team: Department of Medicinal Chemistry

Accepting Students to Lab: Yes

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

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

Examining the Nephrotoxicity Induced by Benzalkonium Chlorides in 2D and 3D-Cultured Human Proximal Tubule Epithelial Cells Brzoska M, Seguin RP, Yang J, Kelly E, Xu L. J Pharmacol Exp Ther. 2025 Mar, Volume 392, Issue 3, DOI: 10.1016/j.jpet.2024.101674

Respective Roles of CYP4F2 and CYP2D6 in the Formation of Even- and Odd-Carbon Carboxylic Acid Metabolites of Benzalkonium Chloride in Human Hepatocytes  Zhu L, Seguin RP, Xu L. J Pharmacol Exp Ther. 2025 Mar, Volume 392, Issue 3, DOI: 10.1016/j.jpet.2024.101708

Interaction of Benzalkonium Chlorides with CYP168A1 of Pseudomonas aeruginosa Seguin RP, Kandel SE, Lampe JN, Xu L. J Pharmacol Exp Ther. 2025 Mar, Volume 392, Issue 3, DOI: 10.1016/j.jpet.2025.103508

A Multidimensional Database for Biomonitoring of Quaternary Ammonium Compounds and Their Phase I Metabolites in Human Feces Nguyen R, Liu X, Liem L, Lin YS, Xu L. J Pharmacol Exp Ther. 2025 Mar, Volume 392, Issue 3, DOI: 10.1016/j.jpet.2024.101672

PubChemLite Plus Collision Cross Section (CCS) Values for Enhanced Interpretation of Nontarget Environmental Data. Elapavalore A, Ross DH, Grouès V, Aurich D, Krinsky AM, Kim S, Thiessen PA, Zhang J, Dodds JN, Baker ES, Bolton EE, Xu L, Schymanski EL. Environ Sci Technol Lett. 2025 Jan 24;12(2):166-174.

Simulated exposures of oritavancin in in vitro pharmacodynamic models select for methicillin-resistant Staphylococcus aureus with reduced susceptibility to oritavancin but minimal cross-resistance or seesaw effect with other antimicrobials. Werth BJ, Zhang R, Barreras Beltran IA, Penewit K, Waalkes A, Holmes EA, Salipante SJ, Xu L. J Antimicrob Chemother. 2025 Feb 12:dkaf042.

Growth of Staphylococcus aureus in the presence of oleic acid shifts the glycolipid fatty acid profile and increases resistance to antimicrobial peptides. Raskovic D, Alvarado G, Hines KM, Xu L, Gatto C, Wilkinson BJ, Pokorny A. Biochim Biophys Acta Biomembr. 2025 Jan;1867(1):184395.

Empirically establishing drug exposure records directly from untargeted metabolomics data. Zhao HN, Kvitne KE, … Xu L, Knight R, Tsunoda SM, Dorrestein PC. bioRxiv [Preprint]. 2024 Oct 26:2024.10.07.617109.

Molecular basis of cell membrane adaptation in daptomycin-resistant Enterococcus faecalis. Nguyen AH, Tran TT, Panesso D, Hood KS, Polamraju V, Zhang R, Khan A, Miller WR, Mileykovskaya E, Shamoo Y, Xu L, Vitrac H, Arias CA. JCI Insight. 2024 Nov 22;9(22):e173836.

Oral exposure to benzalkonium chlorides in male and female mice reveals alteration of the gut microbiome and bile acid profile. Lopez VA, Lim JJ, Seguin RP, Dempsey JL, Kunzman G, Cui JY, Xu L. Toxicol Sci. 2024 Dec 1;202(2):265-277.

Acetyl-CoA carboxylase inhibition increases retinal pigment epithelial cell fatty acid flux and restricts apolipoprotein efflux. Hass DT, Pandey K, Engel A, Horton N, Haydinger CD, Robbings BM, Lim RR, Sadilek M, Zhang Q, Gulette GA, Li A, Xu L, Miller JML, Chao JR, Hurley JB. J Biol Chem. 2024 Oct;300(10):107772.

Several common methods of making vesicles (except an emulsion method) capture intended lipid ratios. Weakly HMJ, Wilson KJ, Goetz GJ, Pruitt EL, Li A, Xu L, Keller SL. Biophys J. 2024 Oct 1;123(19):3452-3462.

Erratum: How do different lipid peroxidation mechanisms contribute to ferroptosis? Do Q, Xu L. Cell Rep Phys Sci. 2024 May 15;5(5):101932.

Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis. Miller WR, Nguyen A, Singh KV, Rizvi S, Khan A, Erickson SG, Egge SL, Cruz M, Dinh AQ, Diaz L, Thornton PC, Zhang R, Xu L, Garsin DA, Shamoo Y, Arias CA. J Infect Dis. 2024 Apr 5:jiae173.

Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans. Nguyen R, Seguin RP, Ross DH, Chen P, Richardson S, Liem J, Lin YS, Xu L. Environ Sci Technol. 2024 Apr 9;58(14):6236-6249.

How do different lipid peroxidation mechanisms contribute to ferroptosis? Do Q, Xu L. Cell Rep Phys Sci. 2023 Dec 20;4(12):101683.

Interaction and Transport of Benzalkonium Chlorides by the Organic Cation and Multidrug and Toxin Extrusion Transporters. Vieira LS, Seguin RP, Xu L, Wang J. Drug Metab Dispos. 2024 Mar 13;52(4):312-321.

Cholic acid increases plasma cholesterol in Smith-Lemli-Opitz syndrome: A pilot study. Elias ER, Orth LE, Li A, Xu L, Jones SM, Rizzo WB. Mol Genet Metab Rep. 2023 Nov 28;38:101030.

Temporal gene expression changes and affected pathways in neurodevelopment of a mouse model of Smith-Lemli-Opitz syndrome. Li A, Tomita H, Xu L. bioRxiv. 2023 Nov 21:2023.11.21.568116.

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 3rd, Bush MF, Werth BJ, Xu L. mSphere. 2023 Dec 20;8(6):e0036823.

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 Oct;415(25):6191-6199.

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;

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.

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.

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.

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.

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.

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.

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.

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.

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.