PEBC Report - Programa de Epigenética y Biología del Cáncer

tion of distant metastasis in colon cancer that could be
used as predictive markers of chemotherapy response.
Different immunodeficient mouse models, harboring
human colorectal carcinomas grafts, have been generated.
They allow us to immortalize colorectal carcinomas
and to evaluate the role of tumor initiating cells in tumor
progression and in response to chemotherapeutic treatments.
This characterization will allow us to identify
molecular markers with predictive value in response to
treatment that could be useful in the selection of the more
personalized anti-tumor treatment and with better clinical
response.
Selected publications
Lines of Research
1. Characterization of genetic and epigenetic changes in
epidermal stem cells during aging.
Despite their relevant role in tissue homeostasis, very little
is known about the ability of adult stem cells to repair DNA
lesions and signal through the DNA damage response
(DDR) pathway or if these pathways are altered during
normal aging. We are interested in analyzing if during
aging epidermal stem cells accumulate DNA lesions and
if these lesions result from failures in DDR and chromatin
remodeling processes involved in DNA repair.
2. Isolation and characterization of tumor initiating cells from
skin carcinomas.
We aim to isolate and characterize tumor initiating cells
from human and mouse skin carcinomas in order to identify
genes responsible of the acquisition of their specific
characteristics as well as to evaluate the impact of
genomic instability during tumor growth. These studies
offer the possibility to find new potential targets to suppress
specifically the growth of these tumoral cells during
cancer development.
3. Study of role of tumor initiating cells in the response to
chemotherapy in human colorectal carcinoma.
The aim of this project is to identify genes and mechanisms
involved in chemotherapy resistance and genera-
P. Muñoz*, R. Blanco*, G. de Carcer, S. Schoeffner, R.
Benetti, JM. Flores, M. Malumbres and MA Blasco. TRF1
controls telomere length and mitotic fidelity in epithelial
homeostasis. Mol. Cell Biol. 29(6): 1608-25, 2009.
D. Huertas, R. Sendra and P. Muñoz. Chromatin dynamics
coupled to DNA repair. Epigenetics 4(1): 31-42, 2009
R. Benetti, S. Gonzalo, I. Jaco, P. Muñoz, S. Gonzalez, S.
Schoeftner, E. Murchison, T. Andl, T. Chen, P. Klatt, F. Li, M.
Serrano, S. Millar, G. Hannon and MA Blasco. A mammalian
microRNA cluster controls DNA methylation and telomere
recombination via Rbl2-dependent regulation of DNA
methyltransferases. Nature Struct. Mol. Biol. 15: 268-279,
2008.
L. Liu, M. Okuka, S.M. Bailey, P. Muñoz, C. Li, C. Wu, E.
Czerwiec, L. Sandler, A. Seyfang, M.A. Blasco and D.L.
Keefe. Telomere lengthening early in development. Nature
Cell Biol. 9(12): 1436-41, 2007.
I.Siegl, P. Muñoz, J.M. Flores, P. Klatt and M.A. Blasco.
Deficient mismatch repair improves organismal fitness and
survival of mice with dysfunctional telomeres. Genes and
Develop. 21: 2234-47, 2007.
Meier, H. Fiegler, P. Muñoz, C. Langford, M.A. Blasco, N.
Carter and S.P. Jackson. Spreading of mammalian DDR
factors studied by ChiP-chip at damage telomeres. EMBO
J. 26: 2707-18, 2007.
R. Blanco*, P. Muñoz*, J.M. Flores and M.A. Blasco. The
telomeric protein TRF2 is a potent inducer of epithelial carcinogenesis
in the absence of telomerase. Genes and
Develop. 21: 206-220, 2007.
P. Muñoz*, R. Blanco*, J.M. Flores and M.A. Blasco. XPF
nuclease-dependent telomere loss and increased DNA
damage in mice overexpressing TRF2 results in premature
aging and cancer. Nature Genet. 37: 1063-71, 2005.
P. Muñoz, R. Blanco and M.A. Blasco. Role of the TRF2
telomeric protein in cancer and ageing. Cell Cycle, 5: 718-
21, 2006.
M. Tarsounas, P. Muñoz, A. Claas, PH. Smiraldo, DL.
Pittman, MA Blasco and SC WEST. Telomere Maintenance
Requires the RAD51D Recombination/Repair Protein. Cell
117:337-347, 2004.
Cancer Epigenetics and Biology Symposium
46 28, 29 May 2009, Barcelona