Epigenetics in Stem Cells and Cancer

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Epigenetics in Stem Cells and Cancer

Dr. David Landeira

Scientific interest areas

We are interested in understanding how epigenetic factors regulate early mammalian development and cancer progression in humans. We use molecular and cell biology tools combined with genome-wide bioinformatics analysis to study key biological systems. We use pluripotent embryonic stem cells (ESCs) to study the role of epigenetics in cell plasticity and differentiation during early mammalian development. To study de role of chromatin factors in cancer progression, we combine the analysis of human cell lines and cancer patient samples.

We are a multidisciplinary group affiliated to the Department of Biochemistry and Molecular Biology II of the University of Granada.

More information: http://www.landeiralab.ugr.es

Research areas

  • 1. Epigenetic cell-to-cell variability in pluripotency.
    ESCs are derived from the inner cell mass of the developing blastocysts (E3.5 in mouse and E5.5 in humans) and provide an infinite source of pluripotent cells that retain the potential to give rise to all cell types in an adult organism. Thus, pluripotent cells are a great system to study the molecular basis of the formation of the human organism. Additionally, pluripotent cells hold great promise for cell replacement therapies and disease modelling. An important aspect of pluripotent cells is their marked phenotypic heterogeneity that impact their differentiation ability and hampers their safe application in clinical settings. Therefore, defining the molecular basis of phenotypic variability in pluripotent cells is a key challenge of developmental biology and modern biomedicine. We know that epigenetic regulation is crucial in the creation of cell-to-cell variability in pluripotent populations. However, we barely know the epigenetic regulators involved nor their mode of action. Combination of new genome-wide approaches and single-cell analysis will let us decipher how epigenetic factors regulate cell-cell variability and its impact in the differentiation potential of pluripotent cells.
  • 2. Epigenetic intratumor heterogeneity.
    At cancer diagnose tumours are composed of tens of millions of cells that have already diversified producing heterogeneous cell populations. Intratumoral heterogeneity (ITH) has been observed in solid tumours and its study is greatly 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 epigenetic heterogeneity is a key factor leading to functional cell-to-cell variability and different response to therapy. Additionally, genes encoding regulators of the epigenome are among the most commonly mutated genes in different cancer types. Thus, study of epigenetic regulators leading to epigenetic ITH will be key to design future effective treatments that minimize disease recurrence.

    Currently we are developing a set of projects to decipher how the activity of epigenetic factors (i.e. Polycomb proteins) are coordinated with mechanism that create cell-to-cell variability (i.e. cell cycle transition or circadian rhythms) to regulate pluripotency function and cancer progression. We aim to characterize novel regulatory mechanisms 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.

Funding

    • Universidad de Granada.
    • Consejería de salud de la Junta de Andalucía.
    • Consejería de economía, conocimiento, empresas y universidad de la Junta de Andalucía.
    • Asociación española contra el cáncer.
    • Ministerio de economía y competitividad.
    • Ministerio de educación, ciencia y universidades.
    • Laboratorio miembro de la red “International Nucleome Consortium”: Red Tematica MECU y COST European comisión.

Technology platforms

    • Omics analysis of DNA, RNA and proteins using state of the art equipment.
    • Single-cell analysis of DNA, RNA and proteins using state of the art platforms.

Additional information

More information: http://www.landeiralab.ugr.es

Selected publications

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