Contact

Location: 5.016V.5 - MED

Department

Microbiology, Immunology & Molecular Genetics

Zhang, Nu, Ph.D.

Associate Professor

Personal Statement:

Dr. Zhang studies the mechanisms underlying the differentiation and retention of tissue resident memory T cells controlled by transforming growth factor-beta (TGF-B) signaling following acute infections. Dr. Zhang has the expertise and motivation necessary to successfully carry out the prosed work. He has a solid background in immunology, with specific training and expertise in key research areas.

Dr. Zhang’s lab website: http://nuzhanglab.org/

Education

Ph.D., Immunology at Duke University

Research

Keywords: Tissue-Resident Memory T Cells Research interests: The long-term goal of my research is to understand the biology and function of tissue-resident memory T (Trm) cells and tumor infiltrating T cells in health and disease, and the role of Transforming Growth Factor-β (TGF-β) in their differentiation, homeostasis and metabolic regulation.

  • Metabolic reprogram has been associated with memory T cell differentiation. However, the signals that control T cell metabolism remain elusive.
  • Infectious diseases are a big burden to society. Many pathogens invade the body through local tissues. The early stage of infection, while the pathogen is confined to these localized sites, provides the ideal window of opportunity for an effective immune response. Trm cells, a newly identified population of memory T cells, resident in a variety of peripheral tissues, are ideally situated to act during this window and stall the infection. TGF-β is essential for the differentiation of Trm cells in the skin, lung and gut. However, the molecular and cellular mechanisms controlling Trm cells are largely unknown.
  • Cancer remains as one of the leading causes of death worldwide. Tumor infiltrating T cells are associated with the overall survival of cancer patients. Providing the phenotypic similarities between Trm and tumor infiltrating T cells, it remains to be determined whether tumor infiltrating T cells are regulated by similar mechanisms as Trm cells.

Keeping these important questions in mind, we are going to focus on TGF-β-dependent metabolic programs, Trm cells and tumor infiltrating T cells under various in vivo settings.

Awards & Accomplishments

Awards

10/2022         VA Merit Award

4/2021            W. M. Keck Foundation Grant for Medical Research. Dr. Zhang served as Co-PI on this award.

10/2019         Rising Research Superstars Award from Long School of Medicine

1/2018            American Cancer Society Research Scholar grant Award

12/2017         Faculty of the Year: Annual Award from Department of MIMG

07/2015         Voelcker Young Investigator Award

11/2014         University of Texas System Rising STARs Award

Active Grants
Project #: BX005955-01
Funding Agency: VA Merit Award
Title: Targeting lymphoid tissue residency to boost tumor immunotherapies
Role: PI
Project #: R01 AI125701
Funding Agency: NIH/NIAID
Title: Mechanistic study of TGF-β-dependent control of gut-resident memory T cells
Role: PI
Project #: R21 AI166843
Funding Agency: NIH/NIAID
Title: The impact of aging and thymus regeneration on tissue-resident CD8 T cell responses to viral lung infection and vaccination
Role: Co-PI
Funding Agency: Keck Foundation (Subaward via George Washington University)
Title: RNA Polymerase II Pausing in Cellular Memory
Role: Co-PI
Project #: RGS-18-222-01-LIB
Funding Agency: American Cancer Society
Title: Stroma and T cell interaction controls Tcf1 CD8 T cells in tumor immunity
Role: PI

Affiliations

  • The Cancer Therapy and Research Center (CTRC)

Lab Members

Zhang Lab Website

Dr. Chaoyu Ma (Research Scientist)

Kenneth Ka-Ho Fan (Graduate Student)

Saranya Srinivasan (Graduate Student)

Courtney Segura (Research Technician)

Publications

Complete List of Publications

 

