ISTM

Summary of career history:

• 2009 onwards: Lecturer in Bioscience, Keele University School of Medicine / Institute for Science and Technology in Medicine (UK) Nucleoli, ribosome biogenesis and cancer
• 2006 – 2009: Post-doctoral researcher, School of Life Sciences, Södertörn University / Department of Biosciences and Nutrition, Karolinska Institutet (Sweden) c-Myc, nucleoli and cancer, supervised by Prof Anthony Wright
• 2001 – 2005: PhD in Molecular Oncology, University of Dundee (UK) Discovering novel, non-genotoxic activators of p53, supervised by Prof Sir David Lane and Dr Sonia Laín.
• 2001 Mbioch, University of Oxford (UK)

As a PhD student, I established cell-based assays to screen for novel small molecule activators of p53, and this was later scaled up into a high-throughput system which has identified several compounds now in clinical trials. While investigating hits from the primary screen, I became interested in activation of p53 via inhibition of ribosomal DNA transcription and disruption of nucleolar integrity.

This led me to a post-doc on the role of the oncogenic transcription factor c-Myc in direct activation of ribosomal DNA transcription. The rate of ribosome production determines a cell's capacity for protein synthesis, increase in cell size and ultimately cell proliferation. This pathway is important not only in cancer but also in other pathologies such as cardiac hypertrophy. Changes in nucleolar chromatin, which occur very rapidly when cells are stimulated to grow, may be useful for assessing the efficacy of drugs which aim to block c-Myc's oncogenic effect.

My current research combines these two elements to look at the roles of nucleoli and ribosome biogenesis pathways in normal cell growth and in cancer. I am considering the ways that normal or pathlogical growth signals, can impinge on nucleolar function. I also aim to understand how cells can sense and respond to stresses that disrupt ribosome biogenesis, and how these protective mechanisms may fail in a cancer situation.

ISTM Research theme: 1. Clinical & Diagnostic Science

Research Interests:

• Ribosome biogenesis and its impact on cell growth and cancer
• Signalling nucleolar disruption and nucleolar stress
• Non-traditional roles of the ubiquiitin-proteasome system
• Cell-based assays for selection and quality assessment of potential cancer drugs

My main research focus is the regulation of cell growth by tumour suppressors and oncogenes. Understanding these pathways is important for identifying and validating drug targets, with the aim of developing tailored cancer treatments. They can also shed light on basic biological questions around the evolutionary development of multicellularity.

I have broad experience working with the tumour suppressor p53, which ismutated or deleted in the majority of human cancers, and with the oncogenec-Myc, implicated in approximately 1 in 7 deaths in the developed world. I currently work with Gwyn Williams and PhD student Leanne Patrick to characterize a novel cell fate regulator with both pro-apoptotic and pro-proliferation activity.

I teach elements of the undergraduate curriculum for the Keele University MBChB in the School of Medicine.

Currently, I am Unit Lead for Year 2, Unit 1 "Inputs and Outputs". I am a PBL tutor for Years 1 and 2, and deliver lectures on cell biology of cancer. With Simon Gay I co-lead the Academic Advisors programme. I am also link tutor for the Health Foundation (Medicine) course.