Research Projects

Hallmarks of cancer, which include dysregulation of cell cycle and apoptosis are both of tumor and of microenvironment origins. Although these hallmarks favor cancer survival and growth, they also confer specific addictions or vulnerabilities to cancer cells that can be exploited for therapies with regard to cancer heterogeneity and specificity.
We work on identifying vulnerabilities – Achille’s heel – that are consequent to the adaptation of cancer cells to survival and resistance within their ecosystem. More precisely, we focus on major molecular pathways involved in resistance/escape of cancer cells to death, such as p53 pathway and BCL2 network. We develop original culture models (ex vivo coculture models, PDX, patients’ cohorts) and cutting-edge technologies (Multispectral cytometry, scRNASeq). Our research models are mature B-cell malignancies, Multiple Myeloma and Mantle Cell Lymphoma.

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Staff

Catherine Pellat, DR CNRS
David Chiron, CR CNRS

Martine Amiot, DR CNRS
Agnès Moreau-Aubry, PU
Cyrille Touzeau, PU-PH
Marion Eveillard, MCU-PH
Benoît Tessoulin PH
Yann Le Bris, PH
Patricia Gomez- Bougie, CR
Delphine Boulet, Post Doctoral Student
Romane Durand, Post Doctoral Student

Géraldine Descamps, IE
Christelle Dousset, IE
Sophie Maiga, AI
Céline Bellanger, IE

Salomé Decombis, PhD Student
Ophélie Champion, PhD Student

Main Publications

Touzeau C, Dousset C, Le Gouill S, Sampath D, Leverson JD, Souers AJ, Maïga S, Béné MC, Moreau P, Pellat-Deceunynck C, Amiot M. The Bcl-2 specific BH3 mimetic ABT-199 : a promising targeted therapy for t(11 ;14) multiple myeloma. Leukemia. (2014)

Tessoulin B, Descamps G, Moreau P, Maiga S, Lodé L, Godon C, Marionneau-Lambot S, Ouiller T, Le Gouill S, Amiot M, Pellat-Deceunynck C. PRIMA-1Met induces myeloma cell death independently of p53 by impairing the redox balance. Blood. (2014)

Chiron D, Di Liberto M, Martin P, Huang X, Sharman J, Blecua P, Mathew S, Vijay P, Eng K, Ali S, Johnson A, Chang B, Ely S, Elemento O, Mason CE, Leonard JP, Chen-Kiang S. Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov. (2014)

Brosseau C, Dousset C, Touzeau C, Maïga S, Moreau P, Amiot M, Le Gouill S, Pellat-Deceunynck C. Vitamin D3 and lenalidomide synergize to induce apoptosis in mantle cell lymphoma via demethylation of BIK. Cell death and disease (2014)

Touzeau C, Ryan J, Guerriero J, Moreau P, Ni Chonghaile T, Le Gouill S, Richardson P, Anderson K, Amiot M, Letai A. BH3-profiling identifies heterogeneous dependency on Bcl-2 family members in Multiple Myeloma and predicts sensitivity to BH3 mimetics.” Leukemia (2015)

Gomez-Bougie P, Halliez M, Moreau P, Pellat-Deceunynck C, Amiot M. Repression of Mcl-1 and disruption of the Mcl-1/Bak interaction in myeloma cells couple ER stress to mitochondrial Apoptosis. Cancer Lett. (2016)

Chiron D, Bellanger C, Papin A, Tessoulin B, Dousset C, Maïga S, Moreau A, Esbelin J, Trichet V, Chen-Kiang S, Moreau P, Touzeau C, Le Gouill S, Amiot M, Pellat-Deceunynck C. Rational targeted therapies to overcome microenvironment-dependent expansion of mantle cell lymphoma. Blood. (2016)

Touzeau C, Le Gouill S, Mahé B, Boudreault JS, Gastinne T, Blin N, Caillon H, Dousset C, Amiot M, Moreau P. Deep and sustained response after venetoclax therapy in a patient with very advanced refractory myeloma with translocation t(11;14). Haematologica. (2017)

Tessoulin B, Eveillard M, Lok A, Chiron D, Moreau P, Amiot M, Moreau-Aubry A, Le Gouill S, Pellat-Deceunynck C. p53 dysregulation in B-Cell Malignancies: more than a single gene in the pathway to hell. Blood Reviews (2017)

Leverson JD, Sampath D, Souers AJ, Rosenberg SH, Fairbrother WJ, Amiot M et al., Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax. Cancer Discov. (2017)

Le Gouill S, Thieblemont C, Oberic L, et al., Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma. NEJM (2017)

Gomez-Bougie P, Maiga S, Tessoulin B, Bourcier J, Bonnet A, Rodriguez MS, Le Gouill S, Touzeau C, Moreau P, Pellat-Deceunynck C, Amiot M. BH3-mimetic toolkit guides the respective use of BCL2 and MCL1 BH3-mimetics in myeloma treatment. Blood 2018

Lok A, Descamps G, Tessoulin B, Chiron D, Eveillard M, Godon C, Le Bris Y, Vabret A, Bellanger C, Maillet L, Barillé-Nion S, Gregoire M, Fonteneau JF, Le Gouill S, Moreau P, Tangy F, Amiot M, Moreau-Aubry A, Pellat-Deceunynck C. p53 regulates CD46 expression and measles virus infection in myeloma cells. Blood Adv 2018

Papin A, Tessoulin B, Bellanger C, Moreau A, Le Bris Y, Maisonneuve H, Moreau P, Touzeau C, Amiot M, Pellat-Deceunynck C, Le Gouill S, Chiron D. CSF1R and BTK inhibitions as novel strategies to disrupt the dialog between mantle cell lymphoma and macrophages. Leukemia 2019

Le Gouill S, Morschhauser F, Chiron D, et al. Ibrutinib, Obinutuzumab And Venetoclax In Relapsed and Untreated Patients with Mantle-Cell Lymphoma, a phase I/II trial. Blood. 2020.

Jullien M, Gomez-Bougie P, Chiron D, Touzeau C. Restoring Apoptosis with BH3 Mimetics in Mature B-Cell Malignancies.Cells. 2020

Le Bris Y, Magrangeas F, Moreau A, Chiron D,…, Pellat-Deceunynck C, Hermine O, Delfau-Larue MH, Tessoulin B, Béné MC, Minvielle S, Le Gouill S. Whole genome copy number analysis in search of new prognostic biomarkers in first line treatment of mantle cell lymphoma. A study by the LYSA group. Hematol Oncol. 2020

Seiller C, Maiga S, Touzeau C, Bellanger C, Kervoëlen C, Descamps G, Maillet L, Moreau P, Pellat-Deceunynck C, Gomez-Bougie P, Amiot M Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes..Cell Death Dis. 2020