Current lab members:

• Eric GILSON PU-PH
• Marie-Josèphe GIRAUD-PANIS, DR2 CNRS
• Delphine BENARROCH, CRCN Inserm
• Alexandre OTTAVIANI, MCU
• Aaron MENDEZ BERMUDEZ IR Inserm
• Serge BAUWENS, IR CNRS
• Sabrina PISANO, IR Inserm
• Florentin REMOT Post-Doc CNRS
• Huong LAI, PhD
• Peipei LIN, PhD
• Romane DESHURAUD, PhD
• Rita HILMA CDD IR CNRS
• Nadir DJERBI, AI CNRS
• Francesco ABAGNALE CDD AI Inserm
• Juliette QUEGUINER CDD IE Inserm
• Irena DELGADO, Master
• Hongly RUAN, Master

Lab Alumni:

The objective of the research in Eric Gilson team is to provide further mechanisms and molecular tools that describe telomeres as nuclear integrated structures and to understand how cell fate is determined by telomere changes with application in the aging and medical fields.

Historically, the general strategy of the team is a bottom-up approach starting from the key shelterin component TRF2, addressing numerous aspects of its structure and function relationships by combining biophysical, biochemical, molecular, cellular, genetic, experimental oncogenesis and clinical studies. The team aims at applying the knowledge gained from their research on TRF2 to address general questions regarding telomere protection and signaling, replicative senescence, immunosurveillance, organismal aging and oncogenesis as well to the development of novel clinical approaches to treat cancer and to prevent age-associated pathologies.

Recently, the team decided to address the question of the relationships between telomere and aging from a different angle by asking the basic question: does evolution change the life history of species by modifying telomere biology? This is currently addressed by studying the link between telomere variation and organismal fitness using natural populations of both budding yeast (in collaboration with the Gianni Liti team) and reef-building coral, taking advantage of the current TARA-PACIFIC expedition that is sampling corals throughout the Pacific over a 2-years cruise.

