Email: nancy.papalopulu@manchester.ac.uk

Research profile and key clinical specialties

During development, cells transition from a proliferating progenitor to a differentiated state or to a dormant one (quiescence) from which they may be reactivated. Understanding how such cell state transitions are regulated is key in understanding how tissues are built in development, maintained in the adult, repaired or subverted to disease, particularly cancer.

My lab’s working hypothesis is that cell state transitions are not simply driven by genes being turned on (or off) as cells make transitions, but by a change in the dynamics of gene expression, for example, from fluctuating or oscillatory (pulsatile) expression to a more stable one.

We use state of the art single cell approaches, with absolute quantitation of interacting molecules, live imaging, multiple experimental model systems (neural stem cells from mouse, human, zebrafish) and mathematical modeling, in order to understand how changes in gene expression dynamics underlie cell state transitions.

We focus on vertebrate neurogenesis and we aim to apply the emerging concepts, particularly the entry to and exit from quiescence, to cancer and regeneration.

Two key publications

• Phillips, N., Manning, C., Pettini, T., Biga, V., Marinopoulou, E, Stanley, P, Boyd, J., Bagnall, J., Paszek, P., Spiller, D., White, M., Goodfellow, M, Galla, T, Rattray. M, Papalopulu, N. (2016) Stochasticity in the microRNA/Hes1 oscillatory network accounts for clonal heterogeneity in the timing of differentiation, eLIFE, in press.
• Sabherwal, N., Thuret, R., Lea R., and Papalopulu, N. (2014). Phosphorylation of a cell cycle inhibitor, p27Xic1, by a polarity kinase, aPKC, provides a direct mechanistic link between apicobasal polarization and control of the cell cycle, Dev Cell, 8(5): 559-71

Possible PhD projects

• Understanding how the dynamics of gene expression actively maintain quiescence in cancer stem cells.

More information

I am committed to developing young people’s careers and most PhD students graduated from my lab have 1st author publications.

Keywords: progenitor, quiescence, tissues, cancer, genes, vertebrate, neurogenesis, regeneration, clonal, heterogeneity, kinase, apicobasal, Nancy, Papalopulu, Manchester

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