Xianlin Han, PhD

Professor

Personal Statement:

I am an internationally-renowned investigator in the fields of lipidomics, lipid metabolism, and lipid biochemistry. I have developed expertise in broad areas of research, such as neuroscience, diabetes, and metabolic biochemistry. The mass spectrometric techniques for lipidomics developed by our group, collectively termed “multi-dimensional mass spectrometry-based shotgun lipidomics” with unparalleled high sensitivity and comprehensive coverage, have been widely used to identify altered lipid metabolism, trafficking, and homeostasis, and biomarkers under patho(physio)logical conditions. The current interests of my laboratory research focus on Alzheimer’s disease, diabetic neuropathy, and mitochondrial dysfunction in diabetic hearts. As an investigator or co-investigator on over thirty previous NIH-funded grants, I have successfully produced multiple peer-reviewed publications from each project, resulting in a total of over 300 peer-reviewed publications. It is gratifying that my contributions have received over 34,000 citations (over half are since 2015) with an h-index of 88 (Google Scholar, 2021).

Education

Year	Degree	Discipline	Institution
1982	BS	Chemistry	Zhejiang University, P.R. , China
1985	MS	Chemical Thermodynamics	Zhejiang University, P.R. , China
1987	MA	Physical Chemistry	Washington University, St. Louis , MO
1990	PhD	Biophysical and Bioanalytical Chemistry	Washington University, St. Louis , MO

Research

Our research focuses on functional lipidomics, that is, uncovering alterations in lipid metabolism, signaling, and homeostasis that occur under patho(physio)logical conditions such as Alzheimer’s disease (AD), diabetes, and aging by lipidomics; identifying the underlying molecular and biochemical mechanisms; unraveling the consequences induced by these lipid changes; and developing drug targets for the diseases based on the mechanistic and consequence studies. Lipidomics, which facilitates large-scale analysis of cellular lipidomes based on the principles and techniques of analytical chemistry, allows us to comprehensively and effectively determine alterations in lipid metabolism, signaling, and homeostasis under different conditions.

Our laboratory is one of the world-leading research groups on lipidomics. We have developed an enabling technology with in-house software programs termed “multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL)”, initiated in the early 1990s and still under constant development. The MDMS-SL technology provides modular, robust, and label-free quantification of lipids. At its current stage, the technology enables us to identify and quantify over 50 lipid classes, over 95% of lipid mass content, and thousands of individual lipid molecular species from limited amounts of biological samples in an accurate (>90% reproducibility) and relatively high throughput fashion. By using lipidomics, we have developed a few research projects (supported with NIH funds and other sources) including AD and diabetes-associated dementia, as well as multiple minor translational research projects such as anesthetics-induced neurotoxicity and cancer biomarkers. By using our enabling lipidomics technology, we have also established numerous (inter)national collaborations on a variety of research areas.

Awards & Accomplishments

2003	Memory Ride Prize
2017-Present	Methodist Hospital Foundation Chair in Aging Studies and Research, University of Texas Health Science Center at San Antonio
2018	University of Texas System STARs Award
Guest Professors	Changchun Institute of Applied Chemistry, Chinese Academy of Sciences; Soochow University; and Oil Crop Research Institute, Chinese Academy of Agricultural Sciences
2019-present	Associate Editor, Journal of Lipid Research

Affiliations

Barshop Institute for Longevity and Aging Studies

Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases

Department of Medicine, Division of Diabetes

University of Texas Health Science Center at San Antonio

Lab Members

	Dr. Juan Pablo Palavicini	Assistant Professor/Research
	Dr. Estrella S. Chocron	Instructor/Research
	Dr. Shulan Qiu	Instructor/Research
	Dr. Meixia Pan	Research Scientist – Senior, Lab Manager
	Dr. Xiaohong Kong	Research Scientist – Senior
	Dr. Hanmei Bao	Postdoctoral Fellow
	Dr. Sijia He	Postdoctoral Fellow
	Cord Carter	Graduate Student
	Xin Li	Graduate Student
	Carly Alyce Tompkins	Graduate Student
	Ziying (Zoey) Xu	Graduate Student
	Sherry G. Dodds	Research Associate – Senior
	Hu Wang	Research Associate – Senior
	Anindita Bhattacharjee	Research Associate
	Charles Chao Qin	Research Associate

News

Dr. Han is the University of Texas System STARs Awardee.

Drs. Han and Seshadri received ~$3.5 million from the NIH National Institute on Aging to unravel the mechanisms by which APOE2 confers neuroprotection against aging and AD.

Dr. Han received ~$2.4 million the NIH National Institute on Aging to mechanistically study astrogliosis and microgliosis induced by sulfatide deficiency occurred in the earliest clinically-recognizable stages of Alzheimer’s disease and aging.

