Cancer heterogeneity and hierarchies
Josep Carreras Leukaemia Research Institute
Can Ruti CampusCtra de Can Ruti, Camí de les Escoles s/n08916 Badalona, Barcelona
We are a newly-created group passionate for cellular hierarchies and cancer heterogeneity. Our laboratory studies the key signals governing stem cell and cell fate specification during malignant progression and the mechanisms by which different signaling pathways controls cell plasticity in both normal and pathological contexts. Concretely, we combine the use of murine transgenic models, human Patient-derived xenografts and 3D-organotypic cultures to unravel cellular hierarchies within tumors for better understanding cancer heterogeneity.
Our ultimate mission is contributing to improve the treatment of choice of cancer patients by searching for novel therapeutic strategies.
Cancer is a heterogeneous disease and our projects propose the use of different mouse and human models to deeply examine this heterogeneity.
In the era of the next generation sequencing, we focus our research on the cellular behaviour and the interactions between different cell populations using in vivo and ex vivo models to reach a comprehensive picture beyond genetics based on live microscopy imaging. Certainly, we use lineage tracing strategy, now considered the most reliable approach to study cellular hierarchies and cell fate in vivo. This type of clonal analysis consists of using a genetic label to target specific cells and follow their destiny and progeny in vivo. This tool has been used to study cellular specification and evaluate stem cell potency in many tissues. In some organs, such intestine or brain, clonal analyses have proved the existence of multipotent adult stem cells able to give rise to all differentiated cell types of their tissue of origin. In others tissues, instead, there are not adult cells with multipotent capacity and their different cells types are self-maintained separately, such in the mammary gland.
We hypothesize that, the findings observed during the physiological homeostasis of the tissues, could be recapitulated or not in their respective tumors undergoing a crucial argument for understanding the tumor growth and further improving the current anti-cancer therapies. Our research will eventually explain the inefficacy of some current therapies, getting us closer to precision medicine and personalized treatments by determining the characteristics of each tumor.
We use different reporter gene strategies to monitor the expression of subpopulations within tumors and our main lines of research and specific goals are:
- Define stem cell populations and elucidate their self-maintenance
- Study the cell-of-origin of metastasis and relapse
- Characterize resistant populations to conventional therapies
- Identify new compounds for reaching personalized therapies
- Recognize key elements involved in the maintenance of the cell fate and cellular plasticity
Our group investigates the behavior of specific cellular populations in different types of cancer. Our diseases of interest so far: Breast cancer (BC), Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM)
|Verónica Rodilla||Group Leaderfirstname.lastname@example.org|
|Elena Vinuesa||PhD Studentemail@example.com|
|David Olivares Osuna||Laboratory Managerfirstname.lastname@example.org|
|Joan Balibrea||PhD Studentemail@example.com|
|Daniel Ortega||Research Studentfirstname.lastname@example.org|
|Cristina Guardia||Postdoctoral Investigatoremail@example.com|
Identification and characterization of Cardiac Glycosides as senolytic compoundsNat Commun. 2019 Oct 21 2019, 10(1):4731 .
Cellular Plasticity of Mammary Epithelial Cells Underlies Heterogeneity of Breast CancerBiomedicines. 2018 Nov 1 , 6(4) .
Manic Fringe deficiency imposes Jagged1 addiction to intestinal tumor cellsNat Commun 2018, 9(1) .
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.Genes Dev. 2015 Dec 15 , 29(24):2547-6 .
Luminal progenitors restrict their lineage potential during mammary gland development.PLoS Biol. 2015 Feb 17 , 13(2):e1002069 .
|Project leader:||Verónica Rodilla|