The genetic and biological basis of tumor initiation and evolution

This research program aims at characterizing the mutational process in healthy tissues and preneoplastic disease states that predate tumorigenesis. The advent of high throughput sequencing technologies in the last decade has revealed that driver mutations work in concert with genomic, epigenomic, and epitranscriptomic alterations in the same cells. The main challenge is to integrate all this molecular information into the cellular and organismal interactions that occur between the tumor and the host and determine cancer outcome and patient survival.

    • Xosé R. Bustelo | Bustelo’s lab
    • Miguel R. Campanero | New therapeutic targets in lymphoid tumors
    • Guillermo de Cárcer | Cell cycle and cancer biomarkers
    • Francisco J. Blanco | Biomolecular NMR
    • José M. de Pereda | Structural biology of cell adhesion and signaling
    • Eugenio Santos | GTPases and cancer: RAS mediated signaling
    • Alberto Muñoz | Colon cancer: organoids, microenvironment and vitamin D
    • Ana Ortega Molina | Metabolism in cancer and aging
    • Andrés Joaquín López-Contreras | Molecular oncology and targeted therapies
    • Angela María Martínez Valverde | Physiopathology and molecular mechanisms of obesity and associated comorbidities
    • César Cobaleda | Cellular plasticity in development and cancer
    • David Santamaría | Quantitative control of RAS signalling output
    • Bruno Sainz Anding | Cancer stem cells and tumor microenvironment
    • Fernando J. Corrales | Functional proteomics
    • Aurora Gómez-Duran | MitoPhenomics lab
    • Amancio Carnero | Molocular biology of cancer
    • Emilio Lecona | Chromatin, cancer and the ubiquitin system
    • Pablo Huertas | DNA double strand break repair and human diseases
    • Fernando Monje-Casas | Cell division control
    • Isidro Sánchez-García | Stem cells, cancer stem cells and cancer biology
    • Javier Redondo Muñoz | Biomechanics of the nucleus and epigenetics during cell migration
    • Joaquin Teixidó | Immune cell migration and differentiation, and therapy resistance in cancer
    • Jose C. Reyes | Epigenetics and gene expression
    • Matthias Drosten | RAS signaling and lung cancer
    • Ricardo Pardal | Physiopathology of neural crest-derived stem cells
    • Ricardo Sanchez Prieto | Molecular basis of chemo- and radio-resistance in tumors
    • Sandra Blanco Benavente | Epitranscriptomics and cancer
    • Víctor Borrell | Neurogenesis and cortical expansion
    • Federico Mayor | GPCR signaling networks in cancer progression
    • Javier León Serrano | Transcriptional control of cancer
    • Pedro A. Lazo-Zbikowski Taracena | Regulation of epigenetic chromatin remodelling in cancer and neurodegeneration
    • Pilar Santisteban| Emerging genes in thyroid cancer
    • Aura Carreira | Genome instability and cancer predisposition
    • Piero Crespo | Spatial regulation of RAS-ERK signals in cancer
    • Andrés Aguilera | Genome instability and cancer
    • Inés María Antón | Actin cytoskeleton in tumour progression and metastasis

BUSTELO’S LAB

XOSÉ R. BUSTELO – Instituto de Biología Molecular y Celular del Cáncer

Mechanisms of cancer, signaling, driver identification, genomics, proteomics, mouse models

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NEW THERAPEUTIC TARGETS IN LYMPHOID TUMORS

MIGUEL R. CAMPANERO – Centro de Biología Molecular Severo Ochoa

To facilitate the identification of efficient therapies for lymphoid malignancies that show no undesired effects and decrease relapse frequency, we focus on genes mediating the capacity to grow in soft gels because this capacity is highly restricted to the cells that initiate tumors and facilitate tumor relapse.

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CELL CYCLE AND CANCER BIOMARKERS

GUILLERMO DE CÁRCER – Instituto de Investigaciones Biomédicas “Alberto Sols” (UAM-CSIC)

The main interest of CCCB laboratory is focused on the cell cycle and cell division machinery and how are interconnected to cancer processes. We pursue the identification of new cancer biomarkers related to cell cycle genes, with the ultimate goal to provide new tools for cancer therapy.

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BIOMOLECULAR NMR

FRANCISCO J. BLANCO – Centro de Investigaciones Biológicas Margarita Salas

We study the structure and interactions of proteins relevant in cancer: the ING proteins (chromatin remodeling and tumor suppression), the alpha subunit of G proteins (signaling and metastasis), and the PCNA and p15 proteins (DNA replication and repair), by NMR and other techniques.

