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Immunometabolic regulation of macrophages in glioblastoma

  • Doctorate
  • Winter
  • With scholarship

Project description

Glioblastoma (GBM) are the deadliest tumors in adults despite optimal treatment, with an average survival of <15 months upon diagnosis and a recurrence rate > 90%. Two GBM characteristics underlie such poor prognosis: 1) the infiltrative capacity of tumor cells outside of the hypoxic tumor core and 2) the unique composition of the tumor immune microenvironment (TME) that is sparce in T lymphocytes and natural killer (NK) cells but dominated by microglia- and monocyte-derived macrophages (>75% of all leukocytes in the tumor). Further, despite being part of the current standard of care, two clinical practices might contribute to GBM progression, recurrence and the dismal success of immunotherapies in this cancer: a) surgical resection that fails to eliminate infiltrative cells but elicits an inflammatory and immunosuppressive trauma with a potential to promote recurrence and b) the use of the anti-inflammatory corticosteroid, i.e. dexamethasone, aimed at countering cerebral edema but that might limit anti-tumor immunity. Macrophages are at the center of these events as they can exert both pro- and anti-inflammatory functions. Their phenotypes and functions are determined by their ontogeny and by metabolic and “danger” signals in their environment. However, their diversity in GBM post-resection and which pathways drive their functions in GBM primary growth and post-resection recurrence remain largely unknown. We use single cell and spatial transcriptomics to address the role of specific danger sensors such as the inflammasomes, in immunosuppression, cerebral edema, and anti-tumor immunity.

The objectives of this doctoral project are therefore to:

  • Characterize the impact of lactate gradients and other metabolites on the phenotypes and functions of tumor-associated microglia, monocytes and macrophages in the GB.
  • Identify and target lactate receptors and/or effectors altering the anti-tumor capacities of myeloid cells

Research fields

  • Immunology
  • Cell and Molecular Biology

Research Supervisor

Study Program

This project will be conducted as part of a PhD in Biology doctorat en biologie or Immunology doctorat en virologie et immunologie.

Requirements

Hold a master’s degree in immunology, biology, biochemistry, pharmacology, or a related field. Be open to collaborating with an interdisciplinary team and working in different areas of research.· Have a curious, resourceful and autonomous mind. 

Knowledge or experience in some or all of the following areas would be an asset:       

  • Cellular and molecular biology
  • Animal handling
  • Flow cytometry
  • Immunofluorescence
  • Bioinformatics

Financial support

INRS offers attractive scholarships. Each student benefits from financial support during their graduate studies.

Location

Centre Armand-Frappier Santé Biotechnologie
531, boulevard des Prairies
Laval (Québec) H7V 1B7

Submission of application

Interested candidates can submit their applicant by using the online form below.

Please include:

  • a cover letter indicating your interest.
  • a detailed CV.
  • a record of all your academic results.
  • contact information for three people who can provide letters of recommendation

We encourage women, visible minorities, ethnic minorities, Indigenous people and people with disabilities to apply.

Published Maya Seleh - Immunometabolic regulation of macrophages in glioblastoma

Project title : Immunometabolic regulation of macrophages in glioblastoma

Curriculum vitæ (CV) *

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Academic transcript *

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Letter of interests *

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Contact information for three people who can provide letters of recommendation *

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