Jian Zheng, MD, PhD

 

 

Research Interests

1. Host immune responses to coronaviruses and other respiratory virus infections. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major global threat, and the likelihood of another CoV outbreak looms large over humanity. However, the progression of virus-related disease is never a solo dance of pathogens but is modulated by host immune responses. Human lungs are the organ with the largest surface area in our bodies, in constant contact with external environment. A comprehensive understanding of the roles of airway-resident immunity and its interaction with systemic immune responses during viral infections will be key to unlocking the pathogenesis of CoVs and other respiratory virus infections, especially seasonal influenza virus infection.

2. Aged-related immunoregulation and inflammation in the respiratory system. Unlike solid organs, the development and maturation of the lung continues after birth and lasts into adulthood. During aging of hosts, progressively decreased lung function, accompanied by structural changes in the respiratory tract and biological changes in resident and circulating cells, leads to impaired gas exchange and predisposition to infectious diseases and tumors. Therefore, elucidating aged-related immune modulation in the respiratory system is vital to enable us to confront increasing health problems in an aging society. We will specifically focus on aging-dependent signaling pathways, such as the PLA2G2D-PGD2-DP1 pathway, and their roles in inflammatory diseases.

3. Translational Medicine.My medical background motivates my enthusiasm for bridging basic science research outcomes to their clinical application. Establishing animal models that reflect key characteristics of human diseases represents a critical step in translational medicine and will be a major focus of my lab. Host factor-targeting treatments could be potential solutions to counteract viral evolution. In my previous investigations, my colleagues and I explored new applications of “old” drugs for treating respiratory virus infections and other diseases. By collaborating with clinicians, chemists, and biopharmaceutical companies, I am dedicated to exploring novel therapies and preventive strategies against respiratory virus infections and other immune disorder-related diseases.

 

