Paediatric Solid Tumour Biology and Therapeutics Group

Professor Louis Chesler’s group is investigating the genetic causes for the childhood cancers, neuroblastoma, medulloblastoma and rhabdomyosarcoma. 

Research, projects and publications in this group

Our group's aim is to improve the treatment and survival of children with neuroblastoma, medulloblastoma and rhabdomyosarcoma.

The goal of our laboratory is to improve the treatment and survival of children with neuroblastoma, medulloblastoma and rhabdomyosarcoma, three paediatric solid tumours in which high-risk patient cohorts can be defined by alterations in a single oncogene. We focus on the role of the MYCN oncogene, since aberrant expression of MYCNis very significantly associated with high-risk in all three diseases and implies that they may have a common cell-of-origin.

Elucidating the molecular signalling pathways that control expression of the MYCN oncoprotein and targeting these pathways with novel therapeutics is a major goal of the laboratory. We use a variety of innovative preclinical drug development platforms for this purpose.

Technologically, we focus on genetically engineered cancer models incorporating novel imaging (optical and fluorescent) modalities that can be used as markers to monitor disease progression and therapeutic response.

Our group has several key objectives:

  • Mechanistically dissect the role of the MYCN oncogene, and other key oncogenic driver genes in poor-outcome paediatric solid tumours (neuroblastoma, medulloblastoma, rhabdomyosarcoma).
  • Develop novel therapeutics targeting MYCN oncoproteins and other key oncogenic drivers
  • Develop improved genetic cancer models dually useful for studies of oncogenesis and preclinical development of novel therapeutics.
  • Use such models to develop and functionally validate optical imaging modalities useful as surrogate markers of tumour progression in paediatric cancer.

Professor Louis Chesler

Clinical Senior Lecturer/Group Leader:

Paediatric Solid Tumour Biology and Therapeutics Professor Louis Chesler (Profile pic)

Professor Louis Chesler is working to understand the biology of children’s cancers and use that information to discover and develop new personalised approaches to cancer treatment. His work focuses on improving the understanding of the role of the MYCN oncogene.

Researchers in this group

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Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6124

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OrcID: 0000-0003-3977-7020

Phone: +44 20 3437 6109

Email: [email protected]

Location: Sutton

I obtained an MSci in Biochemistry from the University of Glasgow in 2018. In October 2018 I joined the labs of Dr Michael Hubank and Professor Andrea Sottoriva to investigate the use of liquid biopsy to monitor clonal frequency and emergence of resistance mutations in paediatric cancers.

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Email: [email protected]

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Professor Louis Chesler's group have written 112 publications

Most recent new publication 1/2025

See all their publications

Vacancies in this group

Working in this group

Head of Biology and Director, Centre for Target Validation (Group Leader)

  • Sutton
  • Cancer Therapeutics
  • Competitive Starting Salary
  • Permanent

Under the leadership of Dr Olivia Rossanese, we are seeking to appoint a Team Leader to join The Centre for Cancer Drug Discovery (CCDD) as The Head of Biology and Director of the Centre for Target Validation. Key Requirements The successful candidate must have in-depth knowledge and recent experience in an area of cancer biology relevant to oncology drug discovery. Leadership experience of drug discovery within, or in collaboration with, the pharmaceutical or biotechnology industry as evidenced by publication and/or successful commercial projects. Along with completing the online application form, you will be asked to attach the following documents and failure to do so will mean your application cannot be considered on this occasion: · Full CV · Lists of major publications, achievements, research grants, distinctions. · A PDF of a maximum of five key publications, or other research outputs (e.g. patents) that best demonstrate previous productivity · You must also complete the personal statement section of the application form in the format of a covering letter including the names and contact details of three academic referees Department/Directorate Information: The Division of Cancer Therapeutic's mission is to develop personalised medicines by translating information from the cancer genome and cancer biology into drugs for patient benefit. We implement innovative drug discovery technologies, discover novel mechanism-based drugs, and develop these as rapidly as possible from the laboratory through to hypothesis-testing early clinical trials We encourage all applicants to access the job pack attached for more detailed information regarding this role. For an informal discussion regarding the role, please contact Dr Olivia Rossanese, Email [email protected]

