Wenhan Zhu, Ph.D.

Assistant Professor

wenhan.zhu.1@vanderbilt.edu
Faculty Appointments
Assistant Professor of Pathology, Microbiology and Immunology
Education
Ph.D., Biological Sciences, Purdue University, West Lafayette, IndianaB.Sc., Biotechnology, Sun Yat-Sen University, Guangzhou, China
Office Address
1161 21st Ave
Nashville, TN 37232
Research Description
In our lab, we focus on the metabolic interactions that dictate the changes or resilience of the microbiota. Insight into such interactions would enable precise manipulation of gut microbiota composition, thus restoring a balanced community in situ and improving host health. To precisely manipulate the microbiota, we use a multidisciplinary discovery pipeline that consists of next-generation sequencing, cutting-edge proteomics and metabolomics, bacterial genetics, and a mechanistic understanding of bacterial physiology in vivo. This pipeline allows us to discover druggable targets of the microbiota and translate our findings using high-throughput screening. Moreover, we investigate how carcinogenic bacterial pathogen rewires host metabolism to feeds its metabolic needs to colonize the host and cause diseases. This will lay the foundation for precision editing strategies that remove the carcinogenic pathogen but preserves the rest of the microbiota.feed
Research Keywords
Resilience, commensal bacteria, microbiota, inflammation, precision editing, rational engineering, cancer, carcinogenic bacteria, nutritional immunity, anaerobic bacteria
Publications
Spiga L, Fansler RT, Perera YR, Shealy NG, Munneke MJ, Torres TP, David HE, Lemoff A, Ran X, Richardson KL, Pudlo N, Martens EC, Yang ZJ, Skaar EP, Byndloss MX, Chazin WJ, Zhu W. Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection. BioRxiv. 2023 Jun 6/26/2023; PMID: 37425782, PMCID: PMC10326984, PII: 2023.06.25.546471, DOI: 10.1101/2023.06.25.546471.

Fansler RT, Spiga L, Langford M, Zhu W. Respire or expire-precision killing of Helicobacter pylori by targeting complex I respiration. Cell Chem Biol. 2023 May 5/18/2023; 30(5): 417-9. PMID: 37207630, PII: S2451-9456(23)00122-8, DOI: 10.1016/j.chembiol.2023.04.015, ISSN: 2451-9448.

Bessho S, Grando KCM, Kyrylchuk K, Miller A, Klein-Szanto AJ, Zhu W, Gallucci S, Tam V, Tükel Ç. Systemic exposure to bacterial amyloid curli alters the gut mucosal immune response and the microbiome, exacerbating Salmonella-induced arthritis. Gut Microbes. 2023; 15(1): 2221813. PMID: 37317012, PMCID: PMC10269392, DOI: 10.1080/19490976.2023.2221813, ISSN: 1949-0984.

Taylor SJ, Winter MG, Gillis CC, Silva LAD, Dobbins AL, Muramatsu MK, Jimenez AG, Chanin RB, Spiga L, Llano EM, Rojas VK, Kim J, Santos RL, Zhu W, Winter SE. Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis. Microbiome. 2022 Nov 11/26/2022; 10(1): 200. PMID: 36434690, PMCID: PMC9701030, PII: 10.1186/s40168-022-01389-7, DOI: 10.1186/s40168-022-01389-7, ISSN: 2049-2618.

Fansler RT, Zhu W. Mind the Gap: Bridging the Divide from Sequencing Data to Empiric Phenotypes in the Human Gut Microbiota. MSystems [print-electronic]. 2022 Jun 6/28/2022; 7(3): e0020722. PMID: 35695430, PMCID: PMC9239041, DOI: 10.1128/msystems.00207-22, ISSN: 2379-5077.

Hughes ER, Winter MG, Alves da Silva L, Muramatsu MK, Jimenez AG, Gillis CC, Spiga L, Chanin RB, Santos RL, Zhu W, Winter SE. Reshaping of bacterial molecular hydrogen metabolism contributes to the outgrowth of commensal E. coli during gut inflammation. Elife. 2021 Jun 6/4/2021; 10: PMID: 34085924, PMCID: PMC8177889, PII: 58609, DOI: 10.7554/eLife.58609, ISSN: 2050-084X.

