Zheng Lab

About 

Host immune responses to coronaviruses and other respiratory virus infections. Although the application of vaccines and anti-viral drugs significantly reduced the mortality and morbidity of COVID-19 patients, SARS-CoV-2 variants continue to represent a global threat. In addition, the likelihood of another CoV outbreak looms large over humanity. Airway is covered with the largest mucosa in human body, in constant contact with external environment. A comprehensive understanding of the roles of airway-resident immunity modulated by respiratory virus infection, as well as its interaction with systemic immune responses during/post infection is the key to unlocking the pathogenesis of acute virus infections and post-acute sequelae. By using animal models, we aim to clarify virus-induced immune dysregulations and explore potential targeting prevention and therapy.

Aged-related immunoregulation and inflammation in respiratory system. Unlike most organs, the development and maturation of the lung continues after birth and lasts into adulthood. During aging, progressively decreased lung function, accompanied by structural remodeling of the airway and biological modifications of resident and circulating cells, leads to pathological changes. Therefore, elucidating aged-related immune disorders in respiratory system is vital to confront increasing health problems in an aging world. Our lab focus on aging-dependent signalings, such as the PLA₂G2D-PGD₂/DP1 pathway, and their roles in inflammatory diseases.

Translational Medicine. Establishing animal models that reflect key characteristics of human diseases represents a critical step in translational medicine and a major focus of my lab. Host factor-targeting treatments could be potential solutions to counteract viral evolution. In our previous investigations, we explored new applications of “old” drugs for treating respiratory virus infections and other diseases. By collaborating with clinicians, chemists, and biopharmaceutical companies, we are dedicated to exploring novel therapies and preventive strategies against respiratory virus infections and other immune disorder-related diseases.

Key Research Areas

• Pathogenesis of coronavirus and other respiratory virus infection
• Pathogenesis of post-acute sequelae of virus infection
• Immunotherapy against virus infection and related inflammation
• Pathogenesis of aging-related inflammatory diseases
• Development of novel translational disease models

Current Projects

• Immune disorders caused by SARS-CoV-2 infection
• Pathogenesis of coronavirus-related CNS inflammation
• Aging-related increase of PLA₂G2D-PGD₂/DP1 signaling pathway contribute to inflammaging
• PLA₂G2D-PGD₂/DP1-targeting therapy in treating solid tumors
• The roles of microbiota and metabolism in aging lung immunity

Team 

• Jian Zheng, MD, PhD (Principal Investigator)
• Divyasha Saxena (Research Scientist)
• Kelly Walter, MS (M&I PhD Candidate, 2022)
• Dante Hamiel, MS (M&I PhD Candidate, 2023)
• Orlando Nano Grimany BS (Senior Technician, Lab Manager)

Recent Publications

• Ye G, Bu F, Pan R, Mendoza A, Saxena D, Zheng J, Perlman S, Liu B, Li F. 2024. Dual-role epitope on SARS-CoV-2 spike enhances and neutralizes viral entry across different variants. PLoS pathogens 20 (9), e1012493

• Shi J, Zheng J, Zhang X, Tai W, Compas R, Deno JC, Jachym N, Verma AK, Wang G, Guan X, Odle AE, Wan Y, Li F, Perlman S, Qiao L, Du L. 2024. A T cell-based SARS-CoV-2 spike protein vaccine provides protection without antibodies. JCI Insight 9(5):e155789.

• Ghimire S, Xue B, Li K, Gannon RM, Wohlford-Lenane CL, Thurman AL, Gong H, Necker GC, Zheng J, Meyerholz DK, Perlman S, McCray PB Jr, Pezzulo AA. 2024. IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo. BioRxiv.

• Laro JA, Xue B, Zheng J, Ness M, Perlman S, McCall LI. 2024. SARS-CoV-2 infection unevenly impacts metabolism in the coronal periphery of the lungs. BioRxiv.

• Zheng J, Channappanavar R, Perlman S. 2023. Immunization of MERS-CoV-2-infected mice with a sublethal dose of MERS-CoV or VRP-MERS-S. STAR protocols 4 (2), 102171.

