The Wu lab investigates fundamental mechanisms of respiratory infection and host immune defense to help discover new regulators of disease pathogenesis and progression, ultimately revealing new targets for effective therapy of some horrible superbugs’ infection. Considering bacterial virulence and pathogenesis, the lab asks how CRISPR-Cas adaptive immune systems regulate pathogen endogenous gene expression to dictate bacterial invasion and alter the host defense using a combination approach (cell biology, advanced microscopy, negative genetics, and RNA-seq). The long-term goal is to develop novel therapeutic strategies (e.g., antimicrobial compounds, peptides, and gene delivery) and vaccines (e.g., attenuated bacterial strains) that target to our newly identified signal pathways using new nanoparticles in diagnostics, imaging, and therapy. 

• Lin P, Pu Q, Wu Q, Zhou C, Wang B, Schettler J, Wang Z, Qin S, Gao P, Li G, Lan L, Jiang J, and Wu M.  High-throughput screen reveals sRNAs that regulate crRNA biogenesis by targeting CRISPR leader to repress Rho termination. Nat Commun 2019; Aug 19;10(1):3728. doi: 10.1038/s41467-019-11695-8.
• Zhang Y, Zhou C, Pu Q, Tan S, Shao X, Shi H, Li R, Weiland T, Yu X, Wu M, and Deng X. Pseudomonas aeruginosa regulatory protein AnvM controls pathogenicity in anaerobic environment and impacts host defense mBio 2019 Jul 23;10(4). pii: e01362-19. doi: 10.1128/mBio.01362-19 (Corresponding author).  
• Wang Z, Pu Q, Huang C, Li C, Jiang X and Wu M. Design of Cecal Ligation and Puncture (CLP) and Intranasal Infection Dual Model of Sepsis-induced Immunosuppression. J of Video Experiments 2019 Jun 15;(148). doi: 10.3791/59386.
• Lin P, Shen G, Pu Q, Li R, Yang X, Zhou C, Liang H, Jiang J, and Wu M. CdpR inhibits CRISPR-Cas to lower anti-viral adaptive immunity while avoiding self-reactivity. iScience 2019;13:55-68 (Corresponding author).
• Chin W*, Zhong G*, Pu Q*, Yang C, Lou W, Florez De Sessions P, Periaswamy B, Liang ZC, Gao S, Chu CW, Bianco S, Bao C, Ding X, Tong YW, Fan W, Wu M$, Hedick J$, Yang YY$. A macromolecular therapeutic approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset. Nat Communications 2018;9:917 http://rdcu.be/H9rX ($Co-corresponding author; * co-first authors). 
• Li R, Yu M, Li X, He S, Weiland T, Bansal A, Jiang J and Wu M. Long noncoding RNA MEG3-4 is a tissue specific regulator of IL-1b in pulmonary infection by repressing micoRNA-138.  Li R, Fang L, Yu M, Li X, Pu Q, Weiland T, Bansal A, Ye SQ, Jiang J and Wu M. Long noncoding RNA MEG3-4 is a tissue specific regulator of IL-1b in pulmonary infection by repressing micoRNA-138. Science Signaling Jun 26 2018;11(536). pii: eaao2387. doi: 10.1126/scisignal.aao2387.

• Li R, Tan S, Yu M, Li X, He S, Wei Y, and Wu M. Pseudomonas aeruginosa evades host immunity by Type I CRISPR-Cas mediated endogenous targeting. Cell Research 2016;26(12):1273-1287. doi: 10.1038/cr.2016.135. (with accompany research highlight paper and cover image). http://www.nature.com/cr/journal/v26/n12/full/cr2016135a.html

• Li X, He S, Ye Y, Zhou X, Tan S, Jundt M.C., Lenz C, Lichter N, Hidebrand A, Wang Y, Li G, Huang C, and Wu M. Lyn delivers bacterial substance to lysosomes for eradication through TLR-2-initiated and autophagy-mediated phagocytosis. PLoS Pathogens 2016 Jan 6;12(1):e1005363. doi: 10.1371/journal.ppat.1005363.

• Zhao J, Yu X, Zhu M, Kang H, Ma J, Wu M, Gan J, Deng X, and Liang H. Structural and molecular mechanism of CdpR involved in quorum-sensing and bacterial virulence in Pseudomonas aeruginosa. PLOS Biol  2016 Apr 27;14(4):e1002449. doi: 10.1371/journal.pbio.1002449.

• He S, Li X, Li R, Wang K, Fang L, Wang Y, and Wu M. Annexin A2 modulates ROS and thus impacts inflammatory response via IL-17 signaling in polymicrobial sepsis mice. PLoS Pathogens Jul 7;12(7):e1005743. doi: 10.1371/journal.ppat.1005743. 

