This report summarizes the activities of the Institute of Biomedical Research Alberto Sols (IIBM) during the last two years. The Institute is organized into four departments aimed to tackle relevant problems in biomedicine. They are focused in the study of cell communication, metabolism regulation and its impact in the immune response, as well as in the cancer field and the nervous system associated pathologies. During 2017-18, we elaborated a new strategic plan identifying our strengths, but certainly more importantly, our weaknesses and threats. The IIBM is a research center that integrates professionals and students supported by the Autonomous University of Madrid (from the Department of Biochemistry and Molecular Biology, Faculty of Medicine) and the Spanish National Research Council. This combination of members from both organizations provides a significant capacity to adapt to changing administrative circumstances, in a synergistic way. The IIBM is a member of the Campus of International Excellence UAM+CSIC, which provided support to locate in our Institute the facilities for research, using biomedical imaging.
Regarding our internal structure, one of the topics of discussion from the last years was the necessity to enhance the collaboration between groups of the four departments. This analysis may help to reorganize the research activity, from the present structure of departments and mainly individual groups, to an intermediate level of coordination incorporating these individual groups into larger teams that can add value to this internal collaboration as well as to set common objectives of interest in the immediate years.
In addition to the researchers of the IIBM, I will express the recognition to the administration team, coordinated by Isabel Ocaña, the executive manager of the Institute. I will also recognize the dedication of the personnel in charge of the different scientific core facilities of the Institute that have shown a deep professionalism in their activities, with a positive collaboration spirit with all the researchers, especially the young recruited scientists.
We are also happy for our recent young incorporations to the Institute that have shown a commitment with the Institute, both from the University and from CSIC.
Finally, I would like to express my gratitude and recognition to the Vice-director of the Institute, Dr Aurora Sánchez Pacheco that has contributed greatly to both the cohesion of the groups and the collaboration in the management activities.
Malignant tumors develop from normal cells through complex processes with multiple stages. The laboratories of the Cancer Biology Department investigate the genes and molecular mechanisms involved in the initiation, development and progression of malignant tumors. In order to discover new biomarkers for diagnosis, prevention and therapeutic intervention in cancer, it is necessary to identify the molecular alterations by which normal cells acquire the tumor phenotype and the biological principles underlying tumor metastasis. The research conducted in the department has a strong translational vocation, as it is aimed to produce effective treatment and prevention strategies for many different types of cancer, one of the leading causes of death in developed countries.
Our researchers study of the main types of tumors affecting our society, including colon, breast, prostate, pancreatic and lung cancers. In addition, they also investigate key oncogenic processes such as epithelial-mesenchymal transition and angiogenesis. A great deal of effort is also devoted to understanding the molecular mechanisms by which tumor cells develop resistance to anti-tumor drugs with the ultimate aim of developing new, more effective treatments. This research requires a multidisciplinary approach that combines the use of animal models, cellular and molecular biology and computational biology. Lastly, there are numerous scientific collaborations between IIBM researchers and clinical investigators that facilitate the transfer of the basic knowledge generated into clinical practice.
Our department has incorporated new researchers during these past two years (Ricardo Sánchez, María Jesús Larriba, Wolfgang Link, Guillermo de Cárcer and Pilar Santisteban) and, currently, different research groups working on common themes are being structured to optimize coordination between laboratories with the aim of tackling more complex and ambitious projects. Among these research topics are the following:
Vitamin D and colon cancer: Alberto Muñoz, María Jesús Larriba y José Manuel González.
Cell Signaling and Cancer Therapy: Wolfgang Link, Guillermo de Cárcer, Ricardo Sánchez. Borja Belandia, Pilar Santisteban.
Tumor microenvironment and metastasis: Amparo Cano, Miguel Quintanilla, Bruno Sainz, Luis del Peso , Benilde Jiménez, Jorge Martín
Molecular Oncology: Gema Moreno, Gemma Domínguez
In the following pages, we describe some of the projects developed in the Cancer Biology Department during the years 2017-18.
Endocrine and Nervous System Pathophysiology
The research carried out by the Department of Endocrine and Nervous Systems Pathophysiology focuses on the study of these two key systems which control a great number of physiological processes and that will very often act together to regulate animal physiology.
To study how these systems operates in physiological as well as in pathological conditions, its research groups apply multidisciplinary research from molecules and cells to whole organisms providing the right expertise needed for both fundamental and translational research through the following specific research topics:
• thyroid hormones in the Central Nervous System during development and adult life;
• pathophysiology of the thyroid gland and nuclear receptors;
• regulation of the development, differentiation and function of pancreatic islets;
• signaling cascades modulated by neurotrophins and myelin formation,
• molecular basis of hearing function and the pathophysiology of hearing loss;
• mechanisms of neurodegeneration and neuroprotection taking place in the Nervous System including the identification of diagnostic markers and target molecules that will help developing new and efficient therapeutic drugs.
