Libin Xu

Associate Professor, Medicinal Chemistry

Department of Medicinal Chemistry, Medicinal Chemistry Faculty, School Faculty, Xu Lab

Telephone: (206) 543-1080

Office Location: HSB, H-172P

Website: Xu Lab

Expertise:

Analytical Techniques, Central Nervous System, Drug Metabolism, Infectious Diseases, Lipid metabolism in human diseases, Neuroscience, Toxicology

Education

Postdoctoral training, Vanderbilt University
Ph.D. in Organic Chemistry, University of Illinois at Chicago
B.Sc. in Chemistry, Nankai University

Courses Taught

MEDCH/PCEUT 327
MEDCH 562
MEDCH 529
MEDCH 541
MEDCH 582
MEDCH 500

Research Interests

Mechanisms and products of lipid oxidation
Cholesterol biosynthesis disorders, in particular, Smith-Lemli-Opitz syndrome
Effect of drugs on lipid metabolism
Metabolomics and Lipidomics using ion mobility-mass spectrometry
Lipid metabolism in neurodevelopment
Mechanisms of antibiotic resistance

Taking Students: Yes

Biography

Dr. Xu was trained as an organic chemist early in his career, but during his postdoctoral training at Vanderbilt University, his research expanded to chemistry and biology of lipid peroxidation underlying human diseases, as well as mass spectrometry-based lipidomics.

The Xu lab is interested in the consequences of unusual lipid metabolism and oxidation processes on the nervous system, which could result from genetic mutations or small molecule interference. The lab aims to develop interventions that could ameliorate or reverse the adverse effects of the disrupted lipid homeostasis and oxidized lipids. The Xu lab is also interested in elucidating the contribution of altered lipid metabolism to antibiotic resistance in bacterial pathogens using mass spectrometry and molecular biology methodologies, aiming to develop strategies to re-sensitize the resistant bacteria. On the analytical chemistry side, the Xu Lab develops novel methodologies for the analysis of lipids, metabolites, drugs, and drug metabolites using ion mobility-mass spectrometry to meet the needs of our biological problems.

Dr. Xu is the recipient of the NIH Pathway to Independence Award from NICHD in 2012 and the Young Investigator Award from the Society for Free Radical Biology and Medicine in 2011. He is also the inaugural recipient, together with Prof. Brian Werth, of the School of Pharmacy Faculty Innovation Fund in 2016. He received this award again, with Dr. Edward Kelly, in 2020.

Recent Publications

High-throughput analysis of lipidomic phenotypes of methicillin-resistant Staphylococcus aureus by coupling in situ 96-well cultivation and HILIC-ion mobility-mass spectrometry. Zhang R, Ashford NK, Li A, Ross DH, Werth BJ, Xu L. Anal Bioanal Chem. 2023 Aug 3. doi: 10.1007/s00216-023-04890-6. Online ahead of print.

Elucidating the Impact of Bacterial Lipases, Human Serum Albumin, and FASII Inhibition on the Utilization of Exogenous Fatty Acids by Staphylococcus aureus. Pruitt EL, Zhang R, Ross DH, Ashford NK, Chen X, Alonzo F, Bush MF, Werth BJ, Xu L. bioRxiv. 2023 Jun 30:2023.06.29.547085. doi: 10.1101/2023.06.29.547085. Preprint.

Tracking the Metabolic Fate of Exogenous Arachidonic Acid in Ferroptosis Using Dual-Isotope Labeling Lipidomics Reimers N, Do Q, Zhang R, Guo A, Ostrander R, Shoji A, Vuong C, Xu L bioRxiv 2023.05.28.542640; doi: https://doi.org/10.1101/2023.05.28.542640 [Preprint]

Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern. Arnold WA, Blum A, Branyan J, Bruton TA, Carignan CC, Cortopassi G, Datta S, DeWitt J, Doherty AC, Halden RU, Harari H, Hartmann EM, Hrubec TC, Iyer S, Kwiatkowski CF, LaPier J, Li D, Li L, Muñiz Ortiz JG, Salamova A, Schettler T, Seguin RP, Soehl A, Sutton R, Xu L, Zheng G. Environ Sci Technol. 2023 May 23;57(20):7645-7665. doi: 10.1021/acs.est.2c08244. Epub 2023 May 8.

Differential Contributions of Distinct Free Radical Peroxidation Mechanisms to the Induction of Ferroptosis. Do Q, Zhang R, Hooper G, Xu L. JACS Au. 2023 Mar 4;3(4):1100-1117. doi: 10.1021/jacsau.2c00681. eCollection 2023 Apr 24.

