Topham, Caroline - University of Salford - Biomedical Research Centre

个人简介

I joined the University of Salford as a Lecturer in October 2015, motivated by a desire to combine my passion for teaching with my track record of high quality research. Prior to this, I spent over 4 years performing my Post-Doctoral research at the University of Manchester, based in Professor Stephen Taylor’s lab. Here we were interested in identifying ways of sensitizing tumour cells to anti-mitotic drugs, a class of chemotherapeutic commonly used in clinics around the world. Using a genome-wide screening approach we were able to identify the mechanism of the oncogene c-Myc in the regulation of death in response to the anti-mitotic Taxol, an observation we published in Cancer Cell in 2015. Before this, I completed my PhD in Cell Biology at the University of Manchester in 2010, supervised by Professor Richard Walmsley and based in the labs of Gentronix, a University biotechnology spin-out company. This industrial setting exposed me to technologies such as high-throughput cell-based reporter assays. My research here was concerned with the interplay between apoptotic and DNA damage networks, and was partially funded by GSK, allowing me to work with this industrial partner in order to learn toxicological assays, and experience the industrial approach to research. I then worked as a Research Scientist with Gentronix for a year, to expand on and publish the observations I had made during my PhD. My research career first started in 2003 whilst working, initially as a Technician and then as a Research and Development Scientist, for the contract research organisation Cyprotex. My work here was concerned with characterising the pharmacokinetic properties of novel pharmaceuticals, including an assessment of their predicted safety in humans using cell-based assays.

研究领域

I am a cancer cell biologist with a specific interest in identifying ways of improving patient outcomes in response to existing chemotherapies. My most recent research identified the oncogene Myc as a key regulator of death in response to the widely used anti-cancer drug Paclitaxel, which is commonly used to treat cancers of the breast, ovary and lung, amongst others. This study has important ramifications for how we treat cancer patients with this drug in the future, and also identified a strategy for sensitizing tumour cells to Paclitaxel using a combination therapy, an observation we hope will translate into the clinic. Current research applies my experience of the complex nature of Myc signaling to the problem of poor patient outcomes for children with brain cancers, both in terms of survival rates and late-onset side effects. Medulloblastoma, in particular, is particularly aggressive when Myc is expressed at high levels and, in collaboration with Dr Gianpiero Di Leva, we aim to understand how Myc signaling achieves this, with particular focus on key microRNA networks. We hope that a clearer picture of the role Myc targets have in the progression of this disease will allow us to design new ways of enhancing current treatment regimes. My interest in childhood cancers also extends to leukaemia, which poses a very different problem to medulloblastoma, in that survival rates are actually very good at over 80%, but the problem of late effects in cancer survivors is increasing. It is not uncommon for childhood cancer survivors to suffer from a range of chronic disorders as a result of their treatment, including obesity. To further complicate matters, obese patients are more likely to relapse after treatment for leukaemia. In collaboration with Dr Sarah Withers, we aim to understand the molecular crosstalk between adipose tissue and leukaemia cells, with a view to improving outcomes for obese patients, and potentially identifying ways in which acquired obesity during treatment can be reduced. I also have a long-standing interest and expertise in screening technologies and high throughput techniques, including high content automated microscopy, which stems from my industrial background. Currently I am collaborating with an industrial partner, based at the BioHub in Alderley Park, to explore the toxicity of novel compounds destined for use in antibody drug conjugates. My continued interest in collaborating with industrial partners over the years stems from a desire to perform relevant research, with real-world applications.

近期论文

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Sloss, O., Topham, C.H., Taylor, S.S. (2016) Mcl1 dynamics influence mitotic slippage and death in mitosis. Oncotarget. doi: 10.18632/oncotarget.6894. [Epub ahead of print] Topham, C.H., Tighe, A., Ly, P., Bennett, A., Sloss, O., Nelson, L., Ridgway, R.A., Huels, D., Littler, S., Schandl, C., Sun, Y., Bechi, B., Procter, D.J., Sansom, O.J., Cleveland, D.W., Taylor, S.S. (2015) MYC is a major determinant of mitotic cell fate. Cancer Cell. 28(1) 129-40. Topham, C.H., Taylor, S.S. (2013) Mitosis and apoptosis: how is the balance set? Current Opinion in Cell Biology, 25(6), 780-5. Topham, C.H., Billinton, N., Walmsley, R.M. (2012) Nongenotoxic Apoptosis Inducers Do Not Produce Misleading Positive Results in the TK6 Cell-Based GADD45a-GFP Genotoxicity Assay. Toxicological Sciences, 128(1), 79-91.