Dr. Eugenio Santos. Catedrático, Universidad de Salamanca. Lab. 01. (1) ascertaining the functional specificity -or redundancy-of the different members of the rasgene family (H-ras, N-ras, K-ras) and their nucleotide exchange regulators (GEF family members Sos1, Sos2 Grf1, Grf2). (2) understanding the molecular mechanisms involved in the participation of those Ras and GEF molecules in physiological and pathological processes such as cancer. (3) Linking structural and functional alterations of Ras and GEFs to specific clinical pathologies, in particular cancer.
Dr. Xosé R. Bustelo. Investigador Científico, CSIC. Lab 02.(1) Functional characterization of the Vav oncoprotein family, a group of signal transduction molecules that work as phosphorylation-dependent GDP/GTP exchange factors for the GTPases of the Rho/Rac family. (2) Functional analysis of specific members of Rho/Rac family of GTPases.(3)Characterization of intracellular positive and negative regulators of Rho/Rac GTPases. (4) Study of the cross-talk between cytoskeletal routes and other biological processes. (5) Characterization of the role of these signaling routes in cancer, paying attention to both intrinsic (proliferation, survival, metastasis) and extrinsic (angiogenesis, inflammatory response) pathways that affect the final fitness of tumors in vivo. (6) Characterization of the role of these signal transduction pathways in other high incidence health problems such as cardiovascular disease and the metabolic syndrome. (7) Development of new therapeutic avenues to treat those diseases using molecular targets belonging to those signaling routes.
Dr. Pedro Lazo-Zbikowski. Profesor de Investigación, CSIC. Lab. 04. (1) Identify upstream elements for each VRK protein, which are likely to be either a part of the pathway or a regulatory element. (2) Identify downstream elements of VRK proteins. This are likely to be intracellular substrates proteins of the kinases, but may also be interacting proteins. (3) Determine how VRK proteins are regulated in response to specific stimulation. This regulation may be covalent modifications of the protein, or alternatively represent regulation of gene expression. (4) Study the role of VRK proteins in the context of cell response to genetic damage either natural (estrés oxidative, luz UV) or induced (tobacco, radiation, chemotherapy). (5) Characterize and integrate VRK pathways in the context chromatin remodeling and its association to DNA response pathways, neurodegenerative diseases and stem cells.
Dr. Avelino Bueno. Catedrático, Universidad de Salamanca. Lab. 05. Regulación de procesos replicativos y del ciclo celular en levaduras. Control del inicio de la fase S en el ciclo de división celular. Regulación negativa de la proliferación celular en células animales.
Dr. Faustino Mollinedo. Profesor de Investigación, CSIC. Lab. 06. (1) Characterization and role of membrane rafts in apoptosis induction and cancer chemotherapy. (2) Functional relationship among membrane rafts and subcellular structures affecting cell fate. (3) Lipid metabolism in cancer cell development and therapy. (4) Search for novel anticancer drugs targeting cell death in tumor cells. (5) Mechanism of action of antitumor ether lipids as proapoptotic agents against cancer cells. (6) Use of additional biological systems (yeast, C. elegans) to uncover new signaling routes regulating cell death and to study the mechanism of action of anticancer drugs. (6) Inflammation and cancer relationship. (7) Role of neutrophils and arginase in cancer.
Dr. Jesús Pérez Losada. CSIC. Lab. 07. Genetic determinants of cancer susceptibility, evolution and treatment response.
Dr. Alberto Martín Pendas. CSIC. Lab. 09. The aim of our research is focused on the in vivo study of chromosome instability and its involvement in cancer, aging and infertility through the analysis of different proteins potentially affecting the segregation pathway. For this purpose we will determine in vivo, by means of the use of genetically modified mouse models developed in our laboratory, the consequences of the altered expression of proteins affecting directly the chromosome segregation pathway(cohesin and protectors of cohesin) in tumor suppression/progression and fertility We thus aim to provide new insights into the physiological and pathological role that proteins affecting the cohesin network have on cohesinopathies, carcinogenesis, and infertility through its participation in the assembly of the synaptonemal complex at the meiotic prophase as well as in the chromosome segregation machinery through its role in establishing chromosome cohesion.