  1. Chaoyu Ma, Liwen Wang, Wei Liao, Yong Liu, Shruti Mishra, Guo Li, Xin Zhang, Yuanzheng Qiu, Qianjin Lu and Nu Zhang. TGF-b promotes stem-like T cells via enforcing their lymphoid retention. J. Exp. Med. In Press.
  2. Yinghong Hu, William Hudson, Christopher Medina, Antonio Baptista, Chaoyu Ma, Wei Liao, Ronald Germain, Nu Zhang and Rafi Ahmed. TGF-b regulates the transcriptional program and quiescence of virus-specific PD-1+Tcf-1+ CD8 T cells during chronic LCMV infection. J. Exp. Med. In Press.
  1. Chao Li, Yang-Ding Lin, Wei-Bei Wang, Ming Xu, Nu Zhang and Na Xiong. Differential regulation of adaptive CD8+CD86+Vg1+gd T cell responses in skin barrier tissue protection and homeostatic maintenance. Euro. J. Immunol. 2022 May, 27. Doi: 10.1002/eji.202249793.
  2. Bogang Wu, Xiaowen Zhang, Huai-Chin Chiang, Haihui Pan, Bin Yuan, Payal Mitra, Leilei Qi, Hayk Simonyan, Colin N. Young, Eric Yvon, Yanfen Hu, Nu Zhang, Rong Li. RNA polymerase II pausing factor NELF in CD8+ T cells promotes antitumor immunity. Commun. 2022, 13, 2155. DOI: 10.1038/s41467-022-29869-2.
  1. Grace C Lee, Marcos I Restrepo, Nathan Harper, Muthu Saravanan Manoharan, Alisha M Smith, Justin A Meunier, Sandra Sanchez-Reilly, Aamir Ehsan, Anne P Branum, Caitlyn Winter, Lauryn Winter, Fabio Jimenez, Lavanya Pandranki, Andrew Carrillo, Graciela L Perez, Antonio Anzueto, Hanh Trinh, Monica Lee, Joan M Hecht, Celida Martinez, Raj T Sehgal, Jose Cadena, Elizabeth A Walter, Kimberly Oakman, Raymond Benavides, Jacqueline A Pugh, South Texas Veterans Health Care System, Scott Letendre, Maristella Steri, Valeria Orrù, Edoardo Fiorillo, Francesco Cucca, Alvaro G Moreira, Nu Zhang, Elizabeth Leadbetter, Brian K Agan, Douglas D Richman, Weijing He, Robert A Clark, Jason F. Okulicz and Sunil K Ahuja. Immunologic resilience and COVID-19 survival advantage. J. Allergy Clin. Immunol. 2021 Sept 8; Doi: 10.1016/j.jaci.2021.08.021.
  2. Alisha M. Smith, Nathan Harper, Justin A. Meunier, Anne P. Branum, Fabio Jimenez, Lavanya Pandranki, Andrew Carrillo, Charles S. Dela Cruz, Marcos I. Restrepo, Diego J. Maselli, Cynthia G. Rather, Anna H. Heisser, Daniel A. Ramirez, Weijing He, Robert A. Clark, Charles P. Andrews, Scott E. Evans, Jacqueline A. Pugh, Nu Zhang, Grace C. Lee, Alvaro G. Moreira, Leopoldo N. Segal, Robert M. Ramirez, Robert L. Jacobs, Muthu Saravanan Manoharan, Jason F. Okulicz, Sunil K. Ahuja. Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases. J. Allergy Clin. Immunol. 2021 Jan 23; Doi: 10.1016/j.jaci.2021.01.008.
  1. Shruti Mishra, Saranya Srinivasan, Chaoyu Ma and Nu Zhang. CD8+ regulatory T cell – A mystery to be revealed. Immunol. 18 Aug. 2021. DOI: 10.3389/fimmu.2021. 708874.
