• Metabolic reprogramming of CD8+T cells in chronic inflammatory diseases
• Immune dysregulation in inflammation-driven cancers
• The impact of maladaptation to systemic metabolic dysregulation on anti-tumor immunity

• Research Associate, Department of Immunology and Inflammation, Imperial College London
• Ph.D., Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
• MPhil, Department of Surgery, The University of Hong Kong
• B.Sc., (Hons), Department of Biochemistry, The University of Hong Kong

Metabolic reprogramming of CD8+T cells in chronic inflammatory diseases: Sustained inflammation causes immune cell dysfunction and forms the common pathological basis for many chronic inflammatory diseases including chronic viral infection, cancer and autoimmunity. A key aspect of immune cell dysfunction that underpins the clinical outcome of these chronic conditions is the development of exhausted CD8+T cells. Nonetheless, reasons for CD8+T cell exhaustion remain incompletely understood. Our laboratory employs the emerging technologies from the field of immunometabolism to assess the effects of sustained inflammation on exhausted T cell differentiation as well as the implications of tumor-immune coevolution on the efficacy of cancer immunotherapy. Our long-term goal is to develop metabolism-targeting drugs to regulate T cell immunity in infection, cancer and autoimmunity. 

Immune dysregulation in inflammation-driven cancers: Immune cells act as a double-edged sword in cancer. While CD8+T cells drive anti-tumor responses and form the basis of cancer immunotherapy, innate immune cells like neutrophils are often reprogrammed by the tumor microenvironment into pro-tumorigenic cells that antagonize tumor-killing immune responses. Our lab employs multi-omics and preclinical models to unravel the drivers of neutrophil heterogeneity and pro-tumor neutrophil formation. We aim to specifically target pathogenic neutrophils while preserving the conventional neutrophil population essential for host defence.

The impact of maladaptation to systemic metabolic dysregulation on anti-tumor immunity: Type 2 diabetes (T2D) is the leading non-communicable disease worldwide characterized by hyperglycemia (HG). Notably, cancer patients with T2D often experience poor prognosis and resistance to immunotherapy, suggesting that immunosurveillance is compromised by this underlying condition. Using patient samples and various cancer models, our group investigates how aberrant adaptations to HG imprint intrinsic defects in immune cells, diminishing their anti-tumor capabilities. This highly translatable knowledge will lead to better preventive and therapeutic strategies against cancer in T2D patients.

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3. Gray V#, Chen WX#, Tan RJY, Teo JMN, Huang Z, Fong CH, Law TWH, Ye Z, Yuan S, Bao X, Hung IFN, Tan KC*, Lee CH*, Ling GS*. Hyperglycemia-triggered lipid peroxidation destabilizes STAT4 and impairs anti-viral Th1 responses in Type 2 Diabetes. Cell Metabolism 2024 Vol36 DOI: 10.1016/j.cmet.2024.10.004
4. Campbell C, Funk M, Hattori Y, Hu W, Jeschke J, Lau C, Ling GS, Liu S, Llorens-Rico V, Nemes E. Women in STEM becoming independent: The journey to independence is an immensely gratifying odyssey. Journal of Experimental Medicine 2024 Vol 221 (7):e20240842
5. Chen WX, Teo JMN, Yau SW, Wong WMM, Lok CN, Che CM, Javed A, Huang Y, Ma S, Ling GS. Chronic Type I interferons signaling promotes lipid peroxidation-driven terminal CD8+T cell exhaustion and curtails anti-PD-1 treatment efficacy. Cell Reports 2022 Vol 41:111647 doi: https://doi.org/10.1016/j.celrep.2022.111647
6. Lee CH#, Gray V#, Teo JMN, Tam AR, Fong CHY, Lui DTW, Chan KH, Hung IFN*, Tan KCB*, Ling GS*. Comparing the B and T Cell-mediated Immune Responses in Patients with Type 2 Diabetes Receiving mRNA or Inactivated COVID-19 Vaccines. Frontiers in Immunology 2022 13:1018393. #Joint first author
7. Ye ZW, Ong CP, Tang K, Fan Y, Luo C, Zhou R, Luo P, Cheng Y, Gray V, Wang P, Chu H, Chan JFW, To KKW, Chen H, Chen Z, Yuen KY, Ling GS*, Yuan S*, Jin DY*. Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 confers sterilizing immunity in animals. Cellular & Molecular Immunology 2022 Vol 19:588-601.
8. Buang N, Tapeng L, Gray V, Sardini A, Chad W, Lightstone L, Cairns T, Pickering M, Behmoaras J,  Ling GS*, Botto M*. Type I interferons affect the metabolic fitness of CD8+T cells from patients with systemic lupus erythematosus. Nature Communications 2021 12:1980 doi: 10.1038/s41467-021-22312-y.
9. Ling GS, Crawford G, Buang N, Bartok I, Tian K, Thielens NM, Bally I, Harker JA, Ashton-Rickardt PG, Rutschmann S, Strid J, Botto M. C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism. Science 2018 Vol 360:558-563.
10. Bulla R*, Tripodo C*, Rami D*, Ling GS*,Agostinis C, Guarnotta C, Zorzet S, Durigutto P, Botto M, Tedesco F. C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation. Nature Communications 2016 Feb 1;7:10346. doi: 10.1038/ncomms10346.
11. Ling GS, Bennett J, Woollard KJ, Szajna M, Fossati-Jimack L, Taylor PR, Scott D, Franzoso G, Cook HT, Botto M.Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages. Nature Communications 2014;5:3039. doi: 10.1038/ncomms4039

• RGC ECS 2020/2021 (PI)
• RGC GRF 2021/2021 (PI)
• RGC GRF 2022/2023 (PI)
• RGC GRF 2023/2024 (PI)
• RGC GRF 2024/2025 (PI)
• RGC GRF 2025/2026 (PI)
• HMRF 2019 (PI)
• HMRF 2024 (PI)

• Topic editor (Cellular and Molecular Gastroenterology and Hepatology 2024 -)
• The Department of Medicine teaching award, Imperial College London (2015)

Rachael Tan (Mphil student 2025-)

Qingyang Ge (PhD student 2025-)

Yalei Lui (Mphil student 2025-)

Zhulin Chen (Mphil student 2023-)

Weixin Chen (RPG research assistant; PhD student 2021-)

Qier Gao (Research assistant)

Samantha Wong (Lab technician)

Past lab members:

Victor Gray (PhD graduate 2020-2024; Current position: Post-doc at Institute of Cancer Research, London)

Nickolas Teo (PhD graduate 2020-2024; Current position: Post-doc at National University of Singapore)