7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome. Tomita H, Hines KM, Herron JM, Li A, Baggett DW, Xu L. Elife. 2022 Sep 16;11:e67141. doi: 10.7554/eLife.67141. Online ahead of print.

High-Throughput Measurement and Machine Learning-Based Prediction of Collision Cross Sections for Drugs and Drug Metabolites. Ross DH, Seguin RP, Krinsky AM, Xu L. J Am Soc Mass Spectrom. 2022 Jun 1;33(6):1061-1072. doi: 10.1021/jasms.2c00111. Epub 2022 May 11.

Emergence of dalbavancin, vancomycin, and daptomycin non-susceptible Staphylococcus aureus in a patient treated with dalbavancin: Case report and isolate characterization. Zhang R, Polenakovik H, Barreras Beltran IA, Waalkes A, Salipante SJ, Xu L, Werth BJ. Clin Infect Dis. 2022 May 1:ciac341. doi: 10.1093/cid/ciac341. Online ahead of print.

CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids. Lo M, Sharir A, Paul MD, Torosyan H, Agnew C, Li A, Neben C, Marangoni P, Xu L, Raleigh DR, Jura N, Klein OD. Nat Commun. 2022 May 3;13(1):2407. doi: 10.1038/s41467-022-30186-x.

Evolution of Enterococcus faecium in Response to a Combination of Daptomycin and Fosfomycin Reveals Distinct and Diverse Adaptive Strategies. Supandy A, Mehta HH, Tran TT, Miller WR, Zhang R, Xu L, Arias CA, Shamoo Y. Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0233321. doi: 10.1128/aac.02333-21. Epub 2022 May 11.

Temporal changes in the brain lipidome during neurodevelopment of Smith-Lemli-Opitz syndrome mice. Li A, Hines KM, Ross DH, MacDonald JW, Xu L. Analyst. 2022 Apr 11;147(8):1611-1621. doi: 10.1039/d2an00137c.

Discovery of coordinately regulated pathways that provide innate protection against interbacterial antagonism. Ting SY, LaCourse KD, Ledvina HE, Zhang R, Radey MC, Kulasekara HD, Somavanshi R, Bertolli SK, Gallagher LA, Kim J, Penewit KM, Salipante SJ, Xu L, Peterson SB, Mougous JD. Elife. 2022 Feb 17;11:e74658. doi: 10.7554/eLife.74658.

Synergy Between Beta-Lactams and Lipo-, Glyco-, and Lipoglycopeptides, Is Independent of the Seesaw Effect in Methicillin-Resistant Staphylococcus aureus. Zhang R, Barreras Beltran IA, Ashford NK, Penewit K, Waalkes A, Holmes EA, Hines KM, Salipante SJ, Xu L, Werth BJ. Front Mol Biosci. 2021 Sep 9;8:688357. doi: 10.3389/fmolb.2021.688357. eCollection 2021.

Varied Contribution of Phospholipid Shedding From Membrane to Daptomycin Tolerance in Staphylococcus aureus. Shen T, Hines KM, Ashford NK, Werth BJ, Xu L. Front Mol Biosci. 2021 Jun 11;8:679949. doi: 10.3389/fmolb.2021.679949. eCollection 2021.

Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposure. Hrubec TC, Seguin RP, Xu L, Cortopassi GA, Datta S, Hanlon AL, Lozano AJ, McDonald VA, Healy CA, Anderson TC, Musse NA, Williams RT. Toxicol Rep. 2021 Mar 9;8:646-656. doi: 10.1016/j.toxrep.2021.03.006. eCollection 2021.

Determination of drugs and drug metabolites by ion mobility-mass spectrometry: A review. Ross DH, Xu L. Anal Chim Acta. 2021 Apr 15;1154:338270. doi: 10.1016/j.aca.2021.338270. Epub 2021 Feb 2.

Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome. Pfeffer BA, Xu L, Fliesler SJ. Int J Mol Sci. 2021 Feb 26;22(5):2339. doi: 10.3390/ijms22052339.

Smoothened-activating lipids drive resistance to CDK4/6 inhibition in Hedgehog-associated medulloblastoma cells and preclinical models. Daggubati V, Hochstelter J, Bommireddy A, Choudhury A, Krup AL, Kaur P, Tong P, Li A, Xu L, Reiter JF, Raleigh DR. J Clin Invest. 2021 Mar 15;131(6):e141171. doi: 10.1172/JCI141171.

