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Dr. Cheng, Yang

Assistant Research Fellow
  • 2789-9097 (Lab) (Room No: N401)
  • 2652-3966 (Office)

Specialty:
  • Human T cell biology, virus-specific memory T cells
  • Highly multiplexed combinatorial pMHC tetramer staining
  • Single-cell multi-omics
  • T cell receptor
  • High-dimensional analysis

Education and Positions:
  • M.Sc., University College London
    Ph.D., Nanyang Technological University – A*STAR joint program
    Postdoc Fellow, Singapore Immunology Network, A*STAR
    Senior Research Scientist, Massachusetts General Hospital, Harvard Medical School


Decoding Human Virus-Specific Adaptive Immunity

 

Deep-profiling tissue-resident memory T cells during viral infection and virus-associated cancer

Current knowledge of human T cell biology is often limited to the study of total T cell population without the understanding of antigen-specific immunity due to the lack of apparent T cell epitopes. In addition, most of the studies only investigate peripheral T cells without encompassing site-specific responses in human tissues, where the diseases usually occur. These prevent the accurate interpretation of disease-specific immune responses and restrain the therapeutic implications of findings. Our goal is to dissect the complexity of virus-specific CD8+ T cell responses detected in healthy versus diseased blood and tissue samples. We are particularly interested in chronic viral (e.g., hepatitis B virus, HBV) infection, HBV-associated liver diseases, and SARS-CoV-2 infection. Combining the usages of highly multiplexed combinatorial peptide-MHC tetramer staining, mass cytometry, and other single-cell multi-omics, we aim to comprehensively investigate the T cell antigen-specificities, virus-reactive T cell receptors (TCR), and cellular phenotypes across human tissues, with a focus on the characteristics of tissue-resident memory T (TRM) cells and exhausted T (TEX) cells. We believe our work can facilitate the fundamental understanding of human T cell biology, improve immunotherapeutics against cancer, and advance the next generation of vaccine design.
https://jrnlclub.org/research-films/trm-hbv-hcc

Probing virus-specific CD4+ T cells and the long-term immune protection induced by viral infection or vaccination

As the central component of human adaptive immunity, CD4+ “helper” T cells are essential for the generation and maintenance of robust cellular (CD8+ T cell) and humoral (B cell and antibody) immune responses. Our goal is to use peptide-MHCII tetramer and antigen-probe to identify the relevant virus-specific CD4+ T cell subset (e.g., follicular helper T cells, TFH) and the interacting virus-specific B cells that confer long-term immune protection during the event of viral antigen seroconversion or vaccination.

Early life immunity upon emerging viral infection or vaccination

Newborn immune system is greatly shaped by early exposure of pathogens or immunization through early life. We want to uncover the underlying immunological basis that regulate virus-specific immune response in utero and long-term immune protection of newborn. Our objective is to decipher the maternal-fetal immune interaction, describe the important adaptive immune networks, and establish the key features of immune responses upon viral infection or vaccination (e.g., SARS-CoV-2 and HBV) in early phase of human life.

Using cutting-edge methods to explore and visualize the high-dimensional complexity of immune cells

The lab is experienced in combining the utility of mass cytometry (CyTOF), high-parameter spectral flow cytometry, single-cell analytical tools, and high-dimensional analysis, to delve into the biological insights of human immune responses.

Journal 19 Book 0

  1. Mattox AK, Roelands J, Saal TM, (Cheng Y), Rinchai D, Hendrickx W, Young GD, Diefenbach TJ, Berger AE, Westra WH, Bishop JA, Faquin WC, Marincola FM, Pittet MJ, Bedognetti D, Pai SI* Myeloid Cells Are Enriched in Tonsillar Crypts, Providing Insight into the Viral Tropism of Human Papillomavirus. AMERICAN JOURNAL OF PATHOLOGY 191(10), 1774-1786 (2021-10) [JCR] [WOS]
  2. (Cheng Y), Gunasegaran B, Singh HD, Dutertre CA, Loh CY, Lim JQ, Crawford JC, Lee HK, Zhang X, Lee B, Becht E, Lim WJ, Yeong J, Chan CY, Chung A, Goh BKP, Chow PKH, Chan JKY, Ginhoux F, Tai D, Chen J, Lim SG, Zhai W, Choo SP, Newell EW* Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma. IMMUNITY 54(8), 1825-1840.e7 (2021-08-10) [JCR] [WOS]
  3. Le Bert N, Gill US, Hong M, Kunasegaran K, Tan DZM, Ahmad R, (Cheng Y), Dutertre CA, Heinecke A, Rivino L, Tan A, Hansi NK, Zhang M, Xi S, Chong Y, Pflanz S, Newell EW, Kennedy PTF, Bertoletti A* Effects of Hepatitis B Surface Antigen on Virus-Specific and Global T Cells in Patients With Chronic Hepatitis B Virus infection. GASTROENTEROLOGY 159(2), 652-664 (2020-08) [JCR] [WOS]
  4. Dress RJ, Dutertre CA, Giladi A, Schlitzer A, Low I, Shadan NB, Tay A, Lum J, Kairi MFBM, Hwang YY, Becht E, (Cheng Y), Chevrier M, Larbi A, Newell EW, Amit I, Chen J, Ginhoux F* Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage. NATURE IMMUNOLOGY 20(7), 852-864 (2019-07) [JCR] [WOS]
  5. (Cheng Y), Zhu YO, Becht E, Aw P, Chen J, Poidinger M, de Sessions PF, Hibberd ML, Bertoletti A, Lim SG, Newell EW* Multifactorial heterogeneity of virus-specific T cells and association with the progression of human chronic hepatitis B infection. SCIENCE IMMUNOLOGY 4(32), NA-NA (2019-02-08) [JCR] [WOS]
  6. Becht E, Simoni Y, Coustan-Smith E, Evrard M, (Cheng Y), Ng LG, Campana D, Newell EW* Reverse-engineering flow-cytometry gating strategies for phenotypic labelling and high-performance cell sorting. BIOINFORMATICS 35(2), 301-308 (2019-01-15) [JCR] [WOS]
  7. Rivino L, Le Bert N, Gill US, Kunasegaran K, (Cheng Y), Tan DZ, Becht E, Hansi NK, Foster GR, Su TH, Tseng TC, Lim SG, Kao JH, Newell EW, Kennedy PT, Bertoletti A* Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. JOURNAL OF CLINICAL INVESTIGATION 128(2), 668-681 (2018-02-01) [JCR] [WOS]
  8. Sumatoh HR, Teng KW, (Cheng Y), Newell EW* Optimization of mass cytometry sample cryopreservation after staining. CYTOMETRY PART A 91(1), 48-61 (2017-01) [JCR] [WOS]
  9. Newell EW* and (Cheng Y) Mass cytometry: blessed with the curse of dimensionality. NATURE IMMUNOLOGY 17(8), 890-895 (2016-07-19) [JCR] [WOS]
  10. (Cheng Y), Wong MT, van der Maaten L, Newell EW* Categorical Analysis of Human T Cell Heterogeneity with One-Dimensional Soli-Expression by Nonlinear Stochastic Embedding. JOURNAL OF IMMUNOLOGY 196(2), 924-932 (2016-01-15) [JCR] [WOS]

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Wang, Yiwen
Wang, Yiwen
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Cho, Tsai-Ting
Cho, Tsai-Ting