Chanin RB, Winter MG, Spiga L, Hughes ER, Zhu W, Taylor SJ, Arenales A, Gillis CC, Büttner L, Jimenez AG, Smoot MP, Santos RL, Winter SE. Epithelial-Derived Reactive Oxygen Species Enable AppBCX-Mediated Aerobic Respiration of Escherichia coli during Intestinal Inflammation. Cell Host Microbe [print-electronic]. 2020 Dec 12/9/2020; 28(6): 780-788.e5. PMID: 33053375, PMCID: PMC7736183, PII: S1931-3128(20)30506-0, DOI: 10.1016/j.chom.2020.09.005, ISSN: 1934-6069.

Ellermann M, Pacheco AR, Jimenez AG, Russell RM, Cuesta S, Kumar A, Zhu W, Vale G, Martin SA, Raj P, McDonald JG, Winter SE, Sperandio V. Endocannabinoids Inhibit the Induction of Virulence in Enteric Pathogens. Cell [print-electronic]. 2020 Oct 10/29/2020; 183(3): 650-665.e15. PMID: 33031742, PMCID: PMC7606741, PII: S0092-8674(20)31163-6, DOI: 10.1016/j.cell.2020.09.022, ISSN: 1097-4172.

Menezes-Garcia Z, Kumar A, Zhu W, Winter SE, Sperandio V. L-Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens. Proc Natl Acad Sci U S A [print-electronic]. 2020 Jun 6/2/2020; 117(22): 12387-93. PMID: 32409599, PMCID: PMC7275701, PII: 1919683117, DOI: 10.1073/pnas.1919683117, ISSN: 1091-6490.

Zhu W, Winter MG, Spiga L, Hughes ER, Chanin R, Mulgaonkar A, Pennington J, Maas M, Behrendt CL, Kim J, Sun X, Beiting DP, Hooper LV, Winter SE. Xenosiderophore Utilization Promotes Bacteroides thetaiotaomicron Resilience during Colitis. Cell Host Microbe [print-electronic]. 2020 Mar 3/11/2020; 27(3): 376-388.e8. PMID: 32075741, PMCID: PMC7439322, PII: S1931-3128(20)30049-4, DOI: 10.1016/j.chom.2020.01.010, ISSN: 1934-6069.

Zhu W, Miyata N, Winter MG, Arenales A, Hughes ER, Spiga L, Kim J, Sifuentes-Dominguez L, Starokadomskyy P, Gopal P, Byndloss MX, Santos RL, Burstein E, Winter SE. Editing of the gut microbiota reduces carcinogenesis in mouse models of colitis-associated colorectal cancer. J Exp Med [print-electronic]. 2019 Oct 10/7/2019; 216(10): 2378-93. PMID: 31358565, PMCID: PMC6781011, PII: jem.20181939, DOI: 10.1084/jem.20181939, ISSN: 1540-9538.

Wilson RP, Tursi SA, Rapsinski GJ, Medeiros NJ, Le LS, Kotredes KP, Patel S, Liverani E, Sun S, Zhu W, Kilpatrick L, Winter SE, Gamero AM, Tükel Ç. STAT2 dependent Type I Interferon response promotes dysbiosis and luminal expansion of the enteric pathogen Salmonella Typhimurium. PLoS Pathog. 2019 Apr; 15(4): e1007745. PMID: 31009517, PMCID: PMC6513112, PII: PPATHOGENS-D-18-01529, DOI: 10.1371/journal.ppat.1007745, ISSN: 1553-7374.

Gillis CC, Winter MG, Chanin RB, Zhu W, Spiga L, Winter SE. Host-Derived Metabolites Modulate Transcription of Salmonella Genes Involved in l-Lactate Utilization during Gut Colonization. Infect Immun [electronic-print]. 2019 Apr; 87(4): PMID: 30617205, PMCID: PMC6434127, PII: IAI.00773-18, DOI: 10.1128/IAI.00773-18, ISSN: 1098-5522.

