Gene Regulation, Stems Cells and Cancer

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Epigenetics Events in Cancer



GROUP LEADER:
Luciano Di Croce (ICREA Research Professor)
POSTDOCTORAL FELLOWS:
Lluis Morey, Luigi Aloia (until August 2014) Malte Beringer, Pedro Vizan, Enrique Blanco, Gloria Mas, Sergio Beltran (from June 2014)
PhD STUDENTS:
Payal Jain, Alexandra Santanach, Andreas Lakner (shared with Thomas Graf)
MASTER STUDENT:
Anna Alcaine (from September 2014)
TECHNICIANS:
Arantxa Gutierrez, Cecilia Ballare

Summary

Embryonic stem (ES) cells have the potential to both renew indefinitely in culture, and to differentiate into every cell type of the body. Both processes, self-renewal and differentiation, are governed by transcriptional activation or repression of the relevant genes. Polycomb proteins play a key role in regulating ES cell fate and differentiation. Mechanistically, they function within multiprotein complexes, called Polycomb repressive complexes (PRCs), which modify histones (and other proteins) and silence target genes. On the other hand, Polycomb proteins are often misregulated in human cancers.

Therefore, the research in our group is focused on the characterization of the role of key components of the Polycomb complex (including novel interactors) in regulating gene expression, stem cell differentiation, chromatin compaction and carcinogenesis processes.


Research Projects

  • Variations in the composition of PcG complexes during mESC differentiation
  • Role of PCL proteins in mESC differentiation and cancer
  • Characterization of novel interactors of Polycomb complexes
  • Role Zrf1 in the establishments and maintenance of neural progenitor identity

Selected Publications

Rocha-Viegas L, Villa R, Gutierrez A, Iriondo O, Shiekhattar R, and Di Croce L.
“Role of UTX in RAR-mediated Gene Regulation in Leukemia.”
Mol Cell Biol, 34:3765-75 (2014).
This manuscript is highlighted in: Spotlight: Mol Cell Biol, 34:3559.

Aloia L, Di Stefano B, Sessa A, Morey L, Gutierrez A, Cozzuto L, Benitah SA, Graf T, Broccoli V, and Di Croce L.
“Zrf1 is required to establish and maintain neural progenitor identity.”
Genes & Develop, 28:182-97 (2014).

Aguilar H, Urruticoechea A, Halonen P, Kiyotani K, Mushiroda T, Barril X, Serra-Musach J, Islam A, Caizzi L, Di Croce L, … , and Pujana M.
“VAV3 mediates resistance to breast cancer endocrine therapy.”
Breast Cancer Res, 28:R53 (2014).

Caizzi L, Ferrero G, Cutrupi S, Cordero F, Ballaré C, Miano V, Reineri S, Ricci L, Friard O, Testori A, Corà D, Caselle M, Di Croce L, De Bortoli M.
“Genome-wide activity of unliganded Estrogen Receptor α in breast cancer cells.”
PNAS, 111:4892-7 (2014).

Demajo S, Uribesalgo I, Gutiérrez A, Ballaré C, Capdevila S, Roth M, Zuber J, Martín-Caballero J, Di Croce L.
“ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia.”
Oncogene, 33:5501-10 (2014).