Stem cells and cancer
Our research group investigates how to generate and maintain the stem cells in the hematopoietic system under physiological conditions but also how these processes are mimicked by the tumors for their perpetuation. We constantly improve our research by implementing novel technology to understand the process of normal and malignant hematopoietic development. Our research includes basic studies at the molecular level to understand cellular processes in the context of mouse models and human patients.
Our research comprises from basic biochemical research to the analysis of animal models that reproduce the pathologies of interest and allow us to study the functional relevance of new hypothesis. The ultimate goal is to confirm the importance of the findings and study possible therapeutic applications through the analysis of patient samples. In this sense we have devoted special efforts to understand the regulation of haematopoietic stem cells, as a tool to understand the mechanisms that regulate leukemia initiation and maintenance.Molecules that control both tumor initiation and progression, and tissue/stem cell homeostasis include those of the Notch, Wnt and NFκB signalling payhways. Studying these pathways in the hematopoietic, intestinal and skin tissues has also led to the identification of several interactions between them, which proved to be crucial for tissue homeostasis. We are currently working on several projects that deal with different functional aspects of normal haematopoietic stem cell regulation as well as leukemia initiating cells.
Generation of hematopoietic stem cells.
Our group was pioneer in revealing that specific elements of the Notch and Wnt/b-catenin pathways are required for the generation of hematopoietic stem cells during embryogenesis. Our current studies are focused on understanding the signals that the embryo uses to form these self-renewing cells that maintain the hematopoietic system throughout the life of the organism. We use genetically modified mouse strains combined with cutting edge imaging technologies, single cell genomics (scRNAseq, Cut&tag, ATAC seq), explant cell culture and “in mouse” hematopoietic transplantion assays to reveal how this process occurs. Our current challenge is to model the process of HSC specification in embryonic stem cells (ESC) in order to obtain functional cells for therapeutic applications.
Image 1: Hematopoietic cluster in the aorta
Understanding T Acute Lymphoblastic Leukemia (T-ALL) development and T-cell lymphoma.
We study the signals that regulate the generation and maintenance of normal and leukemic cells, as well as leukaemic stem cells (LSCS). With this aim we have developed in vitro and in vivo experimental models that complement the analysis of patient samples. In addition, we are now using several next-generation techniques to identify genetic drivers (Whole genome sequencing), gene expression patterns (RNA-seq), epigenetic patterns ( Chip-Seq or Cut&tag), CRISPR/Cas9 applications and specific multi-protein complexes (mass spectrometry) that define the populations of interest at the molecular level. These studies may reveal novel therapeutic targets for T-ALL and cutaneous T cell lymphoma (CTCL).
Image 2: Giemsa staining, leukemic blast
GATA2 deficiency syndrome
We are collaborating in an international consortium to understand the contribution of GATA2 mutations to pediatric Myelodysplastic syndrome and transformation to Acute Myeloid Leukemia (AML). We are developing humanized blood animal models of this syndrome.
Image 3: Progenitor colony (CFU-GM)
Understanding cell transformation
In addition, we work closely with the Research Group for Molecular Mechanisms of Cancer and Stemnessdirected by Dr. Lluís Espinosa and we take advantage of our discoveries in haematopoietic cells to understand epithelial tissues and vice versa. This long-standing partnership allows us to achieve a highest understanding of the biological problems and optimize resources.
Image 4: ChiP
Fundació Marató TV3
AECC (Spanish Cancer Association)
WCR (Worldwide Cancer Research).
Member of the National Cancer Network since 2008 and CIBERONC since 2017.
|Anna Bigas||Group Leaderfirstname.lastname@example.org|
|Yolanda Guillén||Postdoctoral Investigatoremail@example.com|
|Roshana Thambyrajah||Postdoctoral Investigatorfirstname.lastname@example.org|
|Violeta García||Postdoctoral Investigatoremail@example.com|
|Luis Galán||PhD Studentfirstname.lastname@example.org|
|David Arambilet||PhD Studentemail@example.com|