• Li X, He S, Zhou X, Li R, Zhang S, Yu M, Ye Y, Wang Y, Li G, Huang C, and Wu M. Pseudomonas aeruginosa infection augments inflammation through miR-301b repression of c-Myb-mediated immune activation and infiltration. Nature Microbiology 1, Article number: 16132 (2016), doi:10.1038/nmicrobiol.2016.132

• Li R, Tan S, Park H-Y, Jundt M.C., Zhang S, and Wu M. Annexin A2 regulates autophagy in Pseudomonas aeruginosa infection through Akt1-mTOR-ULK1/2 signaling. J Immunol 2015 195(8):3901-11. doi: 10.4049/jimmunol.1500967. http://www.jimmunol.org/content/195/8/3901

• Ye Y, Tan S, Zhou X, Li X, Jundt MC, Lenz C, Lichter N, Hidebrand A, and Wu M. Atg7 inhibits ubiquitylation of p-IkBa to regulate the inflammatory responses in host defense against bacterial infection. J Infect Dis 2015;212(11):1816-26.

• Zhou X, Privratsky B, Sun Y, Wang W, Birnbaumer L, Singh BB and Wu M. TRPC1 deficiency impairs host defense in P. aeruginosa infected mice and exacerbates inflammatory responses by regulating the JNK signaling circuit. Mol Cell Biol 2015;35(16):2729-39. pii: MCB.00256-15. http://mcb.asm.org/content/35/16/2729.long

• Li X, Zhou X, Ye Y, Lu Z, Huang C, and Wu M. Atg7 critically impacts Pseudomonas aeruginosa infection by down-regulating superoxide and up-regulating nitric oxide. J Immunol 2015;194(3):1112-21. http://www.jimmunol.org/content/194/3/1112.long

• Wei X, Shao B, He Z, Ye T, Luo M, Sang Y, Liang X, Wang W, Luo S, Yang S, Zhang S*, Gong C, Gou M, Deng H, Zhao Y, Yang H, Deng S, Zhao Y, Yang L, Qian Z, Li J, Sun X, Han J, Jiang C, Zhang S, Jiang C, Wu M, and Zhang Z. Cationic Nanocarriers Induce Cell Necrosis through Impairment of Na+/K+-ATPase and Cause Subsequent Inflammatory Response. Cell Research 2015;25(2):237-53. http://www.nature.com/cr/journal/v25/n2/full/cr20159a.html 

• Zhou X, Li X, Ye Y, Li Y, Privratsky B, Wang W, Wei Y, and Wu M. MicroRNA-302b augments host defense to bacteria by regulating inflammatory responses via feedback to the TLR/IRAK4 circuit. Nat Commun 2014;5, Article number: 3619, doi:10.1038/ncomms4619. (Corresponding author). Press reléase and various coverage http://www.med.und.edu/news/2014/04/und-scientists-try-to-turn-down-the-heat.cfm. Selected by F1000Prime - special significance in its field by F1000 Faculty. http://f1000.com/prime/718345439

• Liang H, Deng X, Ye Y, Li X, and Wu M. Molecular Mechanisms of Master Regulator VqsM mediating Quorum-sensing and Antibiotic Resistance in Pseudomonas aeruginosa. Nucleic Acids Res  2014;42(16):10307-20 (Co-corresponding author) http://nar.oxfordjournals.org/content/42/16/10307.long

• Cao Q, Wang Y, Chen F, Xia Y, Lou J, Zhang X, Yang N, Sun X, Zhang Q, Zhuo C, Huang X, Deng X, Yang CG, Ye Y, Zhao J, Wu M, Lan L. A novel signal transduction pathway that modulates rhl quorum sensing and bacterial virulence in Pseudomonas aeruginosa. PLoS Pathog. 2014 Aug 8;10(8):e1004340.  http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004340.

• Ding Y, Liu X, Chen F, Di H, Xu B, Zhou L, Deng X, Wu M, Yang C, and Lan L. A metabolic sensor governing bacterial virulence in Staphylococcus aureus. Proc Nat Acad Sci USA 2014(Nov 18);111(46):E4981-90. doi: 10.1073/pnas.1411077111 http://www.pnas.org/content/111/46/E4981.long

• Deng X, Weerapana E, Ulanovskaya O, Sun F, Liang H, Ji Q, Ye Y, Fu Y, Zhou L, Li J, Zhang H, Wang C, Alvarez S, Hicks LM, Lan L, Wu M, Cravatt BF, He C. Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria. Cell Host Microbe. 2013;13(3):358-70 (most accessed for the first month, featured article in Journal). ( http://www.sciencedirect.com/science/article/pii/S193131281300070X)

• Yuan K, Xie K, Fox J III, Zeng H, Gao H, Huang C, and Wu M. Decreased Levels of miR-224 and the Passenger Strand of miR-221 Increase MBD2, Suppressing Maspin and Promoting Colorectal Tumor Growth and Metastasis in Mice. Gastroenterology  2013;145(4):853-864. PMID:23770133 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783518/

