Genomic Instability in Human Pathology & Aging

Current lab members:
  • Pr Hervé TECHER, CPJ (UniCA)
  • Dr Samira Kemiha, IE/Lab manager (UniCA)
  • Camille Laberthonnière, IE/Research assistant (UniCA)
  • Lorena Rejon, AI/Lab assistant (UniCA)
  • Estelle Ghibaudo, Master 1 intern (UniCA)
  • Cariss Hilal, Master 2 intern (Lebanese University)
Lab Alumni:
  • Mateo Grognet, L3 intern (Université de Nimes) 2025
  • Karim Hawillo, Master 2 Intern (Lebanese University) 2024

Cancer, increasingly recognized as an age-associated disease, exhibits common molecular traits with aging, such as genomic instability and inflammation. Our research focuses on elucidating the complex interplay between these phenomena, with a special emphasis on the exonuclease TREX1 that controls the level of cytosolic DNA and subsequent sensing and inflammatory signaling mediated by the cGAS-STING pathway. Key areas of research:

  • Exploring the DNA Replication Stress/Inflammation Loop: We aim at understanding the feedback loop connecting DNA replication stress (RS) and inflammatory signaling in different senescence contexts (induced by oncogenes, by replication stress, or by inflammation). Investigate the consequences on genome stability, senescence, and more. This research is crucial as it sheds light on the mechanisms underlying emerging cancer therapies targeting the cGAS-STING pathway.
  • Deciphering TREX1 Truncation in Pathophysiology: We aim at unravelling the mysteries behind the C-terminal truncation of TREX1 and its link to retinal vasculopathy with cerebral leukoencephalopathy (RVCL). We will explore how TREX1 mis-localization may contribute to DNA damage, genomic instability, and senescence, opening new avenues for therapeutic interventions.
  • Understanding the contribution of TREX1 to genome maintenance: We and others showed that TREX1 deficiency can lead to DNA damage and chromosomal instability, but the molecular mechanism and its impact on pathological conditions is not yet understood. This research is important to advance our knowledge on auto-inflammatory disorders and the mechanisms that maintain genome stability.

Current Projects

Top Publications

  • Transcription-Replication Conflicts and Incomplete Replication as a Cause of Micronuclei-Driven Chromoanagenesis
    par Hervé Técher
    Cancers are characterized with altered genomes. Sequencing of thousands of cancer genomes has led to the identification of new types of complex genomic rearrangements that generate new chromosomes, known as chromoanagenesis. Chromothripsis is, to-date, the best characterized phenomenon of complex rearrangements, in which a single chromosome pulverization is followed by reassembly of broken DNA fragments in a random manner. Chromothripsis and chromothripsis-related events predominantly stem from…
  • Oncogenic RAS in Cancers from the DNA Replication Stress and Senescence Perspective
    par Hervé Técher
    Rat Sarcoma (RAS)-driven cancers have been one of the main foci in the field of cancer science for over four decades. Despite significant improvement in understanding the biology of RAS oncogene, the method to target RAS-mutated cancers is still unclear. In recent years, the role for RAS beyond its hyperproliferation has been extensively documented. In this review, we systematically address and dwell on the details of the mechanisms of RAS oncogene-mediated alteration in the DNA replication and…
  • MRE11 and TREX1 control senescence by coordinating replication stress and interferon signaling
    par Hervé Técher
    Oncogene-induced senescence (OIS) arrests cell proliferation in response to replication stress (RS) induced by oncogenes. OIS depends on the DNA damage response (DDR), but also on the cGAS-STING pathway, which detects cytosolic DNA and induces type I interferons (IFNs). Whether and how RS and IFN responses cooperate to promote OIS remains unknown. Here, we show that the induction of OIS by the H-RAS^(V12) oncogene in immortalized human fibroblasts depends on the MRE11 nuclease. Indeed, treatment…
  • T-Rex escaped from the cytosolic park: Re-thinking the impact of TREX1 exonuclease deficiencies on genomic stability
    par Hervé Técher
    The Three Prime Repair Exonuclease 1 (TREX1) has been implicated in several pathologies characterized by chronic and inborn inflammation. Aberrant innate immunity caused by DNA sensing through the cGAS-STING pathway has been proposed to play a major role in the etiology of these interferonopathies. However, the molecular source of this DNA sensing and the possible involvement of TREX1 in genome (in)stability remains poorly understood. Recent findings reignite the debate about the cellular…

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Research Projects

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Research Teams

IRCAN has a diverse research teams, tackling a wide range and resolution of topics in ageing and cancer.