lipidomics and its applications for biomedical research”. The UC Davis Genome Center, University of California at Davis, March 20, 2009. “The role of sulfatide in the pathogenesis of Alzheimer's disease: What we have learned from sulfatide depletion in AD by using shotgun lipidomics”. Frontier Lipidology: Lipidomics in Health and Disease, Gothenburg, Sweden, May 10-13, 2009. “Introduction of multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS)”. The Bioanalytical Research Center, Leiden University, Netherlands, May 18, 2009. “Applications of MDMS for biomedical research”. The Bioanalytical Research Center, Leiden University, Netherlands, May 19, 2009. “Lipidomics and biomedical research”. MSTP MAP Seminar series, Washington University School of Medicine, June 15, 2009. “Introduction to metabolomics/lipidomics”. GEMS Seminar series, Division of Biostatistics, Washington University School of Medicine, August 19, 2009. “Shotgun lipidomics and Alzheimer’s disease”. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, August 25, 2009. “The role of sulfatide in the pathogenesis of Alzheimer's disease: What we have learned from sulfatide depletion in AD by using shotgun lipidomics”. Institute for Nutritional Science, Chinese Academy of Science, Shanghai, August 27, 2009. 64. “Sulfatide and Alzheimer’s disease”. Novel Strategies for Intervention in Neurodegenerative Diseases, The 22nd Biennial meeting of the ISN/APSN Joint Meeting Satellite Conference. August 30 - September 2, 2009, Taipei, Taiwan. 65. “A newly-emerged discipline in the front of biological research: Introduction to lipidomics”. Zhejing University, Hangzhou, China, September 11, 2009. 66. “Shotgun lipidomics and its Applications on Biomedical Research”. Institute of Biophysics, Chinese Academy of Sciences, Beijing, September 23, 2009. 67. “The underlying principles of shotgun lipidomics and its applications for biomedical research”. Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL, October 8, 2009. 68. “The role of sulfatide in the pathogenesis of Alzheimer's disease: What we have learned from sulfatide depletion in AD by using shotgun lipidomics”. Midwest Mass Spectrometry Discussion Group Meeting, St. Louis, Missouri, October 20, 2009. 69. “The role of sulfatide in the pathogenesis of Alzheimer's disease: What we have learned from sulfatide depletion in AD by using shotgun lipidomics”. Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, November 6, 2009. Abstracts and/or Oral Presentation (since 2003) 1. Finck, B.N., Han, X., Kovacs, A., Gross, R.W. and Kelly, D.P.: A critical role for PPARmediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation of phenotype by dietary fat content. Keystone conference, 2003. 2. Burns, J.M., Xiong, C., Church, J., Fagan, A.M., Han, X., Head, D., Fotenos, A., Marcus, D., Snyder, A.Z., Buckner, R.L., Holtzman, D.M., Morris, J.C. Combined biomarkers in discriminating nondemented aging from early Alzheimer disease. AAN meeting, San Francisco, CA, April 24 - May 1, 2004. 3. Cheng, H. and Han, X. The effects of apoE on the lipidome of mouse peripheral nervous system: A two-dimensional electrospray ionization mass spectrometric study. 52ed ASMS conference, Nashville, TN, May 23-27, 2004. 4. Gross, R.W., Cheng, H., Abendschein, D.R. and Han, X. Identification of plasmalogen as a major phospholipid component in human myocardium: A study using two-dimensional electrospray ionization mass spectrometry. 52ed ASMS conference, Nashville, TN, May 23-27, 2004. 5. Fagan, A.M., Christopher, E., Spinner, M., Han, X., Morris, J.C. and Holtzman, D.M. Probing for antecedent biomarkers of Alzheimer’s disease through analysis of CSF from middle-aged individuals. The 9th International Conference on Alzheimer's Disease and Related Disorders, Philadelphia, PA, July 17 - 22, 2004. Neurobiol. Aging, 25 (2004), S364-S365. 6. Cheng, H. and Han, X. The effects of apoE on the lipidome of mouse peripheral nervous system. 34th Neuroscience Annual Meeting, San Diego, CA, October 23-27, 2004. 7. Fagan, A.M., Christopher, E., Spinner, M., Han, X., Morris, J.C. and Holtzman, D.M. Probing for antecedent biomarkers of Alzheimer’s disease through analysis of CSF from middle-aged individuals. 34th Neuroscience Annual Meeting, San Diego, CA, October 23-27, 2004. 8. Maysinger, D., Holmes, M., Epand, R.M., Han, X., Holtzman, D.M., and Diamond, J. Different mechanisms underlie the failure of compensatory nerve sprouting in apoE KO mice and in aged normal mice. AAN meeting, San Diego, CA, April 1 - 8, 2006. 9. Cheng, H., Jiang, X., and Han, X. Identification of the specific role of apolipoprotein E gene in the lipid homeostasis of mouse dorsal root ganglia: A shotgun lipidomics study. The Second ISN Special Neurochemistry Conference: Neural Glycoproteins and Glycolipids. Antigua, West Indies, Caribbean, December 1-5, 2006. J. Neurochem. 99 (S1) (2006), 5. 10. Dawson, G., Kilkus, J.P., Dawson, S., Berdyshev, E., and Han, X. Ceramide levels are regulated differently in neurons and glia. The Second ISN Special Neurochemistry Conference: Neural Glycoproteins and Glycolipids. Antigua, West Indies, Caribbean, December 1-5, 2006. J. Neurochem. 99 (S1) (2006), 7. 