Dr Simon Baker

Research

Our lab is focused on an epithelial tissue, known as “urothelium”, that lines the urinary tract; from the renal pelvis in the kidneys, down the ureters and into the bladder. We work primarily with laboratory human tissue models. Much of our work involves cutting-edge genomic and transcriptomic methods, which are used to examine how the genes of cells can be damaged and the ways in which the genes are used in response. A particular recent focus has been the diagnostic patterns of DNA-damage left in the genome by specific events, known as “mutational signatures”. A mutational signature can be used, much like a fingerprint, to identify the causes of DNA damage and establish the relevant risk factors for different cancers.

What causes bladder cancer?

The main focus of our research seeks to address this simple question. Because this question remains incompletely answered, there has been little progress in the prevention of bladder cancer.

The urothelium spends your whole life exposed to concentrated toxins in the urine. Some of these toxins damage the DNA and we are looking at whether certain chemicals leave their signature in the DNA, in the form of specific mutation types. These mutational signatures might help explain the cause of the cancer in each individual and potentially guide treatment approaches.

We were the first to describe a method for deriving mutational signatures from a carcinogenic exposure in an in vitro differentiated human tissue model (published in European Urology).

Could a virus be the cause of bladder cancer?

The vast majority of mutations we find in bladder tumours don’t carry the signature of chemical carcinogens. In bladder cancers the predominant mutational signatures originate from cytidine deamination by antiviral enzymes known as “APOBECs”.

Most bladder cancer genomes harbour a mixture of the single base substitution signatures SBS2 and SBS13, which have been ascribed to APOBEC-mediated cytosine deamination. APOBECs are better known for their role in damaging viral genomes and particularly those with DNA-based genomes.

Implicating BK virus

My Kidney Research UK fellowship is looking at BK virus, which is a common childhood viral infection. BK virus is known to establish a persistent infection of the kidney that survives into adulthood and can become reactivated during periods of immune limitation. When BK virus becomes reactivated it can be detected in the urine. Our work has shown that BK infection of the urothelium leads to the activation of APOBECs which damage the genome (published in Oncogene).

More recently, we have shown the APOBEC damage induced by BK virus infections leads to the formation of mutational signatures (SBS2 and SBS13) in our models of the normal human urothelium and comparisons with tumour genomes show striking similarities (published in Science Advances).

Is bladder cancer preventable?

Our research on BK virus is growing and, alongside our traditional in vitro mechanistic work, we are now running epidemiological studies and research looking at novel therapeutic approaches. Our aim is to establish whether bladder cancer could be a preventable disease if timely antiviral interventions were available.

Helping those suffering from BK virus infections

With our aim to improve the lives of those suffering from BK infection, our public and patient involvement (PPI) work helps develop the research. Working with patients like Tim Tavender is critical to ensure the research remains focussed and that the data drives evidence-based change in clinical practice to improve the lives of patients.

We use our research to drive improvements in the patient experience whenever we can. Examples include contributing to the first UK clinical guideline on managing BK virus infections, developing evidence based patient information and pushing for improvements in BK virus testing/screening through the UKKA rare disease group. 

Opportunities to work with us

PhD Studentships

• External scholarship or self-funded students can always get in touch to see if there are openings.

Masters by Research Studentships

• 1 year programmes - please send a CV and short email of interest to simon.baker@york.ac.uk 

Patients

If you are interested in our research programme, please reach out to us and we will be happy to discuss opportunities for getting involved.

Teaching

Through my involvement with York Against Cancer, I am leading an Enthuse partnership with local schools seeking to improve cancer teaching quality and its integration throughout the secondary curriculum.

In the University I supervise undergraduate, masters and doctoral research students in their laboratory research and run tutorials.