CANCER FROM WITHIN: immune cells reveal insights into mechanisms of DNA recombination and tumorigenesis. Lymphocytes are unique cell types of our adaptive immune system that require multiple rounds of cell divisions during their development and, most strikingly, multiple rounds of gene rearrangements during the formation of their antigen receptors. This stepwise process puts their genome integrity in danger. Quoting the hemato-oncologist Louis Staudt “normal lymphocyte differentiation is, in some sense, a disaster waiting to happen”. Indeed, lymphoma and leukemia are amongst the most common human neoplastic disorders. Our major goal is to understand the mechanisms by which a lymphoid cell maintains the integrity of its DNA and prevents genomic instability and transformation. More precisely, we study the DNA recombination processes that are part of B- and T-cell development and the mechanisms and pathways that lead to lymphoid cancers.
Study of DNA double-strand break repair regulation in B cells – implication for cancer therapy
Cancer cells frequently harbor somatic mutations leading to altered DNA repair pathways. In some cases, these defects can be therapeutically exploited as these tumor cells, but not healthy cells, rely on compensatory DNA repair […]
Mechanisms and consequences of chromosomal translocations
Chromosomal translocations can promote cancer development by disrupting tumor suppressors, activating oncogenes, or generating aberrant fusion proteins. Fusion genes are frequent in cancers and are used as diagnostic and prognostic tools to classify and […]
Think tank: Cancer
The malignant transformation of cells translates into a major worldwide health, social and economic burden. Efforts to define the etiology of cancer, along with the development of new therapeutic approaches to treat them, would […]
Deciphering the Oncogenic Lesions and Pathways of B and T Cell Cancers
FROM PHYSIOLOGICAL DNA REARRANGEMENTS TO LYMPHOID CANCERS
B and T cell lymphoid cancers are among the most common human malignancies. Many factors, endogenous and exogenous, are implicated in the etiology of these disorders, but key oncogenic lesions often arise through […]
MECHANISMS OF DNA RECOMBINATION
DNA double-strand breaks (DSBs), although common, are extremely dangerous (Deriano and Roth, Annual Review of Genetics, 2013). Unlike most other DNA lesions, DSBs directly threaten genomic integrity by disrupting the physical continuity of […]
2020Repair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ., Nat Commun 2020 10; 11(1): 5239.
2019Breakage-fusion-bridge events trigger complex genome rearrangements and amplifications in developmentally arrested T cell lymphomas, Cell Rep. 2019 Jun 4;27(10):2847-2858.e4. .
2019Coordinated signals from the DNA repair enzymes PARP-1 and PARP-2 promotes B-cell development and function, Cell Death Differ. 2019 Apr 17. .
2018The immune system profoundly restricts intratumor genetic heterogeneity, Sci Immunol. 2018 Nov 23;3(29). pii: eaat1435. doi: 10.1126/sciimmunol.aat1435..
2018Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells., Nat Cell Biol. 2018 Aug;20(8):954-965. doi: 10.1038/s41556-018-0140-1. Epub 2018 Jul 18..
2018Chromosomal Translocation Formation Is Sufficient to Produce Fusion Circular RNAs Specific to Patient Tumor Cells, iScience. 2018 Jul 27;5:19-29. .
2018The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis, Front Immunol 2018;9:400.
2017Generation and CRISPR/Cas9 editing of transformed progenitor B cells as a pseudo-physiological system to study DNA repair gene function in V(D)J recombination, J. Immunol. Methods 2017 12;451:71-77.
2017[Paralogy and redundancy: maintaining genome integrity during V(D)J recombination], Med Sci (Paris) 2017 May;33(5):474-477.
2016The RAG Recombinase: Beyond Breaking, Mech Ageing Dev. 2016 Nov 15. pii: S0047-6374(16)30263-9. doi: 10.1016/j.mad.2016.11.003. [Epub ahead of print].
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