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Immunometabolic Regulation Group

| Biography | Research Summary | Extensive Research Summary | Selected Publication List | Funding Sources | Open Positions
 

Ping-Chih Ho, Ph.D.
Assistant Professor
Department of Fundamental Oncology, University of Lausanne
Ludwig Center for Cancer Research of the University of Lausanne

E-mail: ping-chih.ho@unil.ch
Phone number: +41 (0)21 692 5947

portait ho

Biography

Ping-Chih Ho got his B.S. in Botany and M.S. in Biochemical Science at National Taiwan University in 2004 and 2006, respectively. He then decided to work as research technician in Department of Pharmacology at University of Minnesota. After one year working in Prof. Li-Na Wei’s lab as research technician, he joined Prof. Li-Na Wei’s lab as a Ph.D. student in 2008. During his Ph.D. study, he focused on transcriptional and non-transcription role of receptor-interacting protein 140 (RIP140) in adipocyte dysfunction and macrophage inflammatory regulation. In 2012, he joined Prof. Susan Kaech lab at Yale University to explore a new field of Kaech lab in cancer immunology. There, he showed that metabolic competition between cancer cells and T cells contributes to T cell dysfunction in the tumor microenvironment and further implied that nutrient restriction in tumors can be a general stress for infiltrating immune cells. In 2015 September, he was recruited at the LICR as a tenure-track assistant professor.

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Research Summary

The research focuses of Ho lab are 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-tunes immune responses in diseases, especially tumor immunity and autoimmune.

Key terms: Immunometabolic regulation, T cell, macrophage, immunotherapy, immune evasion, autoimmune.

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Extensive Research Summary

Exploiting host immunity with cancer immunotherapies to combat malignancy represents a major breakthrough for current cancer treatment. However, the instability of cancer immunogenicity and the formation of the immunosuppressive tumor microenvironment are the bottlenecks for improving the efficacy of our current immunotherapies, including checkpoint blockade and cell-based treatments. Therefore, deciphering the underlying mechanisms used by cancer cells to evade immune surveillance is direly needed.

Similar to cancer cells, activated effector T cells and pro-inflammatory antigen-presenting cells engage metabolic switch, including aerobic glycolysis and glutaminolysis, to use nutrient differentially, a process that modulates the inflammatory responses and tumoricidal activity of these immune cells. However, whether the metabolic regulation contributes to homeostasis of host immune responses and if abolishing metabolic homeostasis in tissues could lead to diseases progression remain largely unclear. We recently showed that cancer cells dampen anti-tumor immunity by competing nutrients, especially glucose, with tumor infiltrating immune cells. Importantly, metabolic rewiring tumor-specific T cells could improve metabolic fitness and anti-tumor responses of these T cells in tumors. These findings provide proof-of-concept evidence that metabolic competition between cancer cells and the surrounding cells can be a critical event for establishing an immunosuppressive tumor microenvironment. Moreover, our findings also indicate that a better understanding on the mechanistic link between metabolic activity and immune responses in immune cells could lay a platform for genetic and nutritional control of immune responses. In our lab, we have five main research themes that aim to address those unexplored questions:

  1. Metabolic regulation in myeloid cell activation and tissue homeostasis
  2. Metabolic regulation in T cell differentiation and exhaustion
  3. Immunoengineering and nutritional control for cancer immunotherapy and autoimmune
  4. Exploring the contribution of immune surveillance on instructing metabolic advantages of cancer cells
  5. Metabolic disguise of cancer stem cells that allows them to evade immune destruction

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Selected Publication List

RESEARCH ARTICLE

*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).

*John P. Ray, *Matthew M. Staron, *Justin A. Shyer, Ping-Chih Ho, Heather D. Marshall, Simon M. Gray, Brian J. Laidlaw, Koichi Araki, Rafi Ahmed, Susan M. Kaech, and Joe Craft (2015) The interleukin-2/mTOR axis designates the reciprocal signaling, differentiation, and metabolism of T helper 1 and follicular helper T cells. Immunity 43; 690-702. * is co-first author.

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).

Ping-Chih Ho, Yao-Chen Tsui, Xudong Feng, David R. Greaves, and Li-Na Wei (2012) NF-kB-mediated degradation of the co-activator RIP140 regulates inflammatory response and contributes to endotoxin tolerance. Nat. Immunol. 13; 379-386.

Ping-Chih Ho, Yi-Wei Lin, Yao-Chen Tsui, Pawan Gupta, and Li-Na Wei  (2009) A negative regulatory pathway of GLUT4 trafficking in adipocyte: new function of RIP140 in the cytoplasm via AS160. Cell Metab. 10; 516-523.

REVIEWS/COMMENTARIES

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

Ping-Chih Ho* and Susan M. Kaech* (2017) Reenergizing T cell anti-tumor immunity by harnessing immunometabolic checkpoints and machineries. Current Opinions in Immunol. (Under review). *is corresponding author.

Tung Chao, Haiping Wang, and Ping-Chih Ho (2017) Mitochondrial control and guidance of immune responses of innate and adaptive immune cells. Frontiers. in Immunol. (Under revision).

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

Ping-Chih Ho*, Pu-Ste Liu (2016) Metabolic communication in tumors: a new layer of immunoregulatoion for immune evasion. Journal for ImmunoTherapy of Cancer 4; 4-12. * is corresponding author.

BOOK CHAPTERS

Ping-Chih Ho and Li-Na Wei (2012) Nuclear receptor-interacting protein 140. Encyclopedia of Signaling Molecules

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Funding Sources

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SNSF       

Swiss Cancer League

Melanoma Research Alliance

Society of Immunotherapy for Cancer

Roche

Actelion

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Open Positions

If you are interested in our research and would like to join our lab as Postdoctoral researchers (with training background in immunology, cell biology or cellular metabolism) or PhD student, please send email to ping-chih.ho@unil.ch for further information regarding position opening.

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