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Wellcome-MRC Cambridge Stem Cell Institute

 

 

Professor Anna Philpott

 

Proneural transcription factors

Email: 

Laboratory: Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre

Departmental Affiliation: Department of Oncology

 

Biography

Anna Philpott graduated from the University of Cambridge with a BA degree in Natural Sciences in 1988 and a PhD in Molecular Cell Biology in 1991.  She held post-doctoral fellowships at Massachusetts General Hospital Cancer Centre in 1992, moving to the Department of Cell Biology at Harvard Medical School in 1993. 

She returned to the University of Cambridge in 1998 to a Lectureship in the Department of Oncology, where she is currently Professor of Cancer and Developmental Biology and Head of the School of the Biological Sciences.

 

Funding

Cancer Research UK, Wellcome Trust

 

(A) Neurons generated by transcription factor-mediated forward programming. (B) Neurons stained purple in a developing Xenopus frog embryo. (C) Confetti coloured labelling of pancreatic ducts.

 

Research

We aim to characterise mechanisms that control the ability of cells to respond to cell fate challenges, as well as explore mechanisms that co-ordinate cell cycling with stem cell maintenance and differentiation during development, homeostasis and disease.  In particular, we have uncovered a conserved regulatory mechanism where cdk-dependent phosphorylation of multiple proneural proteins promotes maintenance of progenitor/stem status, while dephosphorylation drives differentiation. 

Our future aims are three-fold: we will explore how distinct fate-specifying transcription factors induce different responses at different developmental stages at the embryo, tissue and single cell level; we will further characterise the molecular mechanisms that link cell cycling and differentiation: We will also investigate perturbation of the balance between stem-ness/progenitor maintenance and differentiation that is a frequent hallmark of multiple cancers, focusing on molecular regulation of proliferation and differentiation in neuroblastoma, with the aim of developing new therapeutic strategies.

 Philpott group 2020

Group Members

Frances Connor, Lidiya Mykhaylechko, Toshiaki Shigeoka, Lydia Parkinson, Laura Woods, William Beckman, Roberta, Azzarelli, Rosalind Drummond

 

Plain English

Controlling the balance between division of cells and the process of differentiation, whereby cells stop dividing and adopt their specialised function, is critical both in development and in adult tissues that must maintain and repair themselves. Moreover, in many cancers and in particular cancers of children, this balance is disrupted. We are investigating the role of a class of proteins, the proneural factors, in controlling the fate choices cells make as well as their cell division and differentiation, and how their activity is controlled by chemical modification in response to their cellular environment. We are: - Studying how chemical modification of proneural proteins controls cell division versus differentiation in the nervous system, pancreas and gut. - Investigating how proneural proteins work to turn on different genes to either change their fate, promote cell division or arrest it, depending on the environment the cells are in. - Developing treatments for the childhood cancer neuroblastoma by changing the chemical modification of proneural proteins using new drugs. In the longer term, our understanding of the control of this crucial class of proteins, the proneurals, will help us to turn stem cells into useful tissues such as nerve and pancreas, as well as aid us in rational development of new therapies for cancers where proneural protein activity has been disrupted.

 

Key Publications

The Philpott Group

Philpott Group members: 

Will Beckman
Frances Connor
Rosalind Drummond
Kirsty Ferguson
Fiona Grealy
Samina Kauser
David Lando
Jethro Lundie-Brown

Lidiya Mykhaylechko