grupo

Group name: Gene Expression Regulation & Cancer

    Group leader
  • Pedro Medina Vico
  • Postdoctorals
  • Maria Isabel Rodríguez Lara
  • PHD Students
  • Isabel Fernández Coira
  • Paola Peinado Fernández
  • Carlos Baliñas Gavira
  • Joel Martín Padrón
  • Associate Researchers
  • Marta Cuadros Celorrio
  • Internships
  • Álvaro Andrades Delgado

RESEARCH AREAS

GENE EXPRESSION REGULATION increases the functional versatility and adaptability of the cell by allowing it to express certain proteins when needed. It is, therefore, one of the most important and complex processes of biology. Changes in the gene expression patterns are key in cancer cell transformation, through an increase in expression of genes that promote carcinogenesis (oncogenes) and/or a decrease in expression of genes that prevent it (tumour suppressor genes). MicroRNAs (miRNAs) and chromatin-structure both play important roles in this process and have been found to be critical in the development of human pathologies. Both of these regulatory elements, especially in the context of CANCER, have been the focus of my interest during my career.

The SWI/SNF complex is an ATP-dependent chromatin-remodelling complex that is known to regulate EPIGENETICALLY the gene expression (Kwon, Imbalzano et al. 1994). Increasing evidence demonstrates that some components of the SWI/SNF complex are tumour suppressors and are involved in human cancer development. One subunit of this complex, SNF5, is inactivated in malignant rhabdoid tumours (MRTs) and heterozygous Snf5 knockout mice develop tumours that are histologically similar to human MRTs (Roberts, Galusha et al. 2000; Roberts, Leroux et al. 2002). BRG1 (Medina and Sanchez-Cespedes 2008), the helicase/ATPase catalytic subunits of the SWI/SNF complex, is mutated in many different cancer cell lines (Wong, Shanahan et al. 2000; Medina, Romero et al. 2008). Additionally, germline BRG1 mutations linked to a Rhabdoid Tumour Predisposition Syndrome was reported in a family, strongly suggesting that is a bona fide tumour suppressor gene (Schneppenheim, Fruhwald et al.). Recently, it has been discovered that two other subunits of the chromatin-remodelling complex, BAF250 (ARID1A) and BAF180 (PBRM1) (Jones, Wang et al. ; Wiegand, Shah et al. ; Varela, Tarpey et al. 2011; Wilson and Roberts 2011), are frequently mutated in ovarian clear cell carcinoma and renal carcinoma, respectively. All these observations support an important role of the SWI/SNF complex in cancer, however its specific function is still unclear.

MiRNAs are a recently discovered class of small RNA molecules that regulate gene expression at the post-transcriptional level. Due to their small size and unusual nature, miRNAs were not discovered in humans until 2000. Today, over one thousand miRNAs have been identified in the human genome. Aberrant biogenesis and/or expression of miRNAs have been linked to human diseases including cancer (Medina and Slack 2008). During my training as a postdoc in this field I have helped to reveal the critical role played by specific miRNAs in cancer. While most previous studies in the field used cell lines or in vitro systems, we pioneered the functional study of the role of miRNAs using in vivo transgenic mouse models. We demonstrated the therapeutic utility of let-7 microARN ectopic expression in vivo (Medina, Trang et al. 2010), and the important of a single microARNs (miR-21) to the drive of tumor development (Medina, Nolde et al. 2010). In my recently created group at the GenyO Center we will continue unveiling the role of the microRNAs in cancer with the hope to find novel and useful cancer therapies.

FUNDING

  • 7º Programa Marco de la Comunidad Europea.
  • Programa Nacional de Proyectos de Investigación Fundamental no Orientada.
  • Junta de Andalucía
  • Consejería de Salud de la Junta de Andalucía
  • Campus of International Excellence of BioHealth, Information Communications and Technology.
  • Fundación BBVA
  • Fundación Inocente Inocente
  • Deutsche JC Leukämie-Stiftung

SELECTED PUBLICATIONS

10. Coira IF, Rufino-Palomares EE, Romero OA, Paola Peinado, Chanatip Metheetrairut, Boyero-Corral L, Carretero J, Farez-Vidal E, Cuadros M., Reyes-Zurita F, Lupiáñez JA, Sánchez-Cespedes M., Slack FJ. Expression inactivation of SMARCA4 by microRNAs in lung tumors.  Medina PP2015 Mar 1;24(5):1400-9. doi:10.1093/hmg/ddu554. PMID: 25355421.