Duerkop BA, Kleiner M, Paez-Espino D, Zhu W, Bushnell B, Hassell B, Winter SE, Kyrpides NC, Hooper LV. Murine colitis reveals a disease-associated bacteriophage community. Nat Microbiol [print-electronic]. 2018 Sep; 3(9): 1023-31. PMID: 30038310, PMCID: PMC6112176, PII: 10.1038/s41564-018-0210-y, DOI: 10.1038/s41564-018-0210-y, ISSN: 2058-5276.

Miyata N, Morris LL, Chen Q, Thorne C, Singla A, Zhu W, Winter M, Melton SD, Li H, Sifuentes-Dominguez L, Llano E, Huff-Hardy K, Starokadomskyy P, Lopez A, Reese TA, Turer E, Billadeau DD, Winter SE, Burstein E. Microbial Sensing by Intestinal Myeloid Cells Controls Carcinogenesis and Epithelial Differentiation. Cell Rep. 2018 Aug 8/28/2018; 24(9): 2342-55. PMID: 30157428, PMCID: PMC6177233, PII: S2211-1247(18)31184-7, DOI: 10.1016/j.celrep.2018.07.066, ISSN: 2211-1247.

Gillis CC, Hughes ER, Spiga L, Winter MG, Zhu W, Furtado de Carvalho T, Chanin RB, Behrendt CL, Hooper LV, Santos RL, Winter SE. Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth. Cell Host Microbe. 2018 Apr 4/11/2018; 23(4): 570. PMID: 29649446, PMCID: PMC5907491, PII: S1931-3128(18)30142-2, DOI: 10.1016/j.chom.2018.03.013, ISSN: 1934-6069.

Zhu W, Winter MG, Byndloss MX, Spiga L, Duerkop BA, Hughes ER, Büttner L, de Lima Romão E, Behrendt CL, Lopez CA, Sifuentes-Dominguez L, Huff-Hardy K, Wilson RP, Gillis CC, Tükel Ç, Koh AY, Burstein E, Hooper LV, Bäumler AJ, Winter SE. Precision editing of the gut microbiota ameliorates colitis. Nature [print-electronic]. 2018 Jan 1/11/2018; 553(7687): 208-11. PMID: 29323293, PMCID: PMC5804340, PII: nature25172, DOI: 10.1038/nature25172, ISSN: 1476-4687.

Gillis CC, Hughes ER, Spiga L, Winter MG, Zhu W, Furtado de Carvalho T, Chanin RB, Behrendt CL, Hooper LV, Santos RL, Winter SE. Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth. Cell Host Microbe [print-electronic]. 2018 Jan 1/10/2018; 23(1): 54-64.e6. PMID: 29276172, PMCID: PMC5764812, PII: S1931-3128(17)30500-0, DOI: 10.1016/j.chom.2017.11.006, ISSN: 1934-6069.

Spiga L, Winter MG, Furtado de Carvalho T, Zhu W, Hughes ER, Gillis CC, Behrendt CL, Kim J, Chessa D, Andrews-Polymenis HL, Beiting DP, Santos RL, Hooper LV, Winter SE. An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate. Cell Host Microbe [print-electronic]. 2017 Sep 9/13/2017; 22(3): 291-301.e6. PMID: 28844888, PMCID: PMC5599368, PII: S1931-3128(17)30301-3, DOI: 10.1016/j.chom.2017.07.018, ISSN: 1934-6069.

Hughes ER, Winter MG, Duerkop BA, Spiga L, Furtado de Carvalho T, Zhu W, Gillis CC, Büttner L, Smoot MP, Behrendt CL, Cherry S, Santos RL, Hooper LV, Winter SE. Microbial Respiration and Formate Oxidation as Metabolic Signatures of Inflammation-Associated Dysbiosis. Cell Host Microbe. 2017 Feb 2/8/2017; 21(2): 208-19. PMID: 28182951, PMCID: PMC5313043, PII: S1931-3128(17)30027-6, DOI: 10.1016/j.chom.2017.01.005, ISSN: 1934-6069.

