Immunometabolic regulation

The research focus is to decipher how nutrients affect immune responses of an array of immune cells through the unexplored metabolic regulations and to investigate how metabolic reprogramming and targeting can be harnessed to fine-tune immune responses in diseases, especially tumor immunity and autoimmune.

Metabolic adaptation of T cells

Metabolic stress imposed by the tumor microenvironment and peripheral tissues to CD8 T cells and other tissue-resident T cells challenges cellular behaviors. In this research theme, we would like to decipher how these regulations tailor T cell behavior and differentiation program by intervening signaling, epitranscripome, and proteome.

Metabolic crosstalk during immuosurveillance

Metabolic competition and communication between cancer cells and their neighboring immune cells determines the amplitude and type of immune response. In this direction, we would like to understand how this communication influence immune cell’s behavior and metabolic makeup of cancer cells uring tumorigenesis.

Firing up immune ignorant tumor

Lack of T cell infiltration in tumors represents one of the major barriers of effective cancer immunotherapy, especially checkpoint blockade. In this project, we would like to understand how we can fire up cold tumors to synergize with current immunotherapy and aim to define new types of immunotherapies for cancer treatment.

Immunometabolic regulations in macrophages

The functional plasticity of macrophages is tightly regulated by cytokines. In vivo, metabolic activities of macrophages have been revealed to play a new layer of regulation to orchestrate macrophage activities. We would like to decipher how these metabolic regulations, especially mitochondrial processes, guide macrophage activation and shape their functions in tumor and inflammatory diseases.

Exosome and immunometabolic regulations

Exosome released by dendritic cells play a critical role on guiding T cell activation. However, it remains unclear if it regulates T cell metabolism. Here, we would like to explore this and aim to exploit novel approaches for vaccine design and cancer immunotherapy.

• Ping-Chih Ho, Jessica Dauz Binhuniak, Andrew N. Macintyre, Matthew M. Staron, Xiaojing Liu, Robert Amezquita, Yao-Chen Tsui, Guoliang Cui, Goran Micevic, Jose C. Perales, Steven H. Klenstein, E. Dale Abel, Karl Insogna, Stefan Feske, Jason W. Locasale, Marcus W. Bosenberg, Jeffrey C. Rathmell, and *Susan M. Kaech (2015) Phosphoenolpyruvate is a metabolic checkpoint controlling Ca2+-NFAT signaling and anti-tumor T cell responses. Cell 162; 1217-1228. *is corresponding author. (Cover story).

• Guoliang Cui, Matthew M. Staron, Simon M. Gray, Ping-Chih Ho, Robert Amezquita, Jingxia Wu, and Susan Kaech (2015) IL7 induces TAG synthesis through the glycerol channel aquaporin 9 to sustain memory CD8+ T cell homeostasis. Cell 161; 750-761.

• Ping-Chih Ho, Katrina M. Meeth, Yao-Chen Tsui, Bhaskar Srivastava, Marcus W. Bosenberg, and Susan M. Kaech (2014) Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and IFNg. Cancer Research 74; 3205-3217. (Cover story).

• Haiping Wang, Fabien Franco, and Ping-Chih Ho (2017) Metabolic demand and guidance of regulatory T cell formation in cancer. Trends in Cancer (In press).

• Daniel E. Speiser, Ping-Chih Ho and Gregory Verdeil (2016) Regulatory circuits of T cell function in cancer. Nat. Rev. Immunol. 16; 599-611.

• ISREC
• SNSF
• Swiss Cancer League
• Melanoma research alliance
• Society of immunotherapy for cancer care
• Roche
• Actelion
• Harry J. Llyod Charitable Trust
• Anna Fuller Fund
• Cancer Research Institute-CLIP