Los resultados de este trabajo han sido destacados o comentados por diversos artículos de revistas del sector, entre los que se incluyen:

  • Genética Médica News | Vol. 2 | Núm. 21 | 2015, pág 18-19.

9. Schiaffino-Ortega S, Baliñas C, Cuadros M, Medina P.P. SWI/SNF proteins as target in cancer therapy. Journal of Hematology & Oncology 2014, 7:81 J Hematol Oncol. 2014 Nov 13;7(1):81. PMID: 25391308.

Catalogado como Highly accessed article al recibir más de mil visitas en menos de un mes tras su publicación. Ha sido el artículo más visitado de la revista durante 2014.

8. Rufino-Palomares EE, Reyes-Zurita FJ, Lupiáñez JA, Medina PP. MicroARNs as oncogenes and tumor Suppressors. Chapter #14 of the Book “MicroRNAs in Medicine” edited by Charles H. Lawrie. ISBN: 978-1-118-30039-8. Wiley Ed. January, 2014.

7. Muñoz-Lopez M, Medina PP, Garcia-Perez JL. Wiping methylation: Wip1 regulates genomic fluidity on cancer. Cancer Cell. 2013 Oct 14;24(4):405-7. PMID: 24135277

6. Palma P, Cuadros M, Conde-Muñoz R, Olmedo C, Cano C, Segura-Jimenez I, Blanco A, Bueno P, Ferron JA, Medina P. Microarray Profiling of Mononuclear Peripheral Blood Cells Identifies Novel Candidate Genes Related to Chemoradiation Response in Rectal Cancer. PLoS One. 2013 Sep 5;8(9), PMID: 24040155.

5. Chen PY(*), Qin L(*), Barnes C, Charisse K, Yi T, Zhang X, Ali R, Medina PP, Yu J, Slack F, Anderson DG, Kotelianski V, Wang F, Tellides G, Simons M. FGF regulates TGFβ signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression. Cell Reports 2, 1–13, December 27, 2012. PMID: 23200853. (*) Contribución equivalente.

4. Medina P.P., Mona Nolde and Frank J. Slack. "OncomiR addiction in an in vivo model of microRNA-induced pre-B cell lymphoma". Nature. 2010 Sep 2;467(7311):86-90. PMID: 20693987

Artículo galardonado con el Premio en Investigación Básica del Yale Cancer Centre (Edición 2010).

Clasificado en entre el 2% de los artículos más significativos en Biología y Medicina por “Faculty of 1000 “ (un servicio analítico post-publicación “peer review”). http://f1000.com/6381959

            Los resultados de este trabajo han sido destacados o comentados por diversos artículos de reconocidas revistas del sector, entre los que se incluyen:

  • MicroRNAs As Onco-miRs, Drivers of Cancer (PMID: 20739651; Journal of the National Cancer Institute).
  • Research Highlights (Nature Reviews Cancer; September 2010, VOL 10 Number 9),
  • The Meaning of 21 in the MicroRNA World: Perfection Rather than Destruction (PMID: 20832748, Cancer Cell Volume 18, Issue 3, 203-205).
  • miRNA Addiction Depending On Life’s Little Things (PMID: 20869610; Current Biology).
  • MicroRNA Gene Added to 'Elite List' of Critical Cancer Genes (BioWorld, August 10th, 2010).

3. Trang P. (*) ; Medina PP. (*), Wiggins JF, Ruffino L, Kelnar K, Omotola M, Homer R,  Brown D, Andreas G. Bader, Joanne B. Weidhaas and Slack FJ. Regression of murine lung tumors by the let-7 microRNA. Oncogene. 2010 Mar 18;29(11):1580-7. PMID: 19966857

2. Medina PP, Castillo SD, Blanco S, Sanz-Garcia M, Largo C, Alvarez S, Yokota J, Clevers HC, Cigudosa JC, Lazo PA, Sanchez-Cespedes M. The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in lung cancer. Human Molecular Genetics 2009 Apr 1;18(7):1343-52. PMID: 19153074.

1. Medina PP, Slack FJ. Blocking miRNAs in vivo. Nature Methods. 2009 Jan;6(1):37-8. PMID: 19116612.

ADDITIONAL INFORMATION

My UGR website link: http://www.ugr.es/~pedromedina