Professor Julia Newton-Bishop

Profile

I trained in general medicine on the London Hospital Medical Rotation and then in dermatology in London, at St Thomas's Hospital and the St Johns Institute of Dermatology. I completed my thesis in the Richard Dimbleby Department of Cancer Research and was then appointed as Senior Lecturer (Honorary Consultant) at the Royal London Hospital in 1989. In the following 6 years I carried out a case-control study of melanoma which described phenotypes associated with melanoma risk, and we started to recruit families with multiple cases of melanoma, to a programme of research designed to understand the causes of familial melanoma.

In 1995 I moved to Leeds. Since then I have worked with Professor Tim Bishop and a group of experienced technicians and statisticians and the group is now formally part of the Immunology subgroup of the Institute of Medical Research at St James's. The research funding has been primarily from ICRF and then Cancer Research UK, as consecutive programme grants. We have benefitted however from three consecutive collaborative NIH R01s, a MRC project grant, a large Network of Excellence grant from the EU under Framework 6, and smaller grants from charities such as Melanoma Focus, the Skin Diseases Research Fund and the AICR. In 2000 we broadened the research aims to ask what inherited, somatic tumour events and exposures moderate melanoma survival. We have built very large cohorts in order to address these aims.

I played a key role in establishing UK and European Clinical Guidelines, and have been involved in other UK committees designed to inform management. 2004-2005 I was a member of the NICE Skin Cancer Guideline Committee, 2012-2015 I was the clinical chair for the NICE Melanoma Clinical Guideline. I was chairman of the NCIN Skin Cancer Committee from 2009-2014 during which we defined the COSD data sets.

In 1997 I instigated and have since then been chairman of the international melanoma genetics consortium GenoMEL. This consortium has led the way internationally in the identification of common and rare inherited genetic variants associated with melanoma risk. This is important in terms of understanding the biology of melanoma aetiology, giving insight into prevention, and for the rare high penetrance genes the long-term aim is to understand risk and to instruct proper screening programmes.

We are now, in 2022 working with the University of Oxford to build a cohort of at least 20,000 participants who have had melanoma treated by the NHS, in order to build a data resource to be used by international researchers to address the key remaining issues for the prevention and management of melanoma. Particular attention will be paid to the identification of biomarkers and improving the understanding or and management of drug toxicities and the effects of melanoma and its treatment on the quality oflife of affected patients. The project is called MyMelanoma and we hope to start recruiting January 1^st 2023.

Responsibilities

• Lead Melanoma Research Group
• Leeds Institute of Medical Research at St James’s

Research interests

I lead a research group in the Institute of Medical Research at St James's which is part of the University of Leeds. The research group uses epidemiology and genomics (of the germline and tumour) to understanding susceptibility to melanoma and survival from melanoma.

We have published extensively on high-risk susceptibility genes and more recently on large genome wide association studies designed to identify low to medium penetrance susceptibility genes. I have been Chairman of the international melanoma genetics consortium GenoMEL since 1997. Under my leadership the consortium has successfully obtained funding from the NIH and from the EU under FP6. The EU grant was for 10.5 million euros. This research has produced 4 Nature Genetics papers in the last 3 years.

Just as susceptibility to cancer is governed by heredity, and the environment, our hypothesis is that the probability of survival for cancer patients is also modified by heredity and the environment as well as variation in the biological characteristics of the tumours themselves. Current research in Leeds is directed toward understanding these modifiers. I have set up a second consortium called BioGenoMEL, and this consortium was created in order to pool data from research groups internationally to generate enough statistical power to identify inherited genetic variation having an effect on melanoma survival. By finding genetic variation which modifies survival expectation, we will identify important biological processes governing host/tumour interaction which may promote the recognition of novel therapies for cancer.

The focus of the research in recent years has shifted to include the aim of understanding environmental factors which modify that interaction between the patient and his/her tumour. In order to do that we have built very large cohort studies: collecting complex data sets on lifestyles, blood samples and tumour samples from melanoma patients. We are grateful to those patients for their time and willingness to donate their samples. The largest study is known as the Leeds Melanoma Cohort in which 2184 patients participated see plain English summary below https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-why-melanoma-skin-cancer-comes-back-after-surgery

We have reported evidence that smoking reduces survival in melanoma patients and that this is most marked in patients whose tumours contain a stronger immune reaction: something that usually increases the expectation of survival (Pozniak et al Cancer Research 2019). We first reported evidence that higher vitamin D levels at melanoma diagnosis was associated with thinner tumours and better survival in 2009. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19770375.

These findings have since been recapitulated in other studies from the USA, Germany and Australia. We continue to work on studies designed to understand the biological processes associated with the association between vitamin D and better melanoma survival.

In 2022 we continue to use genomic data to understand the biological processes underlying tumour progression and the immune responses to melanoma. Paraffin embedded tissue and blood samples have been used to generate unique transcriptomic data allowing bioinformatic interrogation of the nodal genes and signalling pathways.

Grants

Current funding

Title: Genetic Epidemiology of Melanoma

Ref: RO1 CA083115

Dates: 1st January 2014 – 31st March 2019

Co-PI: DTB

Funder: National Institute of Health

Award: $520,000 to University of Leeds

Title: Metformin and survival from melanoma

Dates: 1st February 2015 – 31st January 2019 (extended)

PI: JNB

Funder: Melanoma Focus

Award: £8.7k

Title: Genetic Epidemiology of Melanoma

Ref: RO1 CA083115

Dates: 1st January 2014 – 31st March 2019

Co-PI: DTB

Funder: National Institute of Health

Award: $520,000 to University of Leeds

Title: Using tumour, peripheral blood and sentinel nodal transcriptomics to understand the interaction between melanomas and the host

Ref: MR/M019012/1

Dates: 1st June 2015 – 31st May 2020

PI: JNB

Funder: Medical Research Council

Award: £953,389

Title: MELGEN – Understanding and biomarking the genetic and immunological

determinants of melanoma survival – Marie Curie ETN Training Network

Ref: 641458

Dates: 1st June 2016 – 31st May 2019

PI: JNB

Funder: European Union

Award: £4.0m

Title: The role of genetic susceptibility in melanoma development

Ref: RO1 CA182890-01

Dates: 1st May 2014 – 30th April 2019

Leeds PI: JNB

Funder: National Institute of Health

Award: $280k to Leeds

Title: Genetics of acral melanoma: Newton Senior Fellowship for Dr Daniela Robles

Espinoza (Mexico-UK Award)

Dates: 1st December 2018 - 30th November 2023

PI: Daniela Robles Espinoza (Mexico), DTB Co-PI

Funder: Academy of Medical Sciences

Award: £100k

Qualifications

• MB ChB
• MD

Professional memberships

• FMedSci

Student education

Teaching: post graduate education

Genetics, somatic, germline, melanoma survival, melanoma aetiology, vitamin D

Postgraduate Students

Students since 2013 listed

Anastasia Filia PhD 2009-2013

Sinead Field 2010-2014 MD student

Sally O’Shea PhD 2013-2017

Faheem Latheef MD student 2019

Rohit Thakur PhD 2015-19

Joanna Pozniak PhD 2015-19

Sathya Muralidhar PhD 2015-19

Joey Diaz PhD 2016-19

Emily Clarke – current PhD student

Scott Gregory – current PhD student

Fiona James – current PhD student

Research groups and institutes

• Leeds Institute of Medical Research at St James's