Dr. Han serves as the core or project leaders in several recent NIH awards including U54, U19, and P30 grants.

Publications

(Published in the last fiscal year)

1.	Wang, C., Palavicini, J.P., and Han, X. (2021) A lipidomics atlas of selected sphingolipids in multiple mouse nervous system regions. Int. J. Mol. Sci. 22, 11358.
2.	Liu, C.-C., Murray, M.E., Li, X., Zhao, N., Wang, N., Heckman, M.G., Shue, F., Martens, Y., Li, Y., Raulin, A.C., Rosenberg, C.L., Doss, S.V., Zhao, J., Wren, M., Jia, L., Ren, Y., Ikezu, T.C., Lu, W., Fu, Y., Caulfield, T., Trottier, Z.A., Knight, J., Chen, Y., Linares, C., Wang, X., Kurti, A., Asmann, Y.W., Wszolek, Z.K., Smith, G.E., Vemuri, P., Kantarci, K., Knopman, D.S., Lowe, V.J., Jack Jr., C.R., Parisi, J.E., Ferman, T.J., Boeve, B.F., Graff-Radford, N.R., Petersen, R.C., Younkin, S.G., Fryer, J.D., Wang, H., Han, X., Frieden, C., Dickson, D.W., Ross, O.A., and Bu, G. (2021) APOE3-Jacksonville (V236E) variant reduces self-aggregation and risk of dementia: Implications for therapeutic strategy. Sci. Transl. Med. 13, eabc9375.
3.	Zhao, J., Lu, W., Ren, Y., Fu, Y., Martens, Y.A., Shue, F., Davis, M.D., Wang, X., Chen, K., Li, F., Liu, C.C., Graff-Radford, N.R., Wszolek, Z.K., Younkin, S.G., Brafman, D.A., Ertekin-Taner, N., Asmann, Y.W., Dickson, D.W., Xu, Z., Pan, M., Han, X., Kanekiyo, T., and Bu, G. (2021) Apolipoprotein E regulates lipid metabolism and α-synuclein pathology in human iPSC-derived cerebral organoids. Acta Neuropathol. doi: 10.1007/s00401-021-02361-9.
4.	Qiu, S., Palavicini, J.P., Wang, J., Gonzalez, N.S., He, S., Dustin, E., Zou, C., Ding, L., Bhattacharjee, A., van Skike, C.E., Galvan, V., Dupree, J.L., and Han, X. (2021) Adult-onset CNS sulfatide deficiency is sufficient to cause Alzheimer’s disease-like neuroinflammation and cognitive impairment. Mol. Neurodegener. 16, 64.
5.	Jin, R., Hao, J., Yi, Y., Yin, D., Hua, Y., Li, X., Bao, H., Han, X., Egilmez, N., Sauter, E., and Li, B. (2021) Dietary fats high in linoleic acids impair antitumor T-cell responses by inducing E-FABP-mediated mitochondrial dysfunction. Cancer Res. 81, 5296-5310
6.	Nho, K., Kueider-Paisley, A., Arnold, M., MahmoudianDehkordi, S., Risacher, S.L., Louie, G., Blach, C., Baillie, R., Han, X., Kastenmüeller, G., Doraiswamy, P.M., Kaddurah-Daouk, R., and Saykin, A.J. (2021) Serum metabolites associated with brain amyloid-β deposition, cognition, and dementia progression. Brain Commun. 3, fcab139.
7.	Horgusluoglu-Moloch, E., Wang, M., Neff, R., Song, W.-M., Wang, Q., Arnold, M., Krumsiek, J., Galindo-Prieto, B., Ming, C., Nho, K., Kastenmüller, G., Han, X., Baillie, R., Zeng, Q., Andrews, S., Cheng, H., Hao, K., Goate, A., Bennett, D.A., Saykin, A.J., Kaddurah-Daouk, R., and Zhang, B. (2021) Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer’s disease. Alz. Dement. doi: 10.1002/alz.12468.
8.	Waldhart, A.N., Muhire, B., Johnson, B., Pettinga, D., Madaj, Z.B., Wolfrum, E., Dykstra, H., Wegert, V., Pospisilik, J.A., Han, X., and Wu, N. (2021) Excess dietary carbohydrate affects mitochondrial integrity as observed in brown adipose tissue. Cell Rep. 36, 109488.
9.	Fitz, N.F., Nam, K., Wolfe, C.M., Letronne, F., Playso, B.E., Iordanova, B.E., Kozai, T.D.Y., Biedrzycki, R.J., Kagan, V.E., Tyurina, Y.Y., Han, X., Lefterov, I., and Koldamova, R. (2021) Phospholipid composition of APOE lipoproteins affects microglia activation in an isoform-specific manner. Nat. Commun. 12, 3416.