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STRUCTURAL BIOLOGY OF CELL ADHESION AND SIGNALING

JOSÉ M. DE PEREDA – Instituto de Biología Molecular y Celular del Cáncer (CSIC-USAL)

We study the structural and mechanistic basis of the regulation of integrin adhesion complexes and signaling pathways that control integrin function. We aim at understanding how alterations in these cell adhesion processes may impact tumoral diseases. We use complementary methods of structural biology, biophysics, biochemistry, and cell biology.

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GTPASES AND CANCER: RAS MEDIATED SIGNALING

EUGENIO SANTOS – Centro de Investigación del Cáncer (CSIC-USAL)

Structure, function and regulation of RAS family members. Activation of cellular RAS proteins by guanine nucleotide exchange factors (Ras-GEF) of the mammalian SOS and GRF families. Mechanistic specificity/redundancy of different RAS and Ras-GEF isoforms in physiological and/or tumoral (RAS-driven) processes. SOS GEFs as biomarkers and therapy target in RAS-driven tumors.

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COLON CANCER: ORGANOIDS, MICROENVIRONMENT & VITAMIN D

ALBERTO MUÑOZ – Instituto de Investigaciones Biomédicas “Alberto Sols” (UAM-CSIC)

Our group studies human colorectal cancer (CRC). We use primary cultures of fibroblasts and stem cell-derived organoids established from healthy and tumor tissue of CRC patients to investigate the role of the Wnt/beta-catenin pathway, the contribution of the tumor microenvironment, and the antitumor action of vitamin D in this neoplasia.

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METABOLISM IN CANCER AND AGING

ANA ORTEGA MOLINA – Centro de Biología Molecular Severo Ochoa

Our lab aims to characterize the metabolic features of Double hit aggressive lymphomas using transcriptomic and metabololomic tools in preclinical models and patient samples, and screen new metabolic vulnerabilities that could be used as new targeted therapies for these lymphomas with very poor outcomes with the standard therapies.

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MOLECULAR ONCOLOGY AND TARGETED THERAPIES

ANDRÉS JOAQUÍN LÓPEZ-CONTRERAS – Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)

Genome instability is one of the hallmarks of cancer, affecting the initiation, evolution, and treatment response of the majority of cancers. To limit the accumulation of genomic alterations, cells have evolved complex mechanisms that coordinate cellular responses altogether known as the DNA Damage Response (DDR). However, in many cases the DDR is not sufficient to protect our genomes from either exogenous or endogenous insults, which may lead to cancer. The overall goal of our laboratory is to increase our knowledge on the mechanisms that regulate the DDR and to identify novel therapeutic opportunities to treat or prevent cancer.

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PHYSIOPATHOLOGY AND MOLECULAR MECHANISMS OF OBESITIY AND ASSOCIATED COMORBIDITIES

ANGELA MARÍA MARTÍNEZ VALVERDE – Instituto de Investigaciones Biomédicas “Alberto Sols” (UAM-CSIC)

Our laboratory investigates the role of key molecules that modulate insulin signaling in the progression of metabolic liver disease (NAFLD), closely linked to the worldwide obesity pandemic, which in its advanced stages can culminate in hepatocellular carcinoma (HCC). For this purpose, we have cellular models (hepatocytes, Kupffer cells, stellate cells, progenitor cells) as well as experimental models that recapitulate the different stages of NAFLD. In this context, we are studying therapeutic approaches with single or dual agonists of GLP-1 and glucagon receptors to reverse or ameliorate these pathologies avoiding their progression to advanced stages.

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CELLULAR PLASTICITY IN DEVELOPMENT AND CANCER

CÉSAR COBALEDA – Centro de Biología Molecular Severo Ochoa

We use hematopoietic development in the mouse as transgenics, knock-outs, knock-ins, constitutive and conditional) a model system to gain insight into (i) the transcriptional and epigenetic mechanisms that regulate the initiation and maintenance of cell identity, (ii) how these mechanisms are deregulated in tumorigenesis, immunodeficiencies, and genetic syndromes.

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QUANTITATIVE CONTROL OF RAS SIGNALLING OUTPUT

DAVID SANTAMARÍA – Centro de Investigación del Cáncer (CSIC-USAL)

We use mouse models and patient derived samples to characterize new oncogenic functions that participate in the onset and progression as well as in the development of drug resistance in lung adenocarcinoma. We have special interest in deciphering novel mechanisms that regulate the intensity and duration of the RAS-ERK pathway.

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CANCER STEM CELLS AND TUMOR MICROENVIRONMENT

BRUNO SAINZ ANDING – Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM)

We are running a combined basic and translation research program, which synergistically combines studies on the biology of mouse and human cancer stem cells (CSCs), including their in vivo microenvironment, in order to enhance our understanding of the regulatory machinery of CSCs.

