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:
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 b peptides and sulfatides and to identify the molecular mechanisms leading to the amyloid b 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 1.8 Cal. Months NIH/NHLBI $212,764
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 post-translational 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 Subclass-Specific 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 La-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 b-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 ß-Cell 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. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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 acid-induced ion transport. Biochemistry 37, 9497-9508.
22. 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-3-phosphate dehydrogenase. Biochim. Biophys. Acta 1414, 95-107.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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 PPARa overexpression mimics that caused by diabetes mellitus. J. Clin. Invest. 109, 121-130.
29. 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. 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.
31. 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.
32. Jenkins, C.M., Han, X., Mancuso, D.J., and Gross, R.W. (2002) Identification of iPLA2b, and not iPLA2g, 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.
33. 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.
34. 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.
35. 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 PPARa-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation of phenotype by dietary fat content. Proc. Natl. Acad. Sci. USA 100, 1226-1231.