10.	MahmoudianDehkordi, S., Ahmed, A.T., Bhattacharyya, S., Han, X., Baillie, R.A., Skime, M.K., St John-Williams, L., Moseley, A.M., Thompson, W.J., Louie, G., Riva-Posse, P., Craighead, W.E., McDonald, W., Krishnan, R., Rush, A.J., Frye, M.A., Dunlop, B.W., Weinshilboum, R.M., and Kaddurah-Daouk, R. (2021) Alterations in acylcarnitines, amines and lipids inform about mechanism of action of citalopram/escitalopram in major depression. Transl. Psychiatry 11, 153.
11.	Sun, G.Y., Appenteng, M.K., Li, R., Woo, T., Bo, Y., Qin, C., Pan, M., Cieślik, M., Cui, J., Fritsche, K.L., Gu, Z., Will, M., Beversdorf, D., Adamczyk, A., Han, X., and Greenlief, C.M. (2021) Docosahexaenoic acid (DHA) supplementation alters phospholipid species and lipid peroxidation products in adult mouse brain, heart, and plasma. Neuromol. Med. 23, 118-129.
12.	Hu, C., Du, Y., Xu, X., Li, H., Duan, Q., Xie, Z., Wen, C., and Han, X. (2021) Lipidomics revealed aberrant metabolism of lipids including FAHFAs in renal tissue in the progression of lupus nephritis of a murine model. Metabolites, 11, 142.
13.	Kumar, A., Sundaram, K., Mu, J., Dryde, G., Sriwastva, M., Lei, C., Zhang, L., Qiu, X., Xu, F., Yan, J., Zhang, X., Park, J., Merchant, M., Bohler, H., Wang, B., Qin, C., Xu, Z., Han, X., McClain, C., Teng, Y., and Zhang, H.-G. (2021) High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance. Nat. Commun. 12, 213.
14.	Hu, C., Zhang, J., Hong, S., Li, H., Lu, L., Xie, G., Luo, W., Du, Y., Xie, Z., Han, X., and Wen, C. (2021) Oxidative stress-induced aberrant lipid metabolism is an important causal factor for dysfunction of immunocytes from patients with systemic lupus erythematosus. Free Radic. Biol. Med. 163, 210-219. **These are the corresponding authors.
15.	Shannon, C.E., Ragavan, M., Palavicini, J.P., Fourcaudot, M., Bakewell, T., Valdez, I.A., Ayala, I., Jin, E.S., Muniswamy, M., Han, X., Merritt, M.E., and Norton, L. (2021) Insulin resistance is mechanistically linked to hepatic mitochondrial remodeling in nonalcoholic fatty liver disease. Mol. Metab. 45, 101154.
16.	Shu, Y., Hassan, F., Coppola, V., Baskin, K.K., Han, X., Mehta, N.K., Ostrowski, M.C., and Mehta, K.D. (2021) Hepatocyte-specific PKCβ deficiency protects against high-fat diet-induced nonalcoholic hepatic steatosis. Mol. Metab. 44, 101133.
17.	Köfeler, H., Ahrends, R., Baker, E.S., Ekroos, K., Han, X., Hoffmann, N., Holčapek, M., Wenk, M.R., and Liebisch, G. (2021) Recommendations for good practice in mass spectrometry based lipidomics. J. Lipid Res. doi.org/10.1016/j.jlr.2021.100138
18.	Han, X. and Ye, H. (2021) An overview of lipidomic analysis of triglyceride molecular species in biological lipid extracts. J. Agric. Food Chem. 69, 8895-8909.
19.	Köfeler, H.C., Eichmann, T.O., Ahrends, R., Bowden, J.A., Danne-Rasche, N., Dennis, E.A., Fedorova, M., Griffiths, W.J., Han, X., Hartler, J., Holčapek, M., Jirásko, R., Koelmel, J.P., Ejsing, C.S., Liebisch, G., Ni, Z., O’Donnell, V.B., Quehenberger, O., Schwudke, D., Shevchenko, A., Wakelam, M.J.O., Wenk, M.R., Wolrab, D., and Ekroos, K. (2021) Quality Control Requirements for the correct Annotation of Lipidomics Data. Nat. Commun. 12, 4771.
20.	Pan, M., Qin, C., and Han, X. (2021) Quantitative analysis of polyphosphoinositide, bis(monoacylglycerol)phosphate, and phosphatidylglycerol species by shotgun lipidomics after methylation. Methods Mol. Biol. (Shotgun Lipidomics: Methods and Protocols, Ed. Fong-Fu Hsu) 2306, 77-91.
21.	Pan, M., Qin, C., and Han, X. (2021) “Lipid metabolism and lipidomics applications in cancer research” Adv. Exp. Med. Biol. (Lipid Metabolism in Tumor Immunity, Ed. Yongsheng Li), 1316, 1-24.
