IGBMC : Institut de la Génétique et de la Biologie Moléculaire et Cellulaire

• Researchers

  Bill KEYES

  Muriel RHINN

• Post-Doctoral Fellows

  Matej DURIK

• PhD Students

  Daniel SAMPAIO GONCALVES

  Irène ZAPATA BODALO

• Engineers & Technicians

  Tania KNAUER-MEYER

  Jean-Luc PLASSAT

Development and stem cells

Common Mechanisms of Development, Cancer and Aging

Cellular senescence is a form of cell cycle arrest that acts a potent tumor suppressive mechanism. In addition, it can also contribute to organismal aging and stem cell decline. However, there are aspects to senescence, such as the secretion by senescent cells of growth factors, cytokines and extracellular remodeling factors (the senescence-associated secretory phenotype, or “SASP”) that suggested more complex functions for the senescent state. While investigating possible non-classical functions for senescence, we discovered cellular senescence as a normal programmed process during embryonic development. Interestingly, senescence in the embryo is mediated by the expression of p21, exhibits features of the SASP, and instructs local tissue patterning and remodeling. Subsequently, the senescent cells are removed by apoptosis and macrophage-mediated clearance. This discovery opens up exciting new avenues to unravel the biological importance of the senescence program, its role in embryonic development and patterning, and the correlations with its function in cancer and aging.

Our lab is interested in understanding the biological role and molecular mechanisms regulating cellular senescence in different contexts, including during normal embryonic development, in tissue regeneration and aging, and in tumor development.

• Current projects

  • Investigating the role of senescence during embryonic development and tissue regeneration
  • Identifying novel mediators of stem cell aging and senescence
  • Exploring the role of candidate transcription factors and chromatin modifiers in senescence, tumor development and aging

• Collaborations

• Prizes/Awards

  • Bill KEYES - Education and Research Award - Fondation Schlumberger - 2018

• News

• Publications

  • The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice.

    Ritschka B, Knauer-Meyer T, Gonçalves DS, Mas A, Plassat JL, Durik M, Jacobs H, Pedone E, Di Vicino U, Cosma MP, Keyes WM

    Genes Dev April 1, 2020 ; 34:489-494 .

  • Cellular senescence in development, regeneration and disease.

    Rhinn M, Ritschka B, Keyes WM

    Development Oct. 1, 2019 ; 146: .

  • The WHHERE coactivator complex is required for retinoic acid-dependent regulation of embryonic symmetry.

    Vilhais-Neto GC(1)(2), Fournier M(1), Plassat JL(1), Sardiu ME(2), Saraf A(2), Garnier JM(1), Maruhashi M(1)(2), Florens L(2), Washburn MP(2)(3), Pourquie O(4)(5)(6)(7)(8).

    Nat Commun Sept. 28, 2017 ; 8:728 .

  • Retinoic acid controls early neurogenesis in the developing mouse cerebral cortex.

    Haushalter C(1), Asselin L(1), Fraulob V(1), Dolle P(2), Rhinn M(3).

    Dev Biol Oct. 1, 2017 ; 430:129-141 .

  • deltaNp63alpha promotes adhesion of metastatic prostate cancer cells to the bone through regulation of CD82.

    Di Giacomo V(1)(2), Tian TV(1)(2), Mas A(1)(2), Pecoraro M(1)(2), Batlle-Morera L(1)(2), Noya L(3), Martin-Caballero J(4), Ruberte J(3), Keyes WM(1)(2)(5).

    Oncogene Aug 2017 ; 36:4381-4392 .

  • The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration.

    Ritschka B(1,)(2), Storer M(1,)(2), Mas A(1,)(2), Heinzmann F(3,)(4), Ortells MC(1,)(2), Morton JP(5,)(6), Sansom OJ(5,)(6), Zender L(3,)(4,)(7), Keyes WM(1,)(2,)(8).

    Genes Dev Jan. 15, 2017 ; 31:172-183 .

  • Developing senescence to remodel the embryo.

    Storer M(1), Keyes WM(1).

    Commun Integr Biol Oct. 31, 2014 ; 7:e970969 .

  • New insights into skin stem cell aging and cancer.

    Ortells MC(1), Keyes WM(1).

    Biochem Soc Trans Jun 2014 ; 42:663-9 .

  • Senescence is a developmental mechanism that contributes to embryonic growth and patterning.

    Storer M(1), Mas A, Robert-Moreno A, Pecoraro M, Ortells MC, Di Giacomo V, Yosef R, Pilpel N, Krizhanovsky V, Sharpe J, Keyes WM.

    Cell Nov. 21, 2013 ; 155:1119-30 .

  • ZRF1 controls oncogene-induced senescence through the INK4-ARF locus.

    Ribeiro JD(1), Morey L, Mas A, Gutierrez A, Luis NM, Mejetta S, Richly H, Benitah SA, Keyes WM, Di Croce L.

    Oncogene April 25, 2013 ; 32:2161-8 .

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