or
Continue with FacebookLooking to list your PhD opportunities? Log in here.
This project is no longer listed on FindAPhD.com and may not be available.
Click here to search FindAPhD.com for PhD studentship opportunities
Prof M Knowles
Applications accepted all year round
Competition Funded PhD Project (Students Worldwide)
About the Project
Accumulated knowledge of cancer genomics now provides insight into the mutational landscape of a wide range of human malignancies. Our studies of bladder cancer have identified genes with known or predicted involvement in disease pathogenesis. The challenge for the future is to understand how these genes contribute to tumour phenotype and particularly to therapeutic response and overall clinical outcome.
Human cell-based models can be used to test the function of candidate genes, examine the phenotypic consequences of specific molecular alterations and/or combinations of alterations and to test potential therapeutic strategies. We are using immortalised normal human urothelial cells to model bladder cancer pathogenesis and provide relevant preclinical models for drug development. This project will use somatic recombination technology (already established in our group) to develop isogenic cells with disease-relevant genotypes. This will include genes already known to play a role in tumour development and novel genes identified from our current exome sequencing analyses. Using both 2D and 3D culture methods, the consequences of these genomic alterations will be investigated using a range of phenotypic and molecular assays, including array-based methods.
Human cell-based models can be used to test the function of candidate genes, examine the phenotypic consequences of specific molecular alterations and/or combinations of alterations and to test potential therapeutic strategies. We are using immortalised normal human urothelial cells to model bladder cancer pathogenesis and provide relevant preclinical models for drug development. This project will use somatic recombination technology (already established in our group) to develop isogenic cells with disease-relevant genotypes. This will include genes already known to play a role in tumour development and novel genes identified from our current exome sequencing analyses. Using both 2D and 3D culture methods, the consequences of these genomic alterations will be investigated using a range of phenotypic and molecular assays, including array-based methods.
Funding Notes
Applications are welcome at any time, but deadlines exist for some awards. A number of competitive awards are available for both UK/EU and overseas students (http://scholarships.leeds.ac.uk/)
Self-funded students are welcome to apply but must be able to provide overseas rate University Tuition Fees (see UoL website) plus a minimum of £10,000 laboratory consumables costs per year. This is in addition to the provision of personal living expenses.
Applicants with sufficient funding must still undergo formal interview prior to acceptance in order to demonstrate scientific aptitude and English language capability.
Self-funded students are welcome to apply but must be able to provide overseas rate University Tuition Fees (see UoL website) plus a minimum of £10,000 laboratory consumables costs per year. This is in addition to the provision of personal living expenses.
Applicants with sufficient funding must still undergo formal interview prior to acceptance in order to demonstrate scientific aptitude and English language capability.
References
Chapman EJ, Hurst CD, Pitt E, Chambers P, Aveyard JS, Knowles MA (2006). Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway. Oncogene 25: 5037-5045.
Di Nicolantonio F, Arena S, Gallicchio M, Bardelli A (2010). Isogenic mutant human cells: a new tool for personalized cancer medicine. Cell Cycle 9: 20-21.
Gustin JP, Karakas B, Weiss MB, Abukhdeir AM, Lauring J, Garay JP et al (2009). Knockin of mutant PIK3CA activates multiple oncogenic pathways. Proc Natl Acad Sci USA 106: 2835-2840.
Knowles MA (2008). Bladder cancer subtypes defined by genomic alterations. Scand J Urol Nephrol Suppl: 116-130.
Di Nicolantonio F, Arena S, Gallicchio M, Bardelli A (2010). Isogenic mutant human cells: a new tool for personalized cancer medicine. Cell Cycle 9: 20-21.
Gustin JP, Karakas B, Weiss MB, Abukhdeir AM, Lauring J, Garay JP et al (2009). Knockin of mutant PIK3CA activates multiple oncogenic pathways. Proc Natl Acad Sci USA 106: 2835-2840.
Knowles MA (2008). Bladder cancer subtypes defined by genomic alterations. Scand J Urol Nephrol Suppl: 116-130.
Project supervisors
Career overview
Professor Margaret Anne Knowles is a leading figure in the field of Experimental Cancer Research at the University of Leeds, where she leads the Urothelial Cancers group within the Leeds Institute of Medical Research at St James''s. She obtained her first degree in Microbiology from the University of Bristol, followed by a PhD at the Imperial Cancer Research Fund (now known as Cancer Research UK London Research Institute), where her interest in epithelial cancer development was established. Following her doctoral studies, she undertook postdoctoral research at the Middlesex Hospital Medical School, focusing on human and rodent models for bladder cancer. Subsequently, she established her own research group at the Marie Curie Research Institute in Surrey, where she shifted her focus to the molecular features of human bladder cancer. Since 1997, she has continued her molecular studies of bladder cancer at Leeds, contributing significantly to the understanding of the disease and its treatment.
Research interests
Professor Knowles'' research focuses on the molecular features of urothelial carcinoma of the bladder, aiming to translate this information into clinical benefits. Their work employs a range of genomic and transcriptomic approaches to identify mutations, DNA copy number alterations, and expression changes that can enhance tumour classification at diagnosis, provide prognostic and/or predictive biomarkers, and suggest new therapeutic strategies. A significant current emphasis is on non-invasive bladder cancers. Professor Knowles utilises tumour cells and normal urothelial cells to investigate the function of key genes and is developing relevant preclinical models through the sequential manipulation of normal human urothelial cells.
Bladder Cancer Research
Genomics
Transcriptomics
Preclinical Models
Urothelial Carcinoma
Tumour Classification
Prognostic Biomarkers
Predictive Biomarkers
Non-Invasive Bladder Cancers
Molecular Features
Key Genes
Tumour Cells
Urothelial Cells
Cancer Therapy
Molecular Studies
Cancer Pathogenesis
Molecular Biology
Cancer Genetics
Oncogenic Mechanisms
Drug Delivery
Cancer Biomarkers.