Dalbavancin exposure in vitro selects for dalbavancin-non-susceptible and vancomycin-intermediate strains of methicillin-resistant Staphylococcus aureus. Werth BJ, Ashford NK, Penewit K, Waalkes A, Holmes EA, Ross DH, Shen T, Hines KM, Salipante SJ, Xu L. Clin Microbiol Infect. 2021 Jun; 27(6):910.e1-910.e8. doi: 10.1016/j.cmi.2020.08.025. Epub 2020 Aug 28.

Benzalkonium Chloride Disinfectants Induce Apoptosis, Inhibit Proliferation, and Activate the Integrated Stress Response in a 3-D in Vitro Model of Neurodevelopment. Herron JM, Tomita H, White CC, Kavanagh TJ, Xu L. Chem Res Toxicol. 2021 May 17;34(5):1265-1274. doi: 10.1021/acs.chemrestox.0c00386. Epub 2021 Jan 20.

Determination of drugs and drug metabolites by ion mobility-mass spectrometry: A review. Ross DH, Xu L. Anal Chim Acta. 2021 Apr 15;1154:338270. doi: 10.1016/j.aca.2021.338270. Epub 2021 Feb 2.

Sterol and oxysterol synthases near the ciliary base activate the Hedgehog pathway. Findakly S, Daggubati V, Garcia G, LaStella SA, Choudhury A, Tran C, Li A, Tong P, Garcia JQ, Puri N, Reiter JF, Xu L, Raleigh DR. J Cell Biol. 2021 Jan 4;220(1):e202002026. doi: 10.1083/jcb.202002026.

Development and Application of a Peroxyl Radical Clock Approach for Measuring Both Hydrogen-Atom Transfer and Peroxyl Radical Addition Rate Constants. Do Q, Lee DD, Dinh AN, Seguin RP, Zhang R, Xu L. J Org Chem. 2021 Jan 1;86(1):153-168. doi: 10.1021/acs.joc.0c01920. Epub 2020 Dec 3.

Identification of a novel tedizolid resistance mutation in rpoB of MRSA after in vitro serial passage. Shen T, Penewit K, Waalkes A, Xu L, Salipante SJ, Nath A, Werth BJ. J Antimicrob Chemother. 2021 Jan 19;76(2):292-296. doi: 10.1093/jac/dkaa422.

Quaternary Ammonium Compound Disinfectants Reduce Lupus-Associated Splenomegaly by Targeting Neutrophil Migration and T-Cell Fate. Abdelhamid L, Cabana-Puig X, Mu Q, Moarefian M, Swartwout B, Eden K, Das P, Seguin RP, Xu L, Lowen S, Lavani M, Hrubec TC, Jones CN, Luo XM. Front Immunol. 2020 Oct 21;11:575179. doi: 10.3389/fimmu.2020.575179. eCollection 2020.

LiPydomics: A Python Package for Comprehensive Prediction of Lipid Collision Cross Sections and Retention Times and Analysis of Ion Mobility-Mass Spectrometry-Based Lipidomics Data. Ross DH, Cho JH, Zhang R, Hines KM, Xu L. Anal Chem. 2020 Nov 17;92(22):14967-14975. doi: 10.1021/acs.analchem.0c02560. Epub 2020 Oct 29.

Lipidomic and Ultrastructural Characterization of the Cell Envelope of Staphylococcus aureus Grown in the Presence of Human Serum. Hines KM, Alvarado G, Chen X, Gatto C, Pokorny A, Alonzo F 3rd, Wilkinson BJ, Xu L. mSphere. 2020 Jun 17;5(3):e00339-20. doi: 10.1128/mSphere.00339-20.

Resistome of Staphylococcus aureus in Response to Human Cathelicidin LL-37 and Its Engineered Antimicrobial Peptides. Golla RM, Mishra B, Dang X, Lakshmaiah Narayana J, Li A, Xu L, Wang G. ACS Infect Dis. 2020 Jul 10;6(7):1866-1881. doi: 10.1021/acsinfecdis.0c00112. Epub 2020 May 11.

Breaking Down Structural Diversity for Comprehensive Prediction of Ion-Neutral Collision Cross Sections. Ross DH, Cho JH, Xu L. Anal Chem. 2020 Mar 17;92(6):4548-4557. doi: 10.1021/acs.analchem.9b05772. Epub 2020 Mar 6.

Occurrence of cross-resistance and β-lactam seesaw effect in glycopeptide-, lipopeptide- and lipoglycopeptide-resistant MRSA correlates with membrane phosphatidylglycerol levels. Hines KM, Shen T, Ashford NK, Waalkes A, Penewit K, Holmes EA, McLean K, Salipante SJ, Werth BJ, Xu L. J Antimicrob Chemother. 2020 May 1;75(5):1182-1186. doi: 10.1093/jac/dkz562.