Institute of Biomedical Science, Academia Sinica

LABORATORY OF HUMAN VIRUS IMMUNOLOGY

Yang Cheng
https://thechenglab.com/

Research Field

Medicine

Introduction

Dr. Cheng completed his doctoral and the first post-doctoral training at Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR) with Dr. Evan Newell, the pioneer in the use of highly multiplexed combinatorial peptide-MHC tetramer technology and mass cytometry to examine human antigen-specific T cells in health and disease. He has focused his research in human chronic HBV infection and liver cancer, and developed unique expertise in studying low frequency antigen-specific T cell responses in human clinical samples, through a combination of highly multiplexed pMHC tetramer, mass cytometry, high-dimensional single-cell techniques and analytical methods. Dr. Cheng published his seminal works in journal such as Science Immunology and Immunity, where he simultaneously probed >500-1000 T cell epitopes in chronic HBV infected patients or HBV-associated hepatocellular carcinoma (HCC) patients. He uncovered novel HBV-specific memory T cell responses and public HBV-reactive TCR clones associated with viral control in Asian population. Expanding his expertise toward HBV-associated HCC,  Dr. Cheng demonstrating the casual link between non-terminally exhausted HBV-specific tissue-resident memory CD8+ T cells in tumors and patient’s relapse-free survival. His work showed that HBV-specific T cells have effective anti-tumor response, implying that these cells could be harnessed for therapeutic purposes. This study is well-received by the scientific community, and featured by two commentary articles in Immunity and Cancer Discovery. Dr. Cheng also made substantial contributions in the fields of mass cytometry and high-dimensional data analysis (Newell & Cheng. Nature Immunology. 2016; Cheng & Newell. Adv in Immunology. 2016; Cheng et al. Journal of Immunology. 2016). Dr. Cheng is also actively involved in the international community of immunologists. He is currently serving as a member of organizing committee of Early Career Immunology (https://www.earlycareerimmunology.com/), a digital seminar series  that promotes emerging immunologists in their early career around the world.

Dr. Cheng aim to extend his expertise and the cutting-edge technology platforms to dissect human virus-specific T cells across different viral infections and immune-related diseases, and explore the relationship between the tissue residency of T cells and long-term immune protection. Our long-term goal is to translate T cell-based therapeutics for improving the clinical benefit of patients.

Human memory T cells are critical in controlling the immune protection upon vaccination, or during the progression of viral infection and virus-associated cancer. Current knowledge of human T cell biology has been 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. The Cheng Laboratory focuses on combining the usage of highly multiplexed combinatorial peptide-MHC tetramer staining, mass cytometry, single-cell multi-omics, T cell receptor sequencing, high-dimensional analysis, and spatial imaging, to dissect human virus-specific T cell responses residing in the diseased tissues in great detail. We are particularly interested in the immune responses of virus-specific T cells in SARS-CoV-2 vaccination and infection, chronic hepatitis B virus (HBV) infection and HBV-associated liver diseases,  and human papillomavirus (HPV)-associated cancers.


Research Topics

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.

JRNLclub talk

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 memory T cells upon viral infection or vaccination (e.g., SARS-CoV-2 and HBV) in barrier or mucosal tissues during 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.


Honor

2018         Presidential Award, best oral presentation, Asia-Pacific Association for Study of Liver.

2017         The best poster prize, Hepatitis B Foundation.

2016         Travel Fellowship, 5th NIF Winter School on Advanced Immunology & IFReC symposium.

2013         Singapore International Graduate Award (SINGA) Fellowship, A*STAR.

2012         Thesis Award for MSc , University College London.


Educational Background
  1. Massachusetts General Hospital/Harvard Medical School, Senior Research Scientist. 2020-2023.
  2. Singapore Immunology Network (A*STAR), Postdoctoral Research Fellow. 2017-2020.
  3. Singapore Immunology Network (A*STAR) & Nanyang Technological University, Singapore, PhD, SIgN-NTU joint program.  2013-2017.
  4. Division of Infection and Immunity, University College London, London, United Kingdom, MSc, Infection and Immunity program. 2011-2012.
  5. Department of Microbiology, Soochow University, Taipei, Taiwan, BSc in Microbiology. 2002-2006.

2 Vacancies

Job Description

OVERVIEW

The Cheng lab (https://thechenglab.com/) is looking for an enthusiastic and excellent Research Technician to join our dynamic and competitive group in human immunology research in the Institute of Biomedical Science at Academia Sinica, Taiwan. Our research focuses on deep-profiling human virus-specific T cells during viral infection, vaccination, or virus-associated cancer by using highly multiplexed combinatorial peptide-MHC tetramer staining, mass cytometry, and single-cell sequencing methods (Cheng et al., 2019. Science Immunology; Cheng et al., 2021. Immunity), and high-dimensional analysis (Newell and Cheng., 2016. Nature Immunology). We are interested in dissecting the different arms of human adaptive immune responses, and characterize their functional and cellular heterogeneity, particularly tissue-resident memory T cells and follicular helper T cells. We are currently working on chronic hepatitis B infection (HBV), HBV-associated hepatocellular carcinoma and liver disease, and SARS-CoV-2 infection and vaccination.

RESPONSIBILITIES

  1. Learn mass cytometry and/or spectral flow cytometry.
  2. Handling and processing clinical samples.
  3. Single-cell sequencing methods and analysis.
  4. Data analysis.

Preferred Intern Education Level

Undergrad, BSc, or MSc.

Skill sets or Qualities

  • Passionate in science
  • Great organization and communication (verbal and writing) skills
  • Team player with great interpersonal characteristics