Selected Publications

  1. Wong LYR, Zheng J, Wilhelmsen K, Li K, Ortiz ME, Schnicker NJ, Pezzulo AA, Szachowicz PJ, Klumpp K, Aswad F, Rebo J, Narumiya S, Murakami M, Meyerholz DK, Fortney K, McCray PB Jr, Perlman S. 2021. Eicosanoid signaling as a therapeutic target in middle-aged mice with severe COVID-19. Nature. (Co-first author)
  2. Dampalla C, Zheng J, Perera K, Wong LYR, Meyerholz DK, Nguyen H, Kashipathy M, Battaile K, Lovell S, Kim Y, Perlman S, Groutas W, Chang KO. 2021. Post-infection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection. PNAS. 118 (29). (co-first author)
  3. Zheng J, Meyerholz DK, Wong LYR, Gelb M, Murakami M, Perlman S. 2021. Coronavirus-specific antibody production in middle-aged mice requires phospholipase A2G2D. J Clin Invest. 131 (11).
  4. Zheng J, Wen L, Yen HL, Liu M, Liu Y, Teng O, Wu WF, Ni K, Lam KT, Huang C, Yang J, Lau YL, Perlman S, Peiris M, Tu W. 2021. Phenotypic and functional characteristics of a novel influenza hemagglutinin-specific memory NK cell. J Virol. 95 (12), e00165-21.
  5. Zheng J, Wang Y, Li K, Meyerholz DK, Allamargot C, Perlman S. 2020. SARS-CoV-2-induced immune activation and death of monocyte-derived human macrophages and dendritic cells. J Infect Dis. 223 (5), 785-795.
  6. Zheng J, Wong LYR, Li K, Verma AK, Ortiz ME, Wohlford-Lenane C, Leidinger MR, Knudson CM, Meyerholz DK, McCray PB Jr., Perlman S. 2020. COVID-19 Treatments and Pathogenesis including Anosmia in K18-hACE2 Mice. Nature. 589 (7843), 603-7.
  7. Zheng J, Sariol A, Meyerholz DK, Zhang Q, Abrahante Lloréns JE, Narumiya S, Perlman S. 2020. Prostaglandin D2 signaling in dendritic cells is critical for the development of EAE. J Autoimmun. 114, 102508.
  8. Rathnayake AD, Zheng J, Kim Y, Perera KD, Mackin S, Meyerholz DK, Kashipathy MM, Battaile KP, Lovell S, Perlman S, Groutas WC, Chang KO. 2020. 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice. Sci Transl Med. 12 (557), eabc5332. (Co-first author)
  9. Sun J, Zhuang Z, Zheng J, Li K, Wong LYR, Liu D, Huang J, He J,  Zhu A, Zhao J, Li X, Xi Y, Chen R, Alshukairi AN, Chen Z,  ZhangZ, Chen C,  Huang X,  Li F, Lai X, Chen D, Wen L, Zhuo J,  Zhang Y, Wang Y, Huang S, Dai J, Shi Y,  Zheng K, Leidinger MR, Chen J, Li Y, Zhong N, Meyerholz DK, McCray PB Jr., Perlman S, Zhao J. 2020. Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment. Cell. Aug 6; 182(3): 734–743.e5. (Co-first author)
  10. Zheng J, Hassan S, Alagaili AN, Alshukairi AN, Amor NMS, Mukhtar N, Nazeer IM, Tahir Z, Akhter N, Perlman S, Yaqub T. 2019. Middle East Respiratory Syndrome Coronavirus Seropositivity in Camel Handlers and Their Families, Pakistan. Emerg Infect Dis. Dec;25(12).
  11. Alshukairi AN, Zheng J, Zhao J, Nehdi A, Baharoon SA, Layqah L, Bokhari A, Al Johani SM, Samman N, Boudjelal M, Ten Eyck P, Al-Mozaini MA, Zhao J, Perlman S, Alagaili AN. 2018. High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia. MBio. Oct 30;9(5). pii: e01985-18. (Co-first author)
  12. Liu M, Zhou C, Zheng J*. 2015. Cigarette smoking impairs the response of EGFR-TKIs therapy in lung adenocarcinoma patients by promoting EGFR signaling and epithelial-mesenchymal transition. Am J Transl Res. 15;7(10):2026-35.
  13. Xiang Z, Liu Y, Zheng J, Liu M, Lv A, Gao Y, Hu H, Lam KT, Chan GC, Yang Y, Chen H, Tsao GS, Bonneville M, Lau YL, Tu W. 2014. Targeted activation of human Vγ9Vδ2-T cells controls Epstein-Barr virus-induced B cell lymphoproliferative disease. Cancer Cell. 26:565-76.
  14. Zheng J, Liu Y, Liu Y, Liu M, Xiang Z, Lam KT, Lewis DB, Lau YL, Tu W. 2013. Human CD8+ Regulatory T cells Inhibit GVHD and Preserve General Immunity in Humanized Mice. Sci Transl Med. 5:168ra9.
  15. Zheng J, Liu Y, Qin G, Lam KT, Guan J, Xiang Z, Lewis DB, Lau YL, Tu W. 2011. Generation of human Th1-like regulatory CD4+ T cells by an intrinsic IFN-gamma- and T-bet-dependent pathway. Eur J Immunol. 41: 128-39.
  16. Tu W, Zheng J, Liu Y, Sia SF, Liu M, Qin G, Ng IH, Xiang Z, Lam KT, Peiris JS, Lau YL. 2011. The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a gammadelta T cell population in humanized mice. J Exp Med. 208: 1511-22.
  17. Zheng J, Liu Y, Lau YL, Tu W. 2010. CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells. Cell Mol Immunol. 7: 44-50.
  18. Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, Chan PL, Lam KT, Guan J, Zhang L, Guan Y, Yuen KY, Peiris JS, Lau YL. 2010. Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol. 84: 6527-35. (Co-second author)
  19. Zheng J, Liu Y, Qin G, Chan PL, Mao H, Lam KT, Lewis DB, Lau YL, Tu W. 2009. Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells. J Immunol. 183: 3742-5.
  20. Tu W, Lau YL, Zheng J, Liu Y, Chan PL, Mao H, Dionis K, Schneider P, Lewis DB. 2008. Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells. Blood. 112: 2554-62.