  1. Wei Liao, Yong Liu, Chaoyu Ma, Guo Li, Shruti Mishra, Liwen Wang, Saranya Srinivasan, Kenneth Ka-Ho Fan, Haijing Wu, Qianwen Li, Ming Zhao, Xun Liu, Erika L. Demel, Xin Zhang, Yuanzheng Qiu, Qianjin Lu and Nu Zhang. The downregulation of IL-18R defines bona fide kidney-resident CD8+ T cells. iScience. 2021 Jan 22; 24 (1), 101975. Doi: 10.1016/j.isci.2020.101975.
  1. Li She, Gema D Barrera, Liping Yan, Hamad Hazzaa Alanazi, Edward G Brooks, Peter H Dube, Yilun Sun, Hong Zan, Daniel P Chupp, Nu Zhang, Xin Zhang, Yong Liu, Xiao-Dong Li. STING activation in alveolar macrophages and group 2 innate lymphoid cells suppresses IL-33-driven type 2 immunopathology. JCI insight. Doi:10.1172/jci.insight.143509.
  2. Nick P. Goplen, Yue Wu, Young Min Song, Chaofan Li, Zheng Wang, In Su Cheon, Li Jiang, Bibo Zhu, Katayoun Ayasoufi, Eduardo N. Chini, Aaron J. Johnson, Robert Vassallo, Andrew H. Limper, Nu Zhang and Jie Sun. Tissue-resident CD8+ T cells drive age-associated chronic lung sequelae following viral pneumonia. Immunol. 2020 Nov 6; 5 (53), eabc4557. Doi:10.1126/sciimmunol.abc4557.
  3. Shruti Mishra, Wei Liao, Yong Liu, Ming Yang, Chaoyu Ma, Haijing Wu, Ming Zhao, Xin Zhang, Yuanzheng Qiu, Qianjin Lu and Nu Zhang. TGF-b and Eomes control the homeostasis of CD8+ regulatory T cells. Exp. Med. 2020. Sep 29; 218 (1). e20200030
  4. Wei Liao, Chaoyu Ma, Nu Zhang. Isolation of Mouse Kidney-Resident CD8+ T cells for Flow Cytometry Analysis. Vis. Exp. 2020. Jun 27; (160). Doi:10.3791/61559.
  5. Henrique Borges da Silva, Changwei Peng, Haiguang Wang, Kelsey M. Wanhainen, Chaoyu Ma, Sharon Lopez, Alexander Khoruts, Nu Zhang, Stephen C. Jameson. Extracellular ATP sensing via P2RX7 promotes CD8+ tissue-resident memory T cells by enhancing TGF-β sensitivity. Immunity. 2020 Jul 14; 53(1): 158-171.e6. doi:10.1016/ j.immuni.2020.06.010.
  6. Tian Q, Zhou Z, Wang L, Abu-Khdeir AH, Huo Z, Sun X, Zhang N, Schenken R, Wang Y, Xue M, Zhong G. Gastrointestinal co-infection promotes chlamydial pathogenicity in the genital tract. Immun. 2020 Jan 27. pii: IAI.00905-19. Doi: 10.1128/IAI.00905-19.
  7. John Koprivsek, Ying He, Chenchen Song, Nu Zhang, Alexei Tumanov, and Guangming Zhong. Evasion of innate lymphoid cells regulated IFN-g responses by Chlamydia muridarum to achieve long-lasting colonization in mouse colon. Immun. 2019 Dec 9. pii: IAI.00798-19. doi: 10.1128/IAI.00798-19.
  8. Wang Z, Wang S, Goplen NP, Li C, Cheon IS, Dai Q, Shan J, Ma C, Ye Z, Xiang M, Limper AH, Porquera E-C, Kohlmeier JE, Kaplan MH, Zhang N, Johnson AJ, Vassallo R, Sun J. Exhausted-like CD8 resident memory T cells balance immunity and fibrotic sequelae. Science Immunology2019 Jun 14; 4 (36). Pii:eaaw1217.
  9. Yong Liu, Chaoyu Ma and Nu Zhang. Tissue-specific control of tissue resident memory T cells. Rev. Immunol. 2018 DOI:10.1615/CritRevImmunol. 2018025653