Postdoctoral Training Fellow - Mechanisms and Regulation of pre-mRNA Splicing

  • Chelsea
  • Mechanisms and regulation of pre-mRNA splicing
  • Salary Range: £35,844 - £45,600 per annum
  • Fixed term

Under the leadership of Professor Vlad Pena, we are seeking to appoint a Postdoctoral Training Fellow with a strong interest in the structural biology of RNA-protein complexes. The primary objective of this project is to elucidate how RNA splicing is regulated by a specific set of chromatin factors. The successful candidate will focus on reconstituting spliceosomes involved in this process and determining their structures using cryo-electron microscopy (cryo-EM). Comprehensive training in specialized techniques will be provided. Our laboratory offers regular access to cutting-edge structural biology facilities, including recombinant protein expression, purification systems, mammalian cell bioreactors, advanced electron microscopy (Glacios and Titan Krios), high-performance GPU computing clusters, mass spectrometry, and both preparative and analytical biochemistry tools. More detailed information about our research can be found on our webpage. For general information on Post Doc's at The ICR can be found here. Key Requirements The successful candidate must have a PhD (or equivalent) in structural biology and demonstrate strong expertise in the biochemistry of macromolecular complexes. While experience in RNA biology, the structural study of RNA-protein complexes, and cryo-EM is advantageous, we encourage applications from all talented scientists with a passion for this field. The ICR has a workforce agreement stating that Postdoctoral Training Fellows can only be employed for up to 7 years as PDTF at the ICR, providing total postdoctoral experience (including previous employment at this level elsewhere) does not exceed 10 years Department/Directorate Information: The Division of Structural Biology is located at the ICR site in the picturesque Chelsea district of London, offering a vibrant scientific and cultural atmosphere and excellent opportunities for both personal and professional growth. We encourage all applicants to access the job pack attached for more detailed information regarding this role. For an informal discussion regarding the role, please contact Prof Vlad Pena at [email protected]

Industrial partnership opportunities with this group

Opportunity: A novel test for predicting future cancer risk in patients with inflammatory bowel disease

Commissioner: Professor Trevor Graham

Recent discoveries from this group

30/01/25

Scientists at The Institute of Cancer Research, London, have found a way to identify people with inflammatory bowel disease (IBD) who are at the highest risk of developing bowel cancer.

IBD includes ulcerative colitis and Crohn’s disease. They irritate the lining of the bowel, which can cause abnormal pre-cancerous cells to form if left untreated. Having these conditions can increase your risk of bowel cancer, especially if you have had them for several years. According to the charity Crohn’s and Colitis UK, one in 123 (around 500,000 people) in the UK have Crohn’s disease or ulcerative colitis.

Identifying the people more likely to develop bowel cancer

In a study published today in the journal Gut, scientists at The Institute of Cancer Research (ICR), funded by Cancer Research UK and the Barts Charity and working with doctors at St Mark’s Hospital, the UK’s specialist bowel hospital, revealed that people with IBD whose pre-cancerous cells had lost or gained multiple copies of their DNA were far more likely to go on to develop bowel cancer. The scientists created an algorithm that calculates the risk of future bowel cancer, based on the exact pattern of the DNA altered in the pre-cancerous cells.

The scientists found that this method can predict which people with IBD who develop pre-cancerous cells will go on to develop bowel cancer within 5 years with greater than 90% accuracy. This method could be used in hospitals to test for bowel cancer risk in people with IBD in the coming years.  

Sparing those who are not at high risk from tough decisions

Professor Trevor Graham, Professor of Genomics and Evolution and Director of the Centre for Evolution and Cancer at The Institute of Cancer Research, London, said:

“Most people with ulcerative colitis or Crohn’s disease won’t develop bowel cancer. But for those that have these conditions and are showing signs of pre-cancer in their colon, there are some tough decisions to make. Either they have it monitored regularly, in the hope that it doesn’t become cancer, or they have their bowel removed to guarantee they don’t get cancer in the future. Neither of these options are particularly pleasant.

