Metabolic control of cell deaths

Metabolism, cancer and immune response

Research interests

The main focus of our lab is to understand how the deregulated metabolism of cancer cells might impact their response to chemotherapy and to the anti-cancer immune response. Our laboratory mainly focuses on the study of non-Hodgkin B lymphomas. Lymphoma is a common cancer in the Western world. 90% of aggressive lymphomas originate from B-cells and are classified as diffuse large B-cell lymphomas (DLBCLs), a genetically heterogeneous group of tumors, the most common non-Hodgkin lymphomas. To date, efforts to capture the molecular heterogeneity of DLBCL have relied on gene expression profiling that has uncovered coordinate signaling and survival paradigms in distinct subsets of DLBCL. However DLBCL are also very diverse in term of their energetic status. We therefore made the hypothesis that targeting the cellular metabolism could represent an innovative way to sensitize those lymphoma cells to chemotherapies.

In cancer research, identifying a specificity of tumor cells compared to ‘normal’ proliferating cells for targeted therapy is often considered the Holy Grail. Although diverse in origin, most cancer cells share characteristics including the ability to escape cell death mechanisms and the use of different methods of energy production. In the current paradigm, aerobic glycolysis is considered the central metabolic characteristic of cancer cells (Warburg effect). However, recent data indicate that cancer cells also show significant changes in other metabolic pathways. The renewed interest in the fact that cancer cells have to reprogram their metabolism in order to proliferate or resist to treatment must take into consideration the ability of tumor cells to adapt their metabolism to the local microenvironment (low oxygen, low nutrients). Understanding how a deregulated metabolism affects cells death and the immune response is very likely to bring new insights in fundamental biological processes and results in an innovative way to treat patients suffering from cancers.

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What we work on

– determine if the inhibition of the metabolism can modulate cell death and the anti-cancer immune response.

We identified that modulation of the metabolism impacts on the way the lymphoma cells are dying and on the way the immune system will recognized or not those dying cells. We are currently investigating the underlying mechanism.

 

– analyze the role of non-metabolic functions of glycolytic enzymes in oncogenesis and response to treatment.

While found overexpressed in most if not all tumors, we demonstrated that specific glycolytic enzymes have unique functions independently of their role in the metabolism. We are focused towards understanding how those functions may control tumor development and response to chemotherapies.

Last Publications

Rubio-Patiño C, Bossowski JP, Villa E, Mondragón L, Zunino B, Proïcs E, Chiche J, Bost F, Verhoeyen E, Ricci JE. Low carbohydrate diet prevents Mcl-1-mediated resistance to BH3-mimetics. Oncotarget. 2016 Sep 28.

Levy C, Fusil F, Amirache F, Costa C, Girard A, Negre D, Bernadin O, Garaulet G, Rodriguez A, Nair N, Vandendriessche T, Chuah M, Cosset FL, Verhoeyen E. Baboon envelope pseudotyped lentiviral vectors transduce efficiently human B cells and allow active factor IX B cell secretion in vivo in NOD/SCID mice. J Thromb Haemost. 2016 Sep 29

Verhoeyen E, Gomez S, Galy A, Ayuso E, Midoux P, Pucéat M, Vassaux G, Cordelier P. Twelfth Annual Meeting of the French Society of Cell and Gene Therapy. Hum Gene Ther. 2016 Jul;27(7):555-8

Team Publications