11. Jiang, X. and Han, X. Shotgun sphingolipidomics: Electrospray ionization mass spectrometric analysis and quantitation of cellular sphingolipidomes from crude extracts of biological samples after treatment with lithium methoxide. The Second ISN Special Neurochemistry Conference: Neural Glycoproteins and Glycolipids. Antigua, West Indies, Caribbean, December 1-5, 2006. J. Neurochem. 99 (S1) (2006), 15-16. 12. Zeng, Y., Cheng, H., and Han, X. Sulfatide induced apoptosis in neuroblastoma cells. The Second ISN Special Neurochemistry Conference: Neural Glycoproteins and Glycolipids. Antigua, West Indies, Caribbean, December 1-5, 2006. J. Neurochem. 99 (S1) (2006), 35. 13. Jiang, X., Cheng, H., Yang, K., Gross, R.W., and Han, X. Alkaline methanolysis of lipid extracts extends shotgun lipidomics analyses to the low abundance regime of cellular sphingolipids. The 4th International Charleston Ceramide Conference, Asilomar, CA, March 7-11, 2007. 14. Zeng, Y., Cheng, H., and Han, X. Endosomes and lysosomes play distinct roles in sulfatideinduced neuroblastoma apoptosis: Potential mechanisms contributing to abnormal sulfatide metabolisms in related neuronal diseases. The 4th International Charleston Ceramide Conference, Asilomar, CA, March 7-11, 2007. 15. Jiang, X., Cheng, H., Yang, K., Gross, R.W., and Han, X. Shotgun sphingolipidomics: Electrospray ionization mass spectrometric analysis and quantitation of cellular sphingolipidomes from crude extracts of biological samples after treatment with lithium methoxide. 54th ASMS conference, Indianapolis, IN, June 3-7, 2007. 16. Kiebish, M.A., Han, X., Cheng, H., and Seyfried, T.N. Mitochondrial lipid and enzyme abnormalities in mouse brain tumors. Mitochondrial Medicine 2007, San Diego, CA, June 13-16, 2007. 17. Kiebish, M.A., Han, X., Cheng, H., and Seyfried, T.N. Analysis of non-synaptic and synaptic mouse brain mitochondrial lipids and electron transport enzyme activities. Mitochondrial Medicine 2007, San Diego, CA, June 13-16, 2007. 18. Han, X., Yang, K., and Gross, R.W. Alterations in cardiolipin content and molecular species composition link diabetic cardiomyopathy and mitochondrial dysfunction in murine models of diabetes. Gordon Research Conference on Molecular & cellular biology of lipids, Waterville Valley, NH, July 22-27, 2007. 19. Kiebish, M.A., Han, X., Cheng, H., and Seyfried, T.N. Mitochondrial lipidome and electron transport chain abnormalities in experimental mouse brain tumors. 21st Biennial International Society for Neurochemistry and 38th Annual conference of American Society for Neurochemistry, Cancun, Mexico, August 19-24, 2007. J. Neurochem. 102 (S1) (2007), 64. 20. Kiebish, M.A., Han, X., Cheng, H., and Seyfried, T.N. Analysis of non-synaptic and synaptic mitochondrial lipidome and electron transport chain activities. 21st Biennial International Society for Neurochemistry and 38th Annual conference of American Society for Neurochemistry, Cancun, Mexico, August 19-24, 2007. J. Neurochem. 102 (S1) (2007), 65. 21. Sun, Y., Ran, H., Zamzow, M., Quinn, B., Williams, M.T., Vorhees, C.V., Witte, D.P., Cheng, H., Han, X., and Grabowski, G.A. Saposin B deficiency in mice leads to sulfatide and lactosylceramide accumulation and slowly developed neurological deficit. The 57th Annual Meeting of the American Society of Human Genetics, San Diego, CA, October 23-27, 2007. 22. Han, X., Yang, K., and Gross, R.W. Alterations in cardiolipin content and molecular species composition link diabetic cardiomyopathy and mitochondrial dysfunction in murine models of diabetes. Mass Spectrometry in the Heartland Conference, Ozark, MO, October 25-26, 2007. 23. Gryniewicz, C., Han, X., Hill, J., Kauffman, J.F., and Ye, H. Detection of protein modifications and counterfeit protein pharmaceuticals using iTRAQ and MALDI TOF/TOF mass spectrometry. AAPS Annual Meeting & Exposition, Washington DC, November 11-15, 2007. 24. Kiebish, M.A., Han, X., Cheng, H., and Seyfried, T.N. Mitochondrial lipidome and electron transport chain alterations in non-metastatic and metastatic murine brain tumors. 39th Annual conference of American Society for Neurochemistry, San Antonio, Texas, March 1-5, 2008. 25. Dang, D., Chun, S., Burkitt, K., Cruz-Correa, M., Han, X., and Dang, L.H. (2008) HIF-as promote mitochondrial cardiolipin synthesis and respiration efficiency. AACR Annual Meeting, San Diego, April 12-16, 2008. 26. Kiebish, M.A., Chuang, J.H., Bell, R., Phan, T., Ames, W., Yang, K., Seyfried, T.N., and Han, X. (2009) A web-based real-time dynamic simulation of cardiolipin remodeling – A new tool for lipidomic analysis. Lipidomics and Lipids in Mass Spectrometry, The Sanibel Conference, St. Petersburg, FL, January 23-26, 2009. 27. Kiebish, M.A., Sambandam, N., Young, D.M., Wozniak, D., Lehman, J.J., and Han, X. (2009) Chronic caloric restriction alleviates a loss of sulfatide content in the PGC-1alpha KO mouse cortex through a potential apoE mediated mechanism. ASN 40th Annual Meeting, Charleston, SC, March 7-11, 2009. 28. Yang, K., Cheng, H., Gross, R.W., and Han, X. (2009) Automated lipid identification and quantification by multi-dimensional mass spectrometry-based shotgun lipidomics. 57th ASMS conference, Philadelphia, PA, May 30-June 4, 2009.