Epigenetics

in stem cells and cancer

A University of Granada research group led by Dr. David Landeira
at the Centre for Genomics and Oncological Research (GENYO)

Epigenomics

We use leading edge technology to study the human epigenome.

Bioinformatics

Data produced in our analysis is subjected to cutting edge bioinformatic analysis.

Biomedicine

Our long term goal is to contribute to the application of stem cells to the clinics and to personalized cancer treatment.

Research

We study the role of epigenetic heterogeneity in the biology of stem cells and cancer

We are interested in understanding how epigenetic cell-to-cell variability impacts early mammalian development and cancer progression. We use molecular and cell biology tools combined with emerging bioinformatics platforms to study key biological systems. We use embryonic stem cells (ESCs) to study the role of epigenetics in the biology of pluripotent cells and human cell lines and patient samples to study the function of epigenetic factors in cancer progression.

Epigenetic cell-to-cell variability in pluripotency

ESCs are derived from the inner cell mass of blastocysts and provide a clonally self-renewing source of pluripotent cells that retain the potential to give rise to all cell types in an adult organism. ESCs and induced-pluripotent cells hold great promise for cell replacement therapies and disease modelling. However, pluripotent cells and derived counterparts display marked phenotypic heterogeneity that hampers their safe application in clinics. Importantly, defining the molecular basis of pluripotency is also a key challenge in basic developmental biology. ESCs display fluctuating levels of key determinants of the pluripotent state. Changes in gene transcription can result in protein fluctuation and therefore epigenetic regulation is crucial in the creation of cell-to-cell variability in genetic clonal populations. However, identification of epigenetic regulators involved and their mode of action has been hindered due to technical limitations. Combination of genome-wide analysis of the epigenome with single-cell gene expression data has established that chromatin factors can regulate cell-to-cell variability in ESCs. More recent genome-wide studies of individual cells are beginning to show that gene expression and the epigenome can be highly variable in pluripotent stem cells.

Epigenetic intratumor heterogeneity

At cancer diagnose tumors are composed of tens of millions of cells that have already diversified producing heterogeneous cell populations. Intratumoral heterogeneity (ITH) has been observed in solid tumors and leukemia where it has been used to model tumor evolution and thus improving our understanding of tumorigenesis.  However a majority of cancer therapies still fail to achieve durable responses which is often attributed to underlying ITH. Genetic alterations have been traditionally identified like the main drivers of ITH. However, emerging literature show that in cell populations with high degree of genetic homogeneity, epigenetic heterogeneity can lead to cell-to-cell variability in response to therapy. Additionally, genes encoding regulators of the epigenome are among the most commonly mutated genes in different cancer types. Thus, epigenetic ITH is increasingly appreciated as a determinant of treatment failure and disease recurrence.

Currently we are developing a set of projects to depict epigenetic heterogeneity and associated chromatin regulators that is critical for pluripotency function and cancer progression. We aim to characterize novel regulatory aspects that will be key to understand early human development, to move pluripotent cells to the clinics and to develop more personalized and precise strategies in cancer treatment.

Scheme highlighting the implications of cell-to-cell epigenetic variability in the regulation of pluripotency and in cancer treatment. Top diagram shows clonal population of pluripotent cells in which epigenetic regulators promote functional heterogeneity (represented as green, blue and red cells) and thus regulate their differentiation capacity.  Bottom diagram shows a primary tumor composed by subpopulation of cells with dissimilar resistance to chemotherapy (represented as green, blue and red cells) and thus altered propensity to produce secondary tumors.

Sponsors

Who we are

We are a multidisciplinary group led by Dr. David Landeira and affiliated to the Department of Biochemistry and Molecular Biology II at University of Granada. Our lab is based at the Centre for Genomics and Oncological Research (GENYO) that is co-funded by Pfizer, University of Granada and the Andalusian Regional Government.

Technical expertise

Molecular and cell biology
Epigenomics and bioinformatics
Use of stem cells and cancer samples

We have extensive expertise using molecular and cell biology tools combined with emerging bioinformatics platforms to study key biological systems. We use embryonic stem cells to study the role of epigenetics in the biology of pluripotent cells and human cell lines and patient samples to study the function of epigenetic factors in cancer progression.

Contact

Contact Info

+34 958 715 500
davidlandeira@ugr.es
Centro de Genómica e Investigación Oncológica (GENYO)
Av. de la Ilustración 114
18016 | Granada | Spain