Current Projects

Top Publications

• The double-edged sword of eliminating senescent cells
  25 octobre 2024 par Eric Gilson
  No abstract
• Targeting Senescence for Next-Generation Cancer Treatments
  4 avril 2024 par Eric Gilson
  Cellular senescence has paradoxical effects on cancer emergence, progression, and therapeutic response. We herein identify four lessons that emerged from studying senescence interaction with cancer and emphasize four bottlenecks in the therapeutic manipulation of cellular senescence to prevent or cure cancer.
• Telomere DNA length regulation is influenced by seasonal temperature differences in short-lived but not in long-lived reef-building corals
  1 juin 2023 par Alice Rouan
  Telomeres are environment-sensitive regulators of health and aging. Here,we present telomere DNA length analysis of two reef-building coral genera revealing that the long- and short-term water thermal regime is a key driver of between-colony variation across the Pacific Ocean. Notably, there are differences between the two studied genera. The telomere DNA lengths of the short-lived, more stress-sensitive Pocillopora spp. colonies were largely determined by seasonal temperature variation, whereas…
• Non-canonical telomere protection role of FOXO3a of human skeletal muscle cells regulated by the TRF2-redox axis
  25 mai 2023 par Maria Sol Jacome Burbano
  Telomeric repeat binding factor 2 (TRF2) binds to telomeres and protects chromosome ends against the DNA damage response and senescence. Although the expression of TRF2 is downregulated upon cellular senescence and in various aging tissues, including skeletal muscle tissues, very little is known about the contribution of this decline to aging. We previously showed that TRF2 loss in myofibers does not trigger telomere deprotection but mitochondrial dysfunction leading to an increased level of…
• Senescence-associated transcriptional derepression in subtelomeres is determined in a chromosome-end-specific manner
  16 mars 2023 par Martin Rey-Millet
  Aging is a continuous process leading to physiological deterioration with age. One of the factors contributing to aging is telomere shortening, causing alterations in the protein protective complex named shelterin and replicative senescence. Here, we address the question of the link between this telomere shortening and the transcriptional changes occurring in senescent cells. We found that in replicative senescent cells, the genes whose expression escaped repression are enriched in subtelomeres….
• Telomeres as a sentinel of population decline in the context of global warming
  10 août 2022 par Jean-François Lemaître
  No abstract
• Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence
  12 juillet 2022 par Aaron Mendez-Bermudez
  Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation…
• Telomere dysfunction is associated with dark-induced bleaching in the reef coral Stylophora pistillata
  29 septembre 2021 par Alice Rouan
  Telomere DNA length is a complex trait controlled by both multiple loci and environmental factors. A growing number of studies are focusing on the impact of stress and stress accumulation on telomere length and the link with survival and fitness in ecological contexts. Here, we investigated the telomere changes occurring in a symbiotic coral, Stylophora pistillata, that has experienced continuous darkness over 6 months. This stress condition led to the loss of its symbionts in a similar manner…
• A Novel Screen for Expression Regulators of the Telomeric Protein TRF2 Identified Small Molecules That Impair TRF2 Dependent Immunosuppression and Tumor Growth
  2 juillet 2021 par Mounir El Maï
  Telomeric repeat-binding factor 2 (TRF2) is a subunit of the shelterin protein complex, which binds to and protects telomeres from unwanted DNA damage response (DDR) activation. TRF2 expression plays a pivotal role in aging and cancer, being downregulated during cellular senescence and overexpressed during oncogenesis. Cancers overexpressing TRF2 often exhibit a poor prognosis. In cancer cells, TRF2 plays multiple functions, including telomere protection and non-cell autonomous roles, promoting…
• The Power of Stress: The Telo-Hormesis Hypothesis
  2 juin 2021 par Maria Sol Jacome Burbano
  Adaptative response to stress is a strategy conserved across evolution to promote survival. In this context, the groundbreaking findings of Miroslav Radman on the adaptative value of changing mutation rates opened new avenues in our understanding of stress response. Inspired by this work, we explore here the putative beneficial effects of changing the ends of eukaryotic chromosomes, the telomeres, in response to stress. We first summarize basic principles in telomere biology and then describe…
• Neutrophils: mediating TelOxidation and senescence
  21 avril 2021 par Maria Sol Jacome Burbano
  Cellular senescence is considered to be a major driver of aging, yet the mechanisms explaining the accumulation of senescent cells during life time remain unclear. In this issue, Lagnado et al (2021) show that neutrophils can trigger the senescence of neighboring cells by transmitting reactive oxygen species (ROS), which they normally produce to fight pathogens. The main genomic targets of the neutrophil-mediated ROS damage are telomeres, supporting an intimate interplay between telomere…
• Longevity clocks: The promoting role of telomeres?
  9 décembre 2020 par Julien Cherfils-Vicini
  Aging is an alteration of our physiological capacities that is accompanied by an increased susceptibility to develop a wide range of diseases and which determines in large part our longevity. Despite intensive research on the origin of aging, its etiology is still poorly understood. We discuss here the hypothesis that the telomere shortening, programmed to start at the end of embryogenesis in numerous tissues, couples development with aging by a time-dependent regulation of a set of…
• Long-lived post-mitotic cell aging: is a telomere clock at play?
  8 mai 2020 par Maria Sol Jacome Burbano
  Senescence is a cellular response to stress for both dividing and post-mitotic cells. Noteworthy, long-lived post-mitotic cells (collectively named LLPMCs), which can live for decades in the organism, can exhibit a distinct type of cellular aging characterized by a progressive functional decline not associated to an overt senescence phenotype. The age-related drivers of senescence and aging in LLPMCs remain largely unknown. There is evidence that an increased production of reactive oxygen…
• A public health goal: sustainable aging
  2 avril 2020 par Éric Gilson
  No abstract
• Heterochromatin replication goes hand in hand with telomere protection
  2 avril 2020 par Aaron Mendez-Bermudez
  Telomeres arose from the need to stabilize natural chromosome ends, resulting in terminal chromatin structures with specific protective functions. Their constituent proteins also execute general functions within heterochromatin, mediating late replication and facilitating fork progression. Emerging insights into the mechanisms governing heterochromatin replication suggest telomeres and heterochromatin act in concert during development and aging. They also suggest a common evolutionary origin for…
• Mitochondrial function in skeletal myofibers is controlled by a TRF2-SIRT3 axis over lifetime
  29 janvier 2020 par Jérôme D Robin
  Telomere shortening follows a developmentally regulated process that leads to replicative senescence of dividing cells. However, whether telomere changes are involved in postmitotic cell function and aging remains elusive. In this study, we discovered that the level of the TRF2 protein, a key telomere-capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the…
• Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells
  6 juillet 2019 par Julien Cherfils-Vicini
  In the context of tumorigenesis, telomere shortening is associated with apparent antagonistic outcomes: On one side, it favors cancer initiation through mechanisms involving genome instability, while on the other side, it prevents cancer progression, due to the activation of the DNA damage response (DDR) checkpoint behaving as a cell-intrinsic proliferation barrier. Consequently, telomerase, which can compensate for replicative erosion by adding telomeric DNA repeats at the chromosomal DNA…
• Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2
  20 avril 2019 par Julien Cherfils-Vicini
  Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSCs in human cancers by upregulating TRF2, a protein required for telomere stability. Specifically, we showed that the TRF2 upregulation in cancer cells has extratelomeric roles in activating the expression of a network of genes involved in the biosynthesis of heparan sulfate proteoglycan,…
• Analysis of DNA-Protein Complexes by Atomic Force Microscopy Imaging: The Case of TRF2-Telomeric DNA Wrapping
  31 octobre 2018 par Sabrina Pisano
  Atomic force microscopy (AFM) is a non-optical microscopy that enables the acquisition at the nanoscale level of a 3D topographical image of the sample. For 30 years, AFM has been a valuable tool in life sciences to study biological samples in the field of tissue, cellular and molecular imaging, of mechanical properties and of force spectroscopy. Since the early beginnings of the technique, AFM has been extensively exploited as an imaging tool for structural studies of nucleic acids and…
• TRFH domain: at the root of telomere protein evolution?
  2 décembre 2017 par Marie-Joseph Giraud-Panis
  Two articles in Cell Research focus on the structure-function relationships in the shelterin complex that binds to telomeres and is essential for their stability and functions. These studies concerning both mammalian and Schizosaccharomyces pombe proteins reveal unexpected structural conservation of a motif called TRFH (Telomeric Repeat Factors Homology) domain between several subunits in these complexes, providing a rationale for further dissection of the role of telomeres in chromosome…

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