These topics are extremely relevant from a biomedical point of view, since they deal with fundamental physiological processes and highly prevalent pathologies with a strong social and health impact.
Metabolism and Cell Signaling
The Metabolism and Cell Signaling Program integrates studies on how organs and cells adapt and respond to biological and environmental stressors and the diseases arising from the dysregulation of these responses. Cell stressors include pathogenic insults, inflammation, ischemia, nutrient deficiency, genotoxic agents and autoantigens. Our Department focuses on both basic and translational research aiming to: a) understand how cells translate the environmental into biochemical events that trigger specific signaling and metabolic pathways, control gene activity, and modify cell behavior; b) identify potential biomarkers and molecular targets for diagnosis, prevention and therapeutic intervention of human diseases; c) identify and assess at preclinical level new therapies against different diseases, and d) develop new yeast mutants with industrial interest based on metabolic adaptations.
The Metabolism and Cell Signaling Department brings together investigators with complementary expertise in biochemistry, biotechnology, cellular and molecular biology, immunology, physiology, nanobiology and comparative medicine. Our multidisciplinary research involves the study of diseases ranging from diabetes mellitus, metabolic syndrome, heart failure and Parkinson's disease to autoimmunity, inflammation-driven diseases and cancer. Our goal is to provide new insights and therapeutic avenues for combating these major human diseases.
The department of Metabolism and Cell Signaling has a strong translational vocation which is reflected in patent applications and multiple collaborations with biotechnology and biomedical companies.
The department is structured in three major research areas embracing different laboratories with complementary goals, aiming to promote collaborations and to maximize resources. These areas are:
Physiopathology of the immune system: Susana Alemany, Lisardo Bosca, Victor Calvo, Antonio Castrillo, Alicia González Martín, Manuel Izquierdo and Juan Manuel Zapata
Complex diseases: Juan Jose Aragon, Carmen Delgado, Jose Gonzalez Castaño, Paloma Martin Sanz, Oscar Martinez Costa, Angela Martinez Valverde and Maria Monsalve.
Metabolism of yeasts: Carlos Gancedo
A brief description of the research performed by the members of the Department in 2017 and 2018 is provided in the following pages.
Experimental Models of Human Disease
The development of experimental models of the different human diseases is one of the bases of the present progress in medical sciences. These models allow the study of the molecular bases of the diseases and are of paramount importance for the search and testing of new drugs and treatments. The development of these models is the common goals of the research that takes place in our Department. The models systems used and the diseases studies are diverse. Among the diseases are mitochondrial-related pathologies, neurodegenerative, cardiovascular, muscular, bone diseases and syndromes, telomere-related diseases and cancer. Some of diseases studied are of very low prevalence and are considered rare diseases. Besides these basic studies, an important part of our work is translational and focused on the attention to the patients. For example, genetic studies on patient samples aimed to the molecular diagnosis of several diseases are carried out. These clinically oriented studies are made in collaboration with several Hospitals of the Spanish sanitary system.
Human clinical samples and cell lines are used for these studies together with experimental models such as mice, Drosophila melanogaster, Saccharomyces cerevisiae or Dictyostelium dicoideum. These studies have allowed the identification of new therapeutic targets, molecules with possible pharmaceutical application and biomarkers.
The Department is presently formed by 16 tenured scientists. Among the research topics are the following:
• Cardiac electrophysiology (Carmen Valenzuela, Teresa Gonzalez)
• Neurodegenerative diseases (Ana Perez-Castillo)
• Mitochondrial biogenesis and physiopathology (Miguel Fernandez Moreno, Juan José Arredondo, Rafael Garesse)
• Bone and muscular hereditary diseases and ciliopathies (Victor Ruiz and Francesc García Gonzalo)
• Telomere-related diseases (Rosario Perona, Isabel Sanchez- Perez, Leandro Sastre)
• Protein trafficking and degradation (Olivier Vincent, Ricardo Escalante)
• Tumor microenvironment and metastasis (Francisco Portillo, Pilar Eraso, María Jesús Mazón,together with Amparo Cano, of the Cancer Department)
- Department of Pathophysiology Endocrine and Nervous System
- Department of Metabolism and Cell Signaling
- Department of Experimental Models of Human Disease