• Zhang Y, Sun J, Zheng J, Li S, Rao H, Dai J, Zhang Z, Wang Y, Liu D, Chen Z, Ran W, Zhu A, Li F, Yan Q, Wang Y, Yu K, Zhang S, Wang D, Tang Y, Liu B, Cheng L, Huo J, Perlman S, Zhao J, Zhao J. 2023. Mosaic RBD nanoparticles elicit protective immunity against multiple human coronaviruses in animal models. Adv Sci (Weinh). 11(9): e2303366.

• Ye G, Pan R, Bu F, Zheng J, Mendoza A, Wen W, Du L, Spiller B, Wadzinski BE, Liu B, Perlman S, Li F. 2023. Discovery of Nanosota-2,-3, and-4 as super potent and broad-spectrum therapeutic nanobody candidates against COVID-19. J Virol 97(11): e01448-23.

• Tai W, Zheng J, Zhang X, Shi J, Wang G, Guan X, Zhu J, Perlman S, Du L. 2023. MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection. Virus Res 334, 199156.

• Shi J, Wang G, Zheng J, Verma AK, Guan X, Malisheni MM, Geng Q, Li F, Perlman S, Du L. 2022. Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern. NPJ Vaccines. 7: 169.

• Verma A, Zheng J, Meyerholz DK, Perlman S. 2022. SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways. JCI Insight. 7(24): e160277.

• El-Kafrawy SA, Odle AE, Abbas AT, Hassan AM, Abdel-Dayem UA, Qureshi AK, Wong LYR, Zheng J, Meyerholz DK, Perlman S, Zumla A, Azhar EI. 2022. SARS-CoV-2-specific immunoglobulin Y antibodies are protective in infected mice. PLoS Pathogens. 18(9): e1010782.

• Shi J, Zheng J, Tai W, Verma AK, Zhang X, Geng Q, Wang G, Guan X, Malisheni MM, Odle AE, Zhang W, Li F, Perlman S, Du L. 2022. A Glycosylated RBD Protein Induces Enhanced Neutralizing Antibodies against Omicron and Other Variants with Improved Protection against SARS-CoV-2 Infection. J Virol. 96 (17), e00118-22. (co-first author)

• Shi J, Zheng J, Zhang X, Tai W, Odle AE, Perlman S, Du L. 2022. RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge. Transl Res 248:11-21. (co-first author)

• Verma A, Zheng J, Ginhoux F, Mack M, Perlman S. 2021. Differential effects of prostaglandin D2 signaling in macrophages and microglia in murine coronavirus encephalomyelitis. mBio. 12 (5), e01969-21.

• Wong LYR, Zheng J, Sariol A, Lowery S, Meyerholz DK, Gallagher T, Perlman S. 2021. Middle East respiratory syndrome coronavirus Spike protein variants exhibit geographic differences in virulence. PNAS. 118:e2102983118.

• 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 signalling blockade protects middle-aged mice from severe COVID-19. Nature. 605 (7908): 146-151. (Co-first author)

• Zheng J, Meyerholz DK, Wong LYR, Gelb M, Murakami M, Perlman S. 2021. Coronavirus-specific antibody production in middle-aged mice requires phospholipaseA2G2D. J Clin Invest. 131(11).

• 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): e2101555118. (co-first author)

• Dampalla CS, Kim Y, Bickmeier N, Rathnayake AD, Nguyen HN, Zheng J, Kashipathy MM, Baird MA, Battaile KP, Lovell S, Perlman S, Chang KO, Groutas WC. 2021. Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease. J Med Chem. 64 (24), 17846-17865.

• Dampalla CS, Kim Y, Bickmeier N, Rathnayake AD, Nguyen HN, Zheng J, Kashipathy MM, Baird MA, Battaile KP, Lovell S, Perlman S, Chang KO, Groutas WC. 2021. Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease. J Med Chem. 64(24): 17846-17865.

• Yu AD, Galatsis K, Zheng J, Le JQ, Ma D, Perlman S, Rosbash M. 2021. Development of a saliva-optimized RT-LAMP assay for SARS-CoV-2.  J Bio Tech. 32 (3), 102.

• Ye G, Gallant JP, Massey C, Shi K, Tai W, Zheng J, Odle AE, Vickers MA, Shang J, Wan Y, Drelich A, Kempaiah KR, Tat V, Perlman S, Du L, Tseng CT, Aihara H, LeBeau AM, Li F. 2021. The Development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates. eLife. 10, e64815.

• 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.

A full list of Zheng Lab publications may be found here.