Gene Regulation, Stems Cells and Cancer

salvador-aznar
Epithelial Homeostasis and Cancer

Group Structure

GROUP LEADER:
Salvador Aznar-Benitah (ICREA Research Professor)
POSTDOCTORAL:
Guiomar Solanas, Patrick Welz, Alexandra Avgutinova
PhD STUDENTS:
Stefania Mejetta, Lorenzo Rinaldi
TECHNICIANS:
Gloria Pascual
STUDENTS:
Judit Serra

Summary

Adult stem cells ensure maintenance of the tissue and integrity in response to damage. They self-renew, are multipotential, and respond to and repair injuries. The skin and other stratified epithelia as model tissues display a high turnover rate, and contain well-defined populations of adult stem cells (SCs). A key feature of SCs is that they localize to specialized niches, where they remain unspecified but sense the needs of the tissue. Constant tissue replenishment drives a SCs to proliferate, the daughter cells to egress the niche, propagate, and terminally differentiate. Niche adherence, dormancy, activation, and exit, must be finely regulated processes, since loss of this tight control is causative of aging, and the onset and progression of squamous cell carcinomas.

Research Interests: Our global aim is to characterize the molecular pathways that regulate the behaviour of normal stem cells during homeostasis, and how they become deregulated during carcinogenesis and ageing.

Figure 1


Research Projects

  • What cell autonomous mechanisms regulate adult stem cell function, and how are they deregulated during ageing and cancer?
  • How do adult stem cells communicate with their local environment, and how is the system coordinated to dictate stem cell function?
  • What systemic cues communicate with adult stem cells and how do distant adult stem cells either from the same tissue or from different tissues coordinate their function at the level of the whole organism?
  • How does deregulation of pathways that control stem cell behaviour contribute to the progression of skin and oral squamous cell carcinomas (SCC)?
  • We use a combination of conditional mouse models, primary cell culture (human and mouse), live microscopy, high throughput genomics and proteomics approaches, and basic molecular biology.

Selected Publications

  1. Solanas G and Benitah SA.
    “Regenerating the skin: a task for heterogenous stem cells and their niche.”
    Nat Rev Mol Cell Biol, 14:737-48 (2013).
  2. Janich P, Toufighi K, Solanas G, Luis NM, Lehner B, Serrano L, Benitah SA.
    “Human epidermal stem cell function is regulated by circadian oscillations.”
    Cell Stem Cell, 13:745-53 (2013).
  3. Acosta JC, Banito A, Janich J, Pascual G, Athineos J, Wuestefeld T, Andrus M, Morris K, Dharmalingan G, Snijders AP, Carroll P, Capper D, Inman G, Longerich T, Sansom OJ, Benitah SA, Zender L, Gil J.
    “A complex secretory program orchestrated by the inflammasome controls paracrine senescence.”
    Nat Cell Biol, 15:978-90 (2013).
  4. Morey L, Aloia L, Cozzuto L, Benitah SA, Di Croce L.
    “RYBP and Cbx7 define specific biological functions of PRC1 complexes in mouse embryonic stem cells.”
    Cell Reports, 3:60-9 (2013).