Regulation of Cell Growth Laboratory

This group starts as a joint initiative between Inbiomed and Instituto Oncologico de Gipuzkoa to create a multidisciplinary team foused on translational research in breast cancer stem cells.

Principal Investigator

Dr. Angel García Martín
agmartin@inbiomed.org

Dr. Angel Garcia Martin obtained his Ph.D. in 1999 at the Universidad Autonoma de Madrid and the Centro de Biología Molecular Severo Ochoa under the supervision of Prof. Manuel Fresno Escudero. His work focused on transcriptional regulation of T cell activation by citokines.

In 2000 he moved to the National Cancer Institute at Frederick (NIH; USA) for postdoctoral training in oncogene induced apoptosis in the laboratory of Dr. Howard Fearnhead. In this period Dr. Garcia Martin was interested in biochemistry of caspase activation and genomic analisis of apoptosis resitance to genotoxic stress.

Dr. Garcia Martin returned to Spain in 2005 as investigator for the genomic regulation of cancer group at Centro de Investigación Príncipe Felipe, Valencia. In 2006 he moved to the Bilbao area to work as a senior researcher at Proteomika SL developing reasearch dedicated to cancer biomarker discovery using proteomic analysis of cancer patient derived body fluids.

In March 2007 he joined Inbiomed to start the Regulation of Cell Growth Laboratory. His main research interest is to understand the role of stem cells in cancer through characterization of cancer initiating cells in order to find novel therapeutic and diagnostic/prognostic targets.

Scientific interest

This is a new research line created in 2007 investigating aspects of stem cell biology that may impact the use of stem cells in therapy. Stem cells are an excellent source of replacement cells for degenerative disorders such as osteoporosis, artritis or vascular degeneration as well as the basis for future therapies of monogenic diseases such as muscular distrophy or hemofilia. However their self-renewing capacity is at the same time a risk for their use in cell therapy as it can lead to tumour formation. Besides it will be neccessary to ensure sufficient cell survival in order for the therapy to be effective, which in some cases would have to be the rest of the patient's life.

Therefore it is relevant to understand the mechanisms that control stem cell growth and proliferation to design therapies that are safe and effective. These mechanisms involve control of cell proliferation, cell cycle, postitive and negative growth signal transduction, niche interaction as well as senescence and apoptosis. This line of reserch will stablish synergies with the other disease oriented lines as some of these processess are found altered.

The great fenotypical and molecular similarities found between adult stem cells and a minority of cells found in natural tumours responsible for the initiation, mantainance and expansion of tumors (the cancer stem cells) has lead to the suggestion that the alteration of the mechanisms that control proliferation in stem cells are at the root of cancer. These cancer stem or cancer initiating cells are the only cells in tumours that retain permanent replicative potential as well as are able to derive all the cell types found in the original tumour in vivo. Therefore we are studying cancer stem cells to understand the growth and regulation of stem cells.

We are using breast cancer stem cells isolated from natural breast tumours to characterize the alterations present in the mechanisms that control growth compared to normal mammary stem cells in order to find what are the key points relevant in their transformation.

Breast cancer is the most frequent cancer in women making up to 20% of all tumours diagnosed in women, with 1 million new cases diagnosed every year worldwide (16,000 new cases only in Spain). Worlwide it causes over 350,000 deaths with an increasing tendency. Breast cancer stem cells show the phenotype CD44+/CD24low/-Lin- though only a fraction of this population has the capacity to initiate tumours. Therefore a complete and precise description of the breast cancer stem cells is lacking.

The focus of this laboratory is to identify, isolate and culture breast cancer stem cells from natural breast tumours and compare at the molecular level with normal mammary stem cells. This research involves the stablishment of both in vitro and in vivo functional assays and the molecular characterization (both genomic and proteomic) of breast cancer stem cells to define the mechanisms responsible for its transformed phenotype.

Staff

Postdocs students
Olatz Leis Esnaola
Yolanda Sánchez Delgado

PhD students
Arrate Eguiara Fernández-Rivera

Technitians
Izaskun Beloqui
Andrés Pavón

Summer Students
David Chastrek
Erika López Arribillaga
Jone Bargiela

Publications

Jim O'Prey, Diane Crighton, Angel G. Martin, Karen H. Vousden, Howard O. Fearnhead and Kevin M. Ryan 2010 p53-mediated induction of Noxa and p53AIP1 requires NF-KB Cell Cylce 9 (5) in press.
Eguiara, A.; Leis, O.; Sánchez, Y.; Beloqui, I.; Elorriaga, K.; Rezola, R.; Martin, AG. 2009 Looking for the Cell of Origin of Cancer Clinical and Translational Oncology in press.
Martín, A.G.*; Trama, J; Crighton, D.; Ryan, K.M.; Fearnhead, H.O.; 2009 Activation of p73 and induction of Noxa by DNA damage requires NF-kappa B Aging, 1(3): 335-347. *corresponding author. Comment by K. Vousden on Aging 1(3) 275-277
Sánchez-Valdepeñas, C.; Punzón, C.; San-Antonio, B.; Martin, A.G.; Fresno, M. 2006 Cellular Signalling. 19(3):528-37.
Dhyan Chandra; Shawn Bratton; , Maria D. Person; Yanan Tian; Angel G. Martin; Mary Ayers; Howard Fearnhead; Varsha Gandhi and Dean Tang 2006 Cell, 125 (7), 1333-1346.
Sánchez-Valdepeñas, C.; Martín, A.G.; Parameswaran Ramakrishanan; Wallach, D. and Fresno, M. 2006 J. Immunol. 176:4666-4674.
G Malet, A G Martín, M Orzáez, M J Vicent, I Masip, G Sanclimens, A Ferrer-Montiel, I Mingarro, A Messeguer, H O Fearnhead and E Pérez-Payá; 2005 Cell Death and Differ. 2006 Sep;13(9):1523-32. Epub 2005 Dec 9.
Martín, A. G.; Nguyen, J.; Wells, J.; Fearnhead, H.O.; 2004 Biochem. Biophys. Res. Comm. 319: 944 -950
Martín, A. G. and Fearnhead, H.O.; 2002 J. Biol. Chem 277(52), 50834-50841.
Martín, A. G.; SanAntonio, B.; and Fresno, M; 2001 J. Biol. Chem 276(19), 15840-15849.
Martín, A. G. and Fresno, M; 2000 J. Biol Chem, 275(32), 24383-24391
Laín de Lera, T.; Folgueira, D.; Martín, A. G.; 1999 Dargemont, C; Pedraza, M.A.; Bermejo, M.; Bonay, P.; Fresno, M.; Alcamí, J.; Oncogene 18, 1581-1588.
Muñoz-Fernández, M.A.; Navarro, J.; García Martín, A.; Punzón, C.; Fernández-Cruz, E.; Fresno, M.; 1997 J. Allergy and Clin. Immunol. 100:838-45.
Muñoz-Fernàndez, M.A.; González, E.; Navarro, J.; García Martín, A.; Punzòn, C.; Fernández-Cruz, E.; Fresno, M.; 1997 Pub. of SEISIDA 8 (4), 237-241.