Liu Y, Zhu W, Tan Y, Nakayasu ES, Staiger CJ, Luo ZQ. A Legionella Effector Disrupts Host Cytoskeletal Structure by Cleaving Actin. PLoS Pathog. 2017 Jan; 13(1): e1006186. PMID: 28129393, PMCID: PMC5298343, PII: PPATHOGENS-D-16-00655, DOI: 10.1371/journal.ppat.1006186, ISSN: 1553-7374.

Zhu W, Luo ZQ. Cell biology and immunology lessons taught by Legionella pneumophila. Sci China Life Sci [print-electronic]. 2016 Jan; 59(1): 3-10. PMID: 26596966, PII: 10.1007/s11427-015-4945-x, DOI: 10.1007/s11427-015-4945-x, ISSN: 1869-1889.

Wang T, Si M, Song Y, Zhu W, Gao F, Wang Y, Zhang L, Zhang W, Wei G, Luo ZQ, Shen X. Type VI Secretion System Transports Zn2+ to Combat Multiple Stresses and Host Immunity. PLoS Pathog. 2015 Jul; 11(7): e1005020. PMID: 26134274, PMCID: PMC4489752, PII: PPATHOGENS-D-14-02456, DOI: 10.1371/journal.ppat.1005020, ISSN: 1553-7374.

Zhu W, Luo ZQ. A new way to detect the danger: Lysosomal cell death induced by a bacterial ribosomal protein. J Nat Sci. 2015 Jun; 1(6): PMID: 26052550, PMCID: PMC4457467, ISSN: 2377-2700.

Zhu W, Tao L, Quick ML, Joyce JA, Qu JM, Luo ZQ. Sensing cytosolic RpsL by macrophages induces lysosomal cell death and termination of bacterial infection. PLoS Pathog. 2015 Mar; 11(3): e1004704. PMID: 25738962, PMCID: PMC4349785, PII: PPATHOGENS-D-14-02610, DOI: 10.1371/journal.ppat.1004704, ISSN: 1553-7374.

Zhu W, Hammad LA, Hsu F, Mao Y, Luo ZQ. Induction of caspase 3 activation by multiple Legionella pneumophila Dot/Icm substrates. Cell Microbiol [print-electronic]. 2013 Nov; 15(11): 1783-95. PMID: 23773455, PMCID: PMC3797225, DOI: 10.1111/cmi.12157, ISSN: 1462-5822.

Tao L, Zhu W, Hu BJ, Qu JM, Luo ZQ. Induction of rapid cell death by an environmental isolate of Legionella pneumophila in mouse macrophages. Infect Immun [print-electronic]. 2013 Sep; 81(9): 3077-88. PMID: 23753633, PMCID: PMC3754228, PII: IAI.00252-13, DOI: 10.1128/IAI.00252-13, ISSN: 1098-5522.

Zhu W, Luo ZQ. Methods for determining protein translocation by the Legionella pneumophila Dot/Icm type IV secretion system. Methods Mol Biol. 2013; 954: 323-32. PMID: 23150405, DOI: 10.1007/978-1-62703-161-5_19, ISSN: 1940-6029.

Hsu F, Zhu W, Brennan L, Tao L, Luo ZQ, Mao Y. Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase. Proc Natl Acad Sci U S A [print-electronic]. 2012 Aug 8/21/2012; 109(34): 13567-72. PMID: 22872863, PMCID: PMC3427105, PII: 1207903109, DOI: 10.1073/pnas.1207903109, ISSN: 1091-6490.

Zhu W, Banga S, Tan Y, Zheng C, Stephenson R, Gately J, Luo ZQ. Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila. PLoS One. 2011 Mar 3/9/2011; 6(3): e17638. PMID: 21408005, PMCID: PMC3052360, DOI: 10.1371/journal.pone.0017638, ISSN: 1932-6203.

Du L, Su Y, Sun D, Zhu W, Wang J, Zhuang X, Zhou S, Lu Y. Formic acid induces Yca1p-independent apoptosis-like cell death in the yeast Saccharomyces cerevisiae. FEMS Yeast Res [print-electronic]. 2008 Jun; 8(4): 531-9. PMID: 18452540, PII: FYR375, DOI: 10.1111/j.1567-1364.2008.00375.x, ISSN: 1567-1356.