Dr. Alberto Orfao. Profesor Titular, Universidad de Salamanca. Lab. 11. The general aim of this program is based on the fact that the oncogenic events that induce deregulation of cellular processes in haematological malignancies may translate into aberrant protein patterns displayed by malignant cells, which could be useful from the clinical point of view, for diagnosis, classification, prognosis evaluation and treatment monitoring in patients suffereing from haematological malignancies. In the same line, understanding of the role of the immune system on different malignancies/clonal disorders, through the analysis of the interactions between tumour cells and the immune microenvironment, could constitute the basis for novel immunotherapeutic strategies in the near future.
Dr. Isidro Sánchez-García. Investigador Científico, CSIC. Lab. 13. The elucidation of the molecular mechanisms that underlie tumor development remains a tremendous challenge for basic science, but also represents an essential step in the development of new drugs. The origin of cancer within a particular tissue is often impossible to determine, due to the advanced stages when patients enter the clinic. Our knowledge about the etiology of cancer is therefore derived from animal models that recapitulate human disease.
Dr. Rogelio González-Sarmiento. Catedrático, Universidad de Salamanca. Lab. 14. The first aim of the laboratory 14 is the characterization of molecular abnormalities in patients with familiar cancer within the program of Genetic Counseling in Hereditary Cancer supported by the Junta de Castilla y León. Within this project the laboratory is also characterizing molecular abnormalities in women with familiar breast cancer (more than 3 family members with breast or ovarian cancer) that do not carry BRCA mutations. We are also characterizing low penetration mutations in women with breast cancer under 40 years old. In colon cancer our secondary aim is to characterize the frequency of mutation in patients with colon cancer under 40 years old.
Dr. Atanasio Pandiella. Investigador Científico, CSIC. Lab. 15. Our research is centered in the understanding of the role of several receptor tyrosine kinases and their signal transduction routes in cell proliferation. Interest in the activation of RTKs by membrane anchored ligands has been a major focus of our laboratory with special emphasis on the study of the mechanisms responsible for the solubilization of membrane-anchored growth factors, and the biological properties of these factors in the membrane-anchored conformation.
Dr. José María de Pereda. Investigador Científico, CSIC. Lab. 17. Our group is interested in understanding at atomic level the function of proteins involved in tumoral processes. Specifically, one of our main interests focuses on the role in the assembly and regulation of cell adhesion complexes of two types of proteins: Research Team (2005-2011) the integrin family of cell adhesion receptors and the plakin family of cytolinkers. In addition, we study proteins involved in signaling processes, such as guanine nucleotide exchange factors of small GTPases and protein-phosphatases. By elucidating the atomic 3D structures of these proteins and the macromolecular complexes that they participate in, we aim at understanding their functions. Our results will pave the way to a rational structure-base design of small molecules that may alter the function of these proteins, thus having a potential therapeutic usage.
Dr. Felipe X. Pimentel Muiños. Investigador Científico, CSIC. Lab. 18. To understand the signaling events governing the apoptotic communication between the endoplasmic reticulum and mitochondria. To investigate the mechanisms that mediate cytochrome c release from apoptotic mitochondria in the absence of the conventional Bak and Bax-dependent pathway. To identify the signaling mechanisms utilized by a novel membrane molecule previously cloned in the laboratory as able to induce autophagic death. To elucidate the potential of this molecule to act as a tumor suppressor, given the role that autophagy seems to have in this phenomenon. To functionally characterize a collection of molecules previously identified in the laboratory as capable of inducing cell death upon overexpression, with an emphasis in those able to activate atypical death pathways.
Dr. Javier De Las Rivas. Profesor de Investigación, CSIC. Lab. 19. Análisis de datos ómicos de alta densidad (microarrays, ultrasecuenciación, etc). Estudio de series de datos derivados de pacientes de cáncer, particularmente de enfermedades onco-hematológicas. Estudios ómicos sobre oncogenes y genes implicados en metástasis. Identificación y caracterización de redes funcionales de genes y proteínas (network biology), sobre todo en estados biológicos normales frente a tumorales, y exploración de dichas redes para encontrar genes causales y biomarcadores moleculares.
Dr. Juan J. Cruz. Catedrático, Universidad de Salamanca. Treatment of solid tumors, with a sustained role in the development clinical trials with new therapies, particularly related to breast cancer, lung cancer, head and neck tumors, gastrointestinal cancer, gynecologic cancer, bone tumors and testicular tumors.