22.	Wang, J., Wang, C., and Han, X. (2021) Mass spectrometry-based shotgun lipidomics for cancer research. (Cancer Metabolomics, Ed: Hu) Ad. Exp. Med. Biol.1280, 39-55.
23.	Qin, C., Pan, M., and Han, X. (2021) A detergent-free method for preparation of lipid rafts for the shotgun lipidomics study. Methods Mol. Biol. (Lipid rafts – Methods of isolation, visualization, and functional analysis, Ed. Erhard Bieberich), 2187, 27-35.
24.	Aviram, R., Wang, C., Han, X., and Asher, G. (2021) A lipidomics view of circadian biology. Methods Mol. Biol. 2130, 157-168. **These are the corresponding authors.
25.	Baloni, P., Funk, C.C., Yan, J., Yurkovich, J.T., Alexandra Kueider-Paisley, A., Nho, K., Heinken, A., Jia, W., Mahmoudiandehkordi, S., Louie, G., Saykin, A.J., Arnold, M., Kastenmüller, G., Griffiths, W.J., Thiele, I., Kaddurah-Daouk, R., Doraiswamy, P.M., Blach, C., Moseley, A., Thompson,J.W., Welsh-Balmer, K., Plassman, B., Bhattacharyya, S., Han, X., Baillie, R., Fiehn, O., Barupal, D., Meikle, P., Mazmanian, S., Kling, M., Shaw, L., Trojanowski, J., Toledo, J., van Duijin, C., Hankemier, T., Wishart, D., Brinton, R., Chang, R., Farrer, L., Au, R., Qiu, W., Würtz, P., Mangravite, L., Krumsiek, J., Newman, J., Zhang, B., Moreno, H., and Price, N.D. (2020) Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease. Cell Rep. Med. 1, 100138.
26.	Huynh, K., Lim, W.L.F., Giles, C., Jayawardana, K.S., Salim, A., Mellett, N.A., Smith, A., Olshansky, G., Drew, B.G., Chatterjee, P., Martins, I., Laws, S.M., Bush, A.I., Rowe, C.C., Villemagne, V.L., Ames, D., Masters, C.L., Arnold, M., Nho, K., Saykin, A.J., Baillie, R., Han, X., Kaddurah-Daouk, R., Martins, R.N., and Meikle, P.J. (2020) Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease. Nat. Commun. 11, 5698.
27.	Shinohara, M., Kanekiyo, T., Tachibana, M., Kurti, A., Shinohara, M., Fu, Y., Zhao, J., Han, X., Sullivan, P.M., Rebeck, W.G., Fryer, J.D., Heckman, M.G., and Bu, G. (2020) APOE2 is associated with longevity independent of Alzheimer’s disease. eLife 9, e62199.
28.	Palavicini, J.P., Chen, J., Wang, C., Wang, J., Qin, C., Baeuerle, E., Wang, X., Woo, J.A., Kang, D.E., Musi, N., Dupree, J.L., and Han, X. (2020) Early disruption of nerve mitochondrial and myelin lipid homeostasis in obesity-induced diabetes. JCI Insight, 5, e137286.
29.	Rodriguez-Ayala, E., Gallegos-Cabrales, E.C., Rodriguez-Arellano, M.E., Gonzalez-Lopez, L., Laviada-Molina, H.A., Salinas-Osornio, R.A., Leal-Berumen, I., Escudero-Lourdes, C., Escalante-Araiza, F., Buenfil-Rello, F.A., Peschard, V.-G., Laviada-Nagel, A., Pinto-Gutierrez, M., Veloz-Garza, R.A., Martinez-Hernandez, A., Barajas-Olmos, F.M., Molina-Segui, F., Gonzalez-Ramirez, L., Espadas-Olivera, R., Lopez-Muñoz, R., Arjona-Villicaña, R.D., Hernandez-Escalante, V.M., Nava-Gonzalez, E.J., Gaytan-Saucedo, J.F., Vaquera, Z., Acebo-Martinez, M., Gastelum-Ibarra, J., Cornejo-Barrera, J., Castillo-Pineda, J.C., Murillo-Ramirez, A., Diaz-Tena, S.P., Figueroa-Nuñez, B., Garzon-Zamora, R., Viveros-Paredes, J.M., Ángeles-Chimal, J., Santa-Olalla Tapia, J., Remes-Troche, J.M., Valdovinos-Chavez, S.B., Huerta-Avila, E.E., Commuzie, A.G., DeFronzo, R.A., Haack, K., Han, X., Orozco, L., Weintraub, S., Kent Jr., J.W., Cole, S.A., and Bastarrachea, R.A. (2020) Towards precision medicine: defining and characterizing adipose 1 tissue dysfunction to identify early immunometabolic risk in 2 symptom-free adults from the GEMM family study. Adipocyte, 9, 153-169.