KKLF Intermediate Fellow
Research themes:Stem Cell, Cancer, Haematopoiesis, normal and malignant
Description of research
Haematopoietic stem cells balance molecular programmes of self-renewal and differentiation in order to sustain mature blood cell production and maintain a pool of undifferentiated multipotent cells throughout the lifetime of the individuals. Corruption of some of these programmes in favour of self-renewal and/or blocking differentiation may result in malignant transformation to generate leukaemia. Additionally, stem cells have the capacity to respond to increased demands in production of mature lineages, e.g. upon injury.
In unicellular organisms such as bacteria and yeast, variability in gene expression has been shown to influence cell fate and population evolution in response to changing environmental conditions. My previous observations of increased cell-to-cell transcriptional variability in early lineage decisions (Pina et al, 2012; Teles et al 2013) suggest that similar mechanisms may operate in mammalian stem cell systems.
The aims of our group are to understand the role and regulation of transcriptional heterogeneity in normal and malignant cell fate decisions, and to mechanistically explore candidate modulatory pathways as therapeutic targets in haematological malignancy. For that, we use a combination of functional and molecular studies of mouse models and cultured and primary human cells, where individual genes and pathways have been perturbed, with a particular focus on single-cell transcriptional analysis.
We benefit from a strong interdisciplinary network of collaborators, both local to Cambridge and externally, and state-of-the-art facilities for molecular, mechanistic and functional studies.
We are always keen to hear from enthusiastic and talented people, so do email me (firstname.lastname@example.org) if you are interested in joining our research efforts.
Kay Kendall Leukaemia Fund Intermediate Fellowship
Isaac Newton Trust Research Grant
Rosetrees Trust PhD studentship (for Liliana Arede)
Keywords: Haematopoietic stem cells; Cell fate decisions; Leukaemogenesis; Transcriptional noise
Clinical conditions: Leukaemia; Acute Myeloid Leukaemia
Methodologies: Functional assays in vivo and in vitro; Single-cell transcriptional profiling; Mouse models; Primary human cells; Lentiviral transduction; Flow cytometry; Genome-wide profiling (RNA-Seq and ChIP-Seq); Proteomics