“Crohn’s and ulcerative colitis are common and we need better tools to identify the patients at highest risk of bowel cancer. Our test and algorithm give people with IBD, and the doctors who care for them, the best possible information so that they can make the right decision about how to manage their cancer risk. We can accurately identify those people at high risk whilst putting the minds of many others at rest.”

Algorithm calculates risk

The test would use genomic sequencing to check the number of copies of DNA from samples of pre-cancerous growths taken from the lining of the gut during endoscopy. Information from the sequencing would be fed into an algorithm, which calculates their risk based on which copies of DNA are altered, alongside other information such as the size of the growth, how easy it was to remove during biopsy and how inflamed the gut is overall.

Currently, people with IBD are offered regular checks for pre-cancerous growths in the lining of the gut. People with the pre-cancerous growths (known as low grade dysplasia or LGD) have around a 30% chance of bowel cancer developing over 10 years. If the patient has LGD, they are classed as high risk and offered treatment to prevent the pre-cancerous cells developing into bowel cancer.

The treatments are bowel removal surgery, which has life-changing side effects such as carrying a stoma bag, or regular monitoring with colonoscopies, which are invasive, time-consuming and cause worry and anxiety for patients because they live with the fear that they may develop bowel cancer in the future.

Craig Foster, from Waterlooville, lost his wife Fariba to bowel cancer in February 2024.

Craig and Fariba Foster. Craig is on the let in a blue suit, Fariba is on the right in a patterned shirt. They are both smiling.

Fariba, who worked as a dental receptionist, had lived with ulcerative colitis since she was 18, when she had three-quarters of her bowel removed. Craig said:

“Cancer takes no prisoners and it doesn’t matter who you are or from what walk of life, everyone is affected in some way. Fariba died just six months after she was diagnosed. Even though it was a short time, it was the worst time.

“Research like this will save lives. It gives me comfort to know that there are scientists working right now so that no-one has to experience the same situation Fariba was in.”

The only way to find these pre-cancerous cells is through biopsy, but it does not reliably tell doctors which pre-cancers will eventually become bowel cancer. Scientists hope that the test could spare those who are at much lower risk from the stress of regular colonoscopies or the life-changing impact of surgery to remove the colon.

In the study, samples of pre-cancerous cells were taken from 122 patients with IBD. Around half of the patients subsequently went on to develop bowel cancer 5 years after the sample was taken, whilst the other half remained cancer-free after 5 years. All of the samples had their full DNA scanned to look for changes in the structure and number of copies in the DNA. The scientists found that patients with IBD who developed bowel cancer had lost multiple copies of their DNA.

In future studies, the scientists are hoping to develop the test beyond analysing samples of growths taken from the gut to a less invasive method, such as taking a blood sample.

‘Finding smarter ways to assess these colons is much needed’

Professor Ailsa Hart, Lead of the inflammatory bowel disease research unit at St Mark’s the National Bowel Hospital and co-lead of the study, said:

"Patients with inflammatory bowel disease have a higher risk of developing colorectal cancer than people without IBD, and need to undergo assessment with regular colonoscopies to try to detect early signs of cancer. These tests are onerous and unpleasant for patients, imperfect at detecting early cancer changes and costly to health services.

“If early signs of cancer are detected, surgery, which involves removing the colon, is advocated. Finding smarter ways to assess these colons is much needed.

“Here we describe a potential biomarker, which can be readily translated into clinical practice, to improve assessment of patients with IBD and early signs of cancer to help with the decision for surgery.”

‘Until now we have had to take a one-size-fits-all approach’

Dr Ian Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said:

“Treatment for bowel cancer is far more likely to be effective if you catch the disease earlier. Having Crohn’s or colitis is a known risk for bowel cancer but the risk varies widely between different people, and until now we have had to take a one-size-fits-all approach to preventing it.  

“Genome sequencing is now far cheaper and more widespread than ever before, and it’s changing how we look at cancer. Getting a full readout of tumour DNA means we can see a much bigger picture of how someone’s cancer started and how it is likely to change over time.

“With this research, we can focus resources on treating people with IBD who are at really high risk, saving health services valuable time and money. We can also give those at lower risk peace of mind and remove the fear of bowel cancer in the future.”