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FUNCTIONAL PROTEOMICS

FERNANDO J. CORRALES – Centro Nacional de Biotecnología

Research on the molecular basis of liver cancer using precision proteomics tools.

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MITOPHENOMICS LAB

AURORA GÓMEZ-DURÁN – Centro de Investigaciones Biológicas Margarita Salas

MitoPhenomics research aims to decipher how genomic variation in the mitochondrial genome impacts on cellular phenotypes and identify new mechanisms involved in disease (cancer and rare diseases) and drug sensitivity, with the long-term goal of using the mitochondrial barcode as a Pharmacogenomic therapeutic tool.

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MOLECULAR BIOLOGY OF CANCER

AMANCIO CARNERO – Instituto de Biomedicina de Sevilla (IBiS)

Cancer stem cells, therapy resistance, microenvironment, senescence and immortalization.

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CHROMATIN, CANCER AND THE UBIQUITIN SYSTEM

EMILIO LECONA – Centro de Biología Molecular Severo Ochoa

Our lab is interested in understanding how DNA replication and the replication stress response are regulated by the modification of replication factors with ubiquitin and SUMO. We want to determine the alterations in these pathways that contribute to cancer development and to explore how their use as therapeutic targets.

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DNA DOUBLE STRAND BREAK REPAIR AND HUMAN DISEASES

PABLO HUERTAS – Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)

We aim to understand how the repair of DNA double strand breaks is regulated and how such regulation might impact in the appearance, development and/or treatment of several diseases, including cancer.

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CELL DIVISION CONTROL

FERNANDO MONJE-CASAS – Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)

Our research aims to shed light on the molecular mechanisms that control cell division and ensure a proper distribution of the genome during this process. Defects in chromosome segregation during mitosis can give rise to aneuploidy, an alteration of the normal karyotype that is a hallmark of cancer.

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STEM CELLS, CANCER STEM CELLS AND CANCER BIOLOGY

ISIDRO SÁNCHEZ-GARCÍA – Instituto de Biología Molecular y Celular del Cáncer (CSIC-USAL)

My research is focused on attaining a better understanding of the initiation of lymphoid tumors. Primary scientific contributions are related to the the discovery of the causal role of the exposure to infections and childhood leukemia development. These controbutions have fostered our group as a leader in this field.

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BIOMECHANICS OF THE NUCLEUS AND EPIGENETICS DURING CELL MIGRATION

JAVIER REDONDO MUÑOZ – Centro de Investigaciones Biológicas Margarita Salas

We are a group of scientists interested in understanding how epigenetic changes drive the nuclear deformability, migration and infiltration of leukemia cells.

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IMMUNE CELL MIGRATION AND DIFFERENTIATION, AND THERAPY RESISTANCE IN CANCER

JOAQUÍN TEIXIDÓ – Centro de Investigaciones Biológicas Margarita Salas

Resistance to combined BRAF/MEK inhibitors is frequent in melanoma. Drug-tolerant persisters (DTP) regenerate the tumor, but remain treatment-sensitive, offering a therapeutic window to refrain resistance. Using a mouse model of melanoma showing resistance to BRAF/MEK inhibitors we are transcriptionally and functionally characterizing DTPs. Human PDX models will validate our data.

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EPIGENETICS AND GENE EXPRESSION

JOSE C. REYES – Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)

In my group we combine genetic, molecular and computational biology methods to understand how chromatin of regulatory elements and gene bodies change during transcription, how these changes are regulated and inherited and what protein factors are responsible for them. We specially investigate how alteration of these chromatin mechanisms are implicated in epithelial to mesenchymal transition and in cancer.

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RAS SIGNALING AND LUNG CANCER

MATTHIAS DROSTEN – Instituto de Biología Molecular y Celular del Cáncer (CSIC-USAL)

Our laboratory aims at the identification and validation of novel molecular targets for the treatment of lung cancer driven by KRAS oncogenes with special emphasis on those targets that may help to overcome resistance to targeted therapies directed against KRAS or its downstream effectors.

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PHYSIOPATHOLOGY OF NEURAL CREST-DERIVED STEM CELLS

RICARDO PARDAL – Instituto de Biomedicina de Sevilla (IBiS)

We are interested in pathologies associated to the presence of neural crest-derived stem cells, such as pediatric neuroblastoma tumors. We study the molecular mechanisms used by these progenitor cells to proliferate and migrate, giving rise to tumor growth and metastases, with the aim of blocking their function and therefore improving patient survival.

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MOLECULAR BASIS OF CHEMO- AND RADIO-RESISTANCE IN TUMORS

RICARDO SÁNCHEZ PRIETO – Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM)

We studied the role of cell signalling in the cellular response to chemo and radiotherapy. Our study covers both conventional chemotherapy and new compounds used in targeted therapy. The main objective is to understand how cell signalling can be involved in the development of resistant phenotypes.

