PhD project: Unraveling metabolic targets for potentiating CD8+ T cell function in metastatic melanoma

Katholieke Universiteit Leuven

Belgium

July 11, 2021

Description

PhD project: Unraveling metabolic targets for potentiating CD8+ T cell

function in metastatic melanoma

(ref. BAP-2021-452)

Last modification : Thursday, June 3, 2021

Research in the Lab of Metabolic Regulation of Cell Function (Department of Cellular and Molecular Medicine) focuses on unraveling the metabolic cross- talk between immune cells and cancer cells in metastatic cancer. Targeting metabolic pathways central to T cell function has the potential to restore immune balance in metastatic sites and thus combat metastatic spread. Notably, metabolic therapy can synergize with immunotherapy strategies and result in more effective cancer treatments. Our research is both of fundamental and translational nature.

Responsibilities

Metastatic melanoma represents a highly deadly disease with a 10-year survival rate of less than 10%. Activation of the endogenous immune system through immunotherapy has become a standard of care and has greatly improved treatment. Drugs that induce T cell responses against tumor-associated antigens have led, in many cases, to the specific targeting and killing of tumor cells. Yet, especially in metastatic sites, a significant subset of tumors can inhibit T cell effector function and evade the immune system. Indeed, the tumor microenvironment (TME) seems to represent a hostile niche that inhibits the function of infiltrating T cells and transforms them into an inactive exhausted state. Recently, metabolic reprogramming has emerged as a key hallmark of immune responses. To support their proliferation and survival, activated T cells use fuels to generate precursors required for macromolecular synthesis, energy, stress response, and other pro-survival pathways. As cancer cells possess a hyperactive metabolism needed to fuel their unrestricted proliferation, depletion of nutrients and an accumulation of metabolic waste products might represent a major nutritional hurdle for infiltrating T cells.

This study aims to map the metabolic requirements of T cells within the TME, develop strategies to potentiate T cell metabolism within this hostile niche, and thus use metabolic therapy to reactivate exhausted T cells and drive their cytotoxic function in immunocompromised metastasis. This project has the potential to open a new avenue of combinatorial treatment based on both immunotherapy and metabolic intervention to enhance the efficacy of immunotherapy and transform the standard of care for metastatic melanoma.

Profile
  • You obtained a Master degree in Biomedical Sciences, Medicine, Biochemistry, Bioengineering or Biology.
  • You are highly motivated, critical and creative.
  • You are willing to work with animals (mice); previous mice experience is a plus.
  • You can work independently but are also a team player.
  • You have an excellent knowledge of English, spoken and written.
  • Prior metabolomics experience is a plus.
  • Offer
  • You can do state-of-the-art, innovative research in an emerging scientific field.
  • You will get excellent guidance and supervision.
  • You will be stimulated and supported to integrate your own research ideas and goals within the project.
  • You can collaborate with several other national and international research teams, allowing you to broaden your scientific knowledge and network.
  • You will get a 1-year-PhD fellowship that is conditionally extendable up to 4 years; additional application for a personal PhD fellowship is strongly encouraged.
  • In principle, the start date of the PhD is 1 October 2021, but this is flexible in joint consultation with your supervisor.
  • Interested?

    For more information please contact Prof. dr. Ilaria Elia, tel.: +32 16 19 42 53, mail: ilaria.elia@kuleuven.be. Please include a detailed CV, a motivation letter, and the contact information of two referees.

    KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be.