Host mucosal immune responses to infections and the control of inflammation.
Research Interest
The external surfaces of the body include the skin and several mucosal surfaces, such as the lining of the gut, nasal passages, airways, urinary tract, and genitals. These mucosal tissues are exposed daily to an overwhelming load of substances in the form of harmful or commensal microorganisms, allergens, food antigens, etc. The mucosal immune system recognizes these diverse antigens through the presence of a highly efficient epithelial barrier and a large population of specialized and multifaceted immune cells in a scattered and organized pattern underneath epithelial cells. To maintain a balance between the good and the bad, the mucosal immune cells and molecules are carefully regulated to promote a normal immune defense capability without the destruction of the mucosal tissues. Once the mucosal barrier and this thorough balance are disturbed, nonspecific stimulation and activation can lead to different forms of inflammation, resulting in pathological lesions and functional changes in the tissues. Chronic inflammation is generally considered as a causative factor in a variety of cancers.
The current research interests in Dr. Zhu’s laboratory are to identify novel mechanisms of immune regulation on mucosal infections, explore the pro- and anti-inflammatory signals controlling inflammations and limiting pathology in tissues, and understand how the mucosal immune system distinguishes pathogenic from non-pathogenic microbes and how pathogens evade innate and adaptive immunity. Finally, Dr. Zhu’s laboratory is also interested in translating the basic research by harnessing the mucosal immune system for developing novel mucosal vaccines against several important infectious diseases, such as Influenza virus, Respiratory Syncytial Virus (RSV), and Mycobacterium tuberculosis, and designing novel immune therapeutic strategies against lung inflammation including severe asthma.
Education
- 1997 - 2000: Postdoctoral, Immunology, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA
- 1997: Ph.D., Virology, University of Wisconsin-Madison, Madison, Wisconsin, USA
- 1987: MS, Pathology, China Agricultural University, Beijing, China.
- 1984: DVM, Veterinary Medicine, Ningxia University, Yinchuan, China.
Professional Experiences
- 2019 - present: Associate Dean and Department Chair, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, Maryland
- 2013 - present: Professor of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, Maryland
- 2017 - 2018: Acting Associate Dean and Department Chair, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, Maryland
- 2008 - 2013: Associate Professor of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, Maryland
- 2003 - 2008: Assistant Professor of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, Maryland
- 2000 - 2003, Instructor in Medicine (Junior Faculty), Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts
- 1989 - 1991: Lecturer of Veterinary Pathology, College of Veterinary Medicine, China Agricultural University, Beijing, China
- 1987 - 1989: Assistant Lecturer of Veterinary Pathology, College of Veterinary Medicine, China Agricultural University, Beijing, China
Representative Publications
- Li W, Wang T, Rajendrakumar AM, Acharya G, Miao Z, Varghese BP, Yu H, Dhakal B, LeRoith T, Karunakaran A, Tuo W, Zhu X. An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission. Nat Commun 14, 7114 (2023). https://doi.org/10.1038/s41467-023-42796-0. PMID: 36451890; PMCID: PMC9709799. (www.nature.com/articles/s41467-023-42796-0). News: UMD researchers developed a nasal vaccine that prevents COVID in preclinical studies (www.eurekalert.org/news-releases/1007123)
- Goswami R, Arya RK, Sharma S, Dutta B, Stamov DR, Zhu X, Rahaman SO. Mechanosensing by TRPV4 mediates stiffness-induced foreign body response and giant cell formation. Science Signaling. 2021 Nov 2;14(707):eabd4077. doi: 10.1126/scisignal.abd4077. (https://today.umd.edu/umd-scientists-id-molecular-culprit-in-medical-implant-rejections)
- Ochsner SP, Li W, Rajendrakumar AM, Palaniyandi S, Acharya G, Liu X, Wang G, Krammer F, Shi M, Tuo W, C. Pauza CD, Zhu X. FcRn targeted mucosal vaccination against influenza virus infection. Journal of Immunology, 2021 Sep 1;207(5):1310-1321. DOI: https://journals.aai.org/jimmunol/article/207/5/1310/234477/FcRn-Targeted-Mucosal-Vaccination-against
- Chandrasekaran P, Izadjoo S, Stimely J, Palaniyandi S, Zhu X, Tafuri W, Mosser DM. Regulatory macrophages inhibit alternative macrophage activation and attenuate pathology associated with fibrosis. Journal of Immunology. 2019 Oct 15;203(8):2130-2140.
doi: 10.4049/jimmunol.1900270 - Liu X, Palaniyandi S, Zhu I, Tang J, Li W, Wu X, Park-Ochsner S, Pauza CD, Cohen JI, Zhu X. Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor. Nature Communications. 2019; 10, 3020. https://doi.org/10.1038/s41467-019-10865-y (MedicalXpress: Old protein, new tricks: Study connects a protein to antibody immunity for the first time; GEN: Cytomegalovirus’ Immune Evasion Tactics Uncovered; The Medical News: UMD researchers connect a protein to antibody immunity for the first time).