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EPITRANSCRIPTOMICS AND CANCER

SANDRA BLANCO BENAVENTE – Instituto de Biología Molecular y Celular del Cáncer (CSIC-USAL)

RNA modifications are beginning to define a novel layer of biological complexity that is becoming widely appreciated as the epitranscriptome. Our main interest is to decipher epitranscriptomic mechanisms affecting cancer. We seek to understand how RNA modifications regulate self-renewal, differentiation, growth, survival and invasion processes in normal and malignant cells.

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NEUROGENESIS AND CORTICAL EXPANSION

VÍCTOR BORRELL – Instituto de Neurociencias (CSIC-UMH)

Our laboratory investigates the basic principles of embryonic brain development, focused on the expansion and folding of the cerebral cortex and its pathological malformation, related to epilepsy and cognitive deficit. Our interest has recently shifted to pediatric brain cancers, particularly those with early onset and related to dysregulation of development.

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GPCR SIGNALING NETWORKS IN CANCER PROGRESSION

FEDERICO MAYOR – Centro de Biología Molecular Severo Ochoa

Understand the role of the complex interactomes of GPCR-related signaling nodes, such as GRK2 or Gq, in breast or stratified epithelia tumors, using cellular and mice models to characterize their deregulation by environmental or inflammatory stresses and their relationship with tumoral hallmarks, to identify new therapeutic targets

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TRANSCRIPTIONAL CONTROL OF CANCER

JAVIER LEÓN SERRANO – Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC)

The group works on  a) roles of the transcription factors MYC, MNT and CTCF in myeloproliferative syndromes, Burkitt lymphoma and T cell lymphoma (J. León and MD Delgado) and b) functional genomics of tumor development combining single cell transcriptomics and animal models of pancreatic cancer  (I. Varela).

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REGULATION OF EPIGENETIC CHROMATIN REMODELLING IN CANCER AND NEURODEGENERATION

PEDRO A. LAZO-ZBIKOWSKI TARACENA – Instituto de Biología Molecular y Celular del Cáncer

Identify and characterize the novel signaling pathways where human chromatin kinase VRK1 participates, particularly in the context of biological processes associated to cell proliferation, DNA damage responses in the tumor phenotype, and its participation in neurodegenerative syndromes such as Amyotrophic lateral sclerosis (ALS) and muscular dystrophies. We have already characterized the rare mutations in the VRK1 gene alters neuronal migration and cause a defective formation of Cajal bodies that are defective and impair functions associated to several diseases.

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EMERGING GENES IN THYROID CANCER

PILAR SANTISTEBAN – Instituto de Investigaciones Biomédicas “Alberto Sols” (UAM-CSIC)

We are identifying emerging genes and pathways in thyroid cancer. Recently we have made considerable progress in the identification of new molecules that we are currently studying in an integrative fashion. Special interest are microRNA, LncRNA and the role of RNA biogenesis and editing.

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GENOME INSTABILITY AND CANCER PREDISPOSITION

AURA CARREIRA – Centro de Biología Molecular Severo Ochoa

Mutations in BRCA2 predispose to breast and ovarian cancer with high penetrance and they are also linked to other types of cancer. BRCA2 protein is implicated in the high-fidelity DNA repair mechanism called homologous recombination. We investigate the link between defects in BRCA2 function, genome instability and cancer.

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SPATIAL REGULATION OF RAS-ERK SIGNALS IN CANCER

PIERO CRESPO – Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC)

We are interested on how subcellular localization and signal compartmentalization affect the biochemical and biological outputs of RAS-ERK pathway signals, both in physiological and pathological contexts, in particular in cancer, and how space-regulated effects can be exploited as antineoplastic strategies.

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GENOME INSTABILITY AND CANCER

ANDRÉS AGUILERA – Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)

Errors in DNA replication and repair result in cancer predisposition and genome instability (GIN). We try to identify the causes of GIN associated with cancer by deciphering how transcription-replication conflicts and mutations in RNA and chromatin factors result in GIN, to use this knowledge in cancer diagnostics and therapy.

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ACTIN CYTOSKELETON IN TUMOUR PROGRESSION AND METASTASIS

INÉS MARÍA ANTÓN – Centro Nacional de Biotecnología (CNB-CSIC)

Cell transformation and invasiveness rely on actin dynamics, controlled by neural Wiskott-Aldrich syndrome protein (N-WASP) and WIP (WASP-interacting protein). We study N-WASP/WIP role in cancer stem cell generation, progression and metastasis focusing on murine and human glioblastoma; WIP is a potential biomarker and therapeutic target for this aggressive brain malignancy.

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