• Liu R, Li J, Xie K, Zhang T, Lei Y, Chen Y, Zhang L, Huang K, Wang K, Wu H, Wu M, Nice EC, Huang C, Wei Y. FGFR4 promotes stroma-induced epithelial to mesenchymal transition in colorectal cancer. Cancer Res 2013; 73(19):5926-5935. PMID: 23943801 (Cover image article and highlighted in the journal) http://cancerres.aacrjournals.org/content/73/19/5926.long

• Yan C1, Wu M2, Zhu M3, Cao J4, Tang H1, Johnson PF5,6, & Gao H1,6 CCAAT/Enhancer-Binding Protein-d is a critical mediator of lipopolysaccharide-induced acute lung injury. Am J Pathol 2013, 182(2):420-30. (http://www.sciencedirect.com/science/article/pii/S0002944012008073)

• Wu X, Tian F, Wang W, Chen J, Wu M and Zhao JX. Fabrication of highly fluorescent graphene quantum dots using L-glutamic acid for in vitro/in vivo imaging and sensing. J Mater Chem C Mater Opt Electron Devices 2013, 1, 4676–4684. PMID: 23997934 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755467/

• Li, G, Fox J III, Gaid M, Liu Z, Liu J, Jin Y, Gao GF, Gao H, and Wu M. Lyn inhibits house dust mite–induced airway remodeling through negative regulation of TGF-b3 and epithelial mesenchymal transition. J Immunol  2013;191:5359-5370. PMID: 24127553

• Yan C, Wu M, Cao J, Tang H, Zhu M, Johnson PF, Gao H. Critical Role for CCAAT/Enhancer-Binding Protein β in Immune Complex-Induced Acute Lung Injury.  J Immunol. 2012; 189:1480-90. (http://www.jimmunol.org/content/189/3/1480.long)

• Yuan K, Huang C, Fox J III, Laturnus D, Carlson E, Gao H, and Wu M. Autophagy plays an essential role in the clearance of P. aeruginosa by alveolar macrophages. J Cell Sci 2012; 125(Pt 2):507-15.  (http://jcs.biologists.org/content/125/2/507.long)

• Tang H, Yan C, Sarma V, Haura E, Wu M, and Gao H. An essential role for Stat3 in regulating IgG immune complex-induced lung injury. FASEB J 2011;25(12):4292-300. http://www.fasebj.org/content/25/12/4292.long

• Yuan K, Huang C, Fox J, Gaid M, Weaver A, Li G, Singh B, Gao H, and Wu M. Elevated inflammatory response in Caveolin 1 knockout mice with P. aeruginosa infection is mediated by STAT3 and NF-κB. J Biol Chem 2011;286:21814-21825. DOI:10.1074/jbc.M111.237628 http://www.jbc.org/content/286/24/21814.long

• Kannan S*, Audet A*, Huang H*, Chen L, & Wu M. Cholesterol-rich lipid membrane and Lyn are required for alveolar macrophage phagocytosis during infection. J Immunol 2008; 180:2396-2408. Link: http://www.jimmunol.org/cgi/content/full/180/4/2396

• Kannan S*, Pang H, Foster D*, Rao Z and Wu M. Human 8-oxoguanine DNA glycosylase links MAPK activation to resistance to hyperoxia in lung epithelial cells. Cell Death & Differentiation 2006;13:311-323. Link: http://www.nature.com/cdd/journal/v13/n2/pdf/4401736a.pdf

• Wu M, Hussain S, He YH, Pasula R, Smith P, and Martin WJ II. Genetically Engineered Macrophages Expressing IFN-g Restore Alveolar Immune Function in scid Mice. Proc Nat Acad Sci USA 2001; 98:14589-14594. (*Highlighted in Nature Rev Immunol 1, 2002).  Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC64726/?tool=pubmed

• Wu M, He Y, Xu Y, Kobune Y, Kelley MR, and Martin WJ II. Protection of lung cells against oxygen damages using the DNA base excision repair genes Fpg and hOgg1. Am J Respir Crit Care Med 2002;166:192-199. Link: http://ajrccm.atsjournals.org/cgi/content/full/166/2/192

Education

• MD (MBBS) 1983 Luzhou Medical School, China
• MSc Immunology 1988 Shanghai Jiao Tong University (Shanghai Second Med Univ)
• PhD Genetic & Biochemistry 1997 University of Leeds, United Kingdom

Ping Lin, PhD, Postdoc, CRISPR-Cas in infection and immunity.

Luqing Cui, BS, Visiting student, CRISPR-Cas in infection and immunity. 

Qinqin Pu, BS, Exchanging student, Host defense to bacterial infection.

Pan Gao, BS, Visiting student, Host defense to bacterial infection.

Shugang Qin, MS, Visiting student, CRISPR-Cas in infection and immunity.

Honey Kosiak, Undergraduate researcher, Ebola cell signaling in host.

Alexa Privratsky, Undergraduate researcher, Cell signaling in lung inflammation.