- Goswami R, Arya R, Biswas D, Zhu X, Rahaman SO. Transient rceptor potential vanilloid 4 (TRPV4) is required for foreign body response and giant cell formation. Am J Pathol. 2019 May 20. pii: S0002-9440(19)30101-4. doi: 10.1016/j.ajpath.2019.04.016.
- Goswami R, Merth M, Sharma S, Alharbi MO, Aranda-Espinoza H, Zhu X, Rahaman SO. TRPV4 calcium-permeable channel is a novel regulator of oxidized LDL-induced macrophage foam cell formation. Free Radical Biology & Medicine. 2017; 110:142-150.
- Shubin Z, Li W, Poonia B, Ferrari G, LaBranche C, Montefiori D, Zhu X, Pauza CD. An HIV envelope gp120-Fc fusion protein elicits effector antibody responses in Rhesus Macaques. Clinical & Vaccine Immunology. 2017 Jun 5;24(6).
- Liu C, Richard K, Wiggins M, Zhu X, Conrad DH, Song W. CD23 can negatively regulate B-cell receptor signaling. Science Report. 2016; 6:25629.
- Sun D, Zhang M, Liu G, Wu H, Zhu X, Zhou H, Shi M. Real-time imaging of interactions of neutrophils with Cryptococcus neoformans demonstrates a crucial role of complement C5a-C5aR signaling. Infection Immunity. 2015; 84:216-29..
- Liu G, Xu J, Wu H, Sun D, Zhang X, Zhu X, Magez S, Shi M. IL-27 signaling is crucial for survival of mice infected with African Trypanosomes via preventing lethal effects of CD4+ T cells and IFN-γ. PLoS Pathogen. 2015; 11(7):e1005065.
- Palaniyandi S, Liu X, Periyasamy S, Ma A, Tang J, Jenkins M, Tuo W, Song W, Keegan AD, Conrad D, Zhu X. Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of allergic airway inflammation. Mucosal Immunology. 2015; 8:1262-1274. (World Biomedical Frontiers Highlight: An emerging role of epithelial CD23 in asthma development and therapy).
- Khattar SK, Palaniyandi S, Samal S, LaBranche CC, Montefiori DC, Zhu X, Samal SK. Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus. Human Vaccine & Immunotherapeutics. 2015;11:504-15.
- Seeley-Fallen MK, Liu L, Shapiro M, Onabajo OO, Palaniyandi S, Zhu X, Tan TH, Upadhyay A, Song W. Actin-binding protein 1 links B-cell antigen receptors to negative signaling pathways. Proc. Natl. Acad. Sci. (USA). 2014; 111:9881-9886.
- Miller ML, Mashayekhi M, Chen L, Zhou P, Liu X, Michelotti M, Gunn NT, Powers S, Zhu X, Evaristo C, Alegre ML, Molinero L. Basal NF-kappaB activity is essential for naïve T cell survival and IL-7Ralpha expression. Proc. Natl. Acad. Sci. (USA). 2014; 111:7397-402.
- Mitra A, Palaniyandi S, Herren CD, Zhu X, Mukhopadhyay S. Pleiotropic roles of uvrY on biofilm formation, motility and virulence in uropathogenic Escherichia coli CFT073. PLoS One. 2013;8(2):e55492.
- Palaniyandi S, Mitra A, Herren CD, Zhu X, Mukhopadhyay S. LuxS contributes to virulence in avian pathogenic Escherichia coli O78:K80:H9. Veterinary Microbiology. 2013; 166:567-575.
- Samal S, Khattar SK, Paldurai A, Palaniyandi S, Zhu X, Collins PL, Samal SK. Mutations in the cytoplasmic domain of the Newcastle disease virus fusion protein confer hyperfusogenic phenotypes modulating viral replication and pathogenicity. Journal of Virology. 2013; 87:10083-10093 (corrigendum).
- Palaniyandi S, Mitra A, Herren CD, Lockatell CV, Johnson DE, Zhu X, Mukhopadhyay S. BarA-UvrY two-component system regulates virulence of uropathogenic E. coli CFT073. PLoS One. 2012;7(2):e31348.
