Current lab members:

• Chloé FERAL (DR2 Inserm)
• Soline Estrach (CRHC) CRCN INSERM 2011
• Etienne Boulter postdoc CRCN
• Laetitia Seguin postoc CRCN
• Manon Durandy (LLCC, UCA )
• Charles-Maxime Vivier (MRT)
• Sarah Kunz (CIFRE Sanofi)
• Laurence Cailleteau, IECN Inserm

Lab Alumni:

• Chaïma BEDOUI
• Ines KRAWCZYK
• Justine TEYTU
• Laure MUNOZ
• Paula PERESSINI
• Quentin FERRARI

Our research explores how aging affects the regeneration of epithelial tissues—like the skin, intestine, and lungs—and their progression into cancer using models ranging from mice to cellular systems. The intestine and skin frequently renew themselves, while the lungs regenerate very slowly. These tissues interact extensively with the external environment, facing significant mechanical forces that they sense and respond to at various levels. We focus particularly on how cells convert mechanical signals into biological responses during tissue regeneration. Understanding the aging process’s impact on this and stem cell behavior could lead to breakthroughs in promoting healthier aging and designing targeted cancer therapies tailored to individual needs.

Current Projects

Top Publications

• ECM and epithelial stem cells: the scaffold of destiny
  4 avril 2024 par Soline Estrach
  Adult stem cells play a critical role in maintaining tissue homeostasis and promoting longevity. The intricate organization and presence of common markers among adult epithelial stem cells in the intestine, lung, and skin serve as hallmarks of these cells. The specific location pattern of these cells within their respective organs highlights the significance of the niche in which they reside. The extracellular matrix (ECM) not only provides physical support but also acts as a reservoir for…
• NANOBODY^® Molecule, a Giga Medical Tool in Nanodimensions
  9 septembre 2023 par Sarah Kunz
  Although antibodies remain the most widely used tool for biomedical research, antibody technology is not flawless. Innovative alternatives, such as Nanobody^(®) molecules, were developed to address the shortcomings of conventional antibodies. Nanobody^(®) molecules are antigen-binding variable-domain fragments derived from the heavy-chain-only antibodies of camelids (VHH) and combine the advantageous properties of small molecules and monoclonal antibodies. Nanobody^(®) molecules present a small…
• The biophysical property of the limbal niche maintains stemness through YAP
  24 avril 2023 par Swarnabh Bhattacharya
  The cell fate decisions of stem cells (SCs) largely depend on signals from their microenvironment (niche). However, very little is known about how biochemical niche cues control cell behavior in vivo. To address this question, we focused on the corneal epithelial SC model in which the SC niche, known as the limbus, is spatially segregated from the differentiation compartment. We report that the unique biomechanical property of the limbus supports the nuclear localization and function of…
• Fibroblast growth factor-2 bound to specific dermal fibroblast-derived extracellular vesicles is protected from degradation
  22 décembre 2022 par Isabelle Petit
  Fibroblast growth factor-2 (FGF2) has multiple roles in cutaneous wound healing but its natural low stability prevents the development of its use in skin repair therapies. Here we show that FGF2 binds the outer surface of dermal fibroblast (DF)-derived extracellular vesicles (EVs) and this association protects FGF2 from fast degradation. EVs isolated from DF cultured in the presence of FGF2 harbor FGF2 on their surface and FGF2 can bind purified EVs in absence of cells. Remarkably, FGF2 binding…
• Lung Adenocarcinoma Tumor Origin: A Guide for Personalized Medicine
  12 avril 2022 par Laetitia Seguin
  Lung adenocarcinoma, the major form of lung cancer, is the deadliest cancer worldwide, due to its late diagnosis and its high heterogeneity. Indeed, lung adenocarcinoma exhibits pronounced inter- and intra-tumor heterogeneity cofounding precision medicine. Tumor heterogeneity is a clinical challenge driving tumor progression and drug resistance. Several key pieces of evidence demonstrated that lung adenocarcinoma results from the transformation of progenitor cells that accumulate genetic…
• The LEGO® brick road to open science and biotechnology
  22 mars 2022 par Etienne Boulter
  LEGO® is a brand of toys that have entertained generations of children. Beyond amusement, LEGO® bricks also constitute a building ecosystem of their own that creators from the general public, as well as scientists and engineers, can use to design and assemble devices for all purposes, including scientific research and biotechnology. We describe several of these constructions to highlight the construction properties of LEGO® and their advantages, caveats, and impact in biotechnology. We also…
• Cyclic uniaxial cell stretching in tissue culture using a LEGO®-based mechanical stretcher and a polydimethylsiloxane stretchable vessel
  26 avril 2021 par Etienne Boulter
  Mechanical signals are essential for the regulation of many biological processes. Therefore, it has become paramount to account for these mechanical parameters when exploring biological processes. Here, we describe a protocol to apply cyclic uniaxial stretch on cells in culture using a LEGO®-based mechanical stretcher and a flexible custom-made polydimethylsiloxane culture vessel as well as validated downstream applications. While this system offers an out-of-the-box limited type of simulation,…
• A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy
  29 janvier 2021 par Laetitia Douguet
  Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates…
• Cyclic uniaxial mechanical stretching of cells using a LEGO^® parts-based mechanical stretcher system
  12 décembre 2019 par Etienne Boulter
  Mechanical cues are essential for the regulation of cell and tissue physiology. Hence, it has become an utmost necessity for cell biologists to account for those mechanical parameters when investigating biological processes and they need devices to manipulate cells accordingly. Here, we report a simple mechanical cell-stretching system that can generate uniaxial cyclic mechanical stretch on cells in tissue culture. This system is based upon a low-cost battery-powered uniaxial cyclic mechanical…
• Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states
  31 juillet 2019 par Marianne Stemann Andersen
  The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating^(1,2). Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cell fate…
• Cell metabolism regulates integrin mechanosensing via an SLC3A2-dependent sphingolipid biosynthesis pathway
  20 novembre 2018 par Etienne Boulter
  Mechanical and metabolic cues independently contribute to the regulation of cell and tissue homeostasis. However, how they cross-regulate each other during this process remains largely unknown. Here, we show that cellular metabolism can regulate integrin rigidity-sensing via the sphingolipid metabolic pathway controlled by the amino acid transporter and integrin coreceptor CD98hc (SLC3A2). Genetic invalidation of CD98hc in dermal cells and tissue impairs rigidity sensing and mechanical signaling…
• Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy
  9 octobre 2018 par Thomas Bertero
  Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism promotes tumor aggressiveness by sustaining the activity of key growth, invasion, and survival pathways. Yet mechanisms by which biophysical properties of ECM relate to metabolic processes and tumor progression remain undefined. In both cancer cells and carcinoma-associated fibroblasts (CAFs), we found that ECM stiffening mechanoactivates glycolysis and glutamine metabolism and thus coordinates non-essential amino…
• Personalized medicine: exploiting druggable vulnerabilities for KRAS-driven lung cancer
  24 juillet 2018 par Laetitia Seguin
  No abstract
• ¹⁸F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L
  1 décembre 2016 par Chloé C Feral
  CONCLUSIONS: We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce ^(18)F-FDOPA uptake.
• The body's tailored suit: Skin as a mechanical interface
  28 juillet 2016 par Floriane S Tissot
  Skin, by nature, is very similar to the Rouquayrol-Denayrouze suit mentioned by Jules Verne in Twenty Thousand Leagues Under the Sea: it allows "to risk (…) new physiological conditions without suffering any organic disorder". Mechanical cues, to the same extent as other environmental parameters, are such "new physiological conditions". Indeed, skin's primary function is to form a protective barrier to shield inner tissues from the external environment. This requires unique mechanical properties…
• Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability
  7 mars 2016 par Laura R de la Ballina
  CD98hc functions as an amino acid (AA) transporter (together with another subunit) and integrin signaling enhancer. It is overexpressed in highly proliferative cells in both physiological and pathological conditions. CD98hc deletion induces strong impairment of cell proliferation in vivo and in vitro Here, we investigate CD98hc-associated AA transport in cell survival and proliferation. By using chimeric versions of CD98hc, the two functions of the protein can be uncoupled. Although recovering…
• Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts
  16 décembre 2015 par Jean Albrengues
  Carcinoma-associated fibroblasts (CAF) mediate the onset of a proinvasive tumour microenvironment. The proinflammatory cytokine LIF reprograms fibroblasts into a proinvasive phenotype, which promotes extracellular matrix remodelling and collective invasion of cancer cells. Here we unveil that exposure to LIF initiates an epigenetic switch leading to the constitutive activation of JAK1/STAT3 signalling, which results in sustained proinvasive activity of CAF. Mechanistically, p300-histone…
• CD98hc (SLC3A2) loss protects against ras-driven tumorigenesis by modulating integrin-mediated mechanotransduction
  1 octobre 2014 par Soline Estrach
  CD98hc (SLC3A2) is the heavy chain component of the dimeric transmembrane glycoprotein CD98, which comprises the large neutral amino acid transporter LAT1 (SLC7A5) in cells. Overexpression of CD98hc occurs widely in cancer cells and is associated with poor prognosis clinically, but its exact contributions to tumorigenesis are uncertain. In this study, we showed that genetic deficiency of CD98hc protects against Ras-driven skin carcinogenesis. Deleting CD98hc after tumor induction was also…
• LIF mediates proinvasive activation of stromal fibroblasts in cancer
  27 mai 2014 par Jean Albrengues
  Signaling crosstalk between tumor cells and fibroblasts confers proinvasive properties to the tumor microenvironment. Here, we identify leukemia inhibitory factor (LIF) as a tumor promoter that mediates proinvasive activation of stromal fibroblasts independent of alpha-smooth muscle actin (α-SMA) expression. We demonstrate that a pulse of transforming growth factor β (TGF-β) establishes stable proinvasive fibroblast activation by inducing LIF production in both fibroblasts and tumor cells. In…

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