- Palaniyandi S, Tomei E, Li Z, Conrad D, Zhu X. CD23-mediated transcytosis of IgE and immune complexes across the polarized human respiratory epithelial cells. Journal of Immunology. 2011; 186:3484-3496. (Featured article in this issue: Aiding Allergy)
- Li Z, Palaniyandi S, Zeng R, Tuo W, Roopenian DC, Zhu X. From the Cover: Transfer of immunoglobulin G in the female genital tract by a MHC class I-related neonatal Fc receptor confers protective immunity to vaginal infections. Proc. Natl. Acad. Sci. (USA). 2011; 108:4388-4393. (Featured article in this issue: Placental immune protein helps fight vaginal infection. Editorial Commentary: FcRn-Not Just For Kids. Nature Rev. Immunol. 2011, 11:234-235).
- Liu X, Lu L, Yang Z, Palaniyandi S, Zeng R, Gao L, Mosser DM, Roopenian DC, Zhu X. FcRn-mediated presentation of immune-complexed antigen is associated with the endosomal and phagosomal acidification and antigen stability in macrophages and dendritic cells. Journal of Immunology. 2011; 186:4674-4686.
- Bai Y, Ye L, Tesar DB, Song H, Zhao D, Björkman PJ, Roopenian DC, Zhu X. Intracellular neutralization of viral infection by IgG in polarized epithelial cells is dependent on FcRn-mediated IgG transport. Proc. Natl. Acad. Sci. (USA). 2011; 108:18406-18411. (Nature SciBX 4(45), Distillery: Therapeutics -Infectious disease. 2011, 1273. The Jackson Highlight: Antibody, Tag-teamed with receptor, knocks out viral infections inside cells, 2013).
- Lu L, Palaniyandi S, Zeng R, Bai Y, Liu X, Wang Y, Pauza CD, Roopenian DC, Zhu X. A novel FcRn-targeted mucosal vaccine strategy effectively induces HIV-1 antigen-specific immune responses and protection. Journal of Virology. 2011; 85:10542-10553. (The Jackson Highlight: The FcRn-mediated HIV mucosal vaccine works in mice).
- Ye L, Zeng R, Bai Y, Roopenian DC, Zhu X. Efficient mucosal vaccination mediated by the neonatal Fc receptor. Nature Biotechnology. 2011; 29:158-163. Editorial Commentary: FcRn-Escorted Mucosal Vaccine. News and Views: McGhee JR. A Mucosal Gateway For Vaccines. Nature Biotechnol. 2011; 29:136-138. Evaluated by Faculty of 1000 Biology as a “Must Read” paper.
- Patel D, Nan Y, Shen M, Ritthipichai K, Zhu X, Zhang YJ. Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation. Journal of Virology. 2010; 84:11045-55.
- Ye L, Tuo W, Liu X, Simister NE, Zhu X. Identification and characterization of an alternatively spliced variant of the MHC class I-related porcine neonatal Fc receptor for IgG. Developmental & Comparative Immunology. 2008; 32:966-979.
- Liu X, Ye L, Bai Y, Mojidi H, Simister NE, Zhu X. Activation of the JAK/STAT-1 signaling pathway by IFN-gamma can down-regulate functional expression of the MHC class I-related neonatal Fc receptor for IgG. Journal of Immunology. 2008; 181:449-63. (Featured article in this issue: IFN-gamma Stops the Mucosal IgG Pipeline).
- Ye L, Liu X, Rout SN, Li Z, Yan Y, Lu L, Kamala T, Nanda NK, Song W, Samal SK, Zhu X. The MHC class II-associated invariant chain interacts with the neonatal Fc gamma receptor and modulates its trafficking to endosomal/lysosomal compartments. Journal of Immunology. 2008; 181:2572-85. (Featured article in this issue: A New Partner for Invariant Chain)
- Xu J, Laine O, Masciocchi1 M, Manoranjan J, Smith J, Du SJ, Edwards N, Zhu X, Fenselau C, and Gao LY. A unique Mycobacterium ESX-1 protein co-secretes with CFP-10/ESAT-6 and is necessary for inhibiting phagosome maturation. Molecular Microbiology. 2007, 111:1365-2958.
- Liu X, Ye L, Christianson GJ, Yang JQ, Roopenian DC, Zhu X. NF-kappaB signaling regulates functional expression of the MHC class I-related neonatal Fc receptor for IgG via intronic binding sequences. Journal of Immunology. 2007; 179:2999-3011.(Featured article in this issue: The Importance of Introns in FcRn)
- Zhu X*, Peng J, Chen D, Liu X, Ye L, Iijima H, Kadavil K, Lencer WI, Blumberg RS*. Calnexin and ERp57 facilitate the assembly of the neonatal Fc receptor for IgG with beta 2-microglobulin in the endoplasmic reticulum. Journal of Immunology. 2005; 175:967-976. (*Corresponding Author)
