Faculty of Medical Sciences

Staff Profile

Dr Neil Rajan

Wellcome Intermediate Clinical Fellow, Senior Lecturer and Honorary Consultant Dermatologist

Background

 

Dermatogenetics group

Our major research theme is to use inherited cutaneous tumour syndromes to explore fundamental cell signalling pathways in the skin.  There is a strong emphasis on the integration of clinical investigation and basic research as highlighted by a close working relationship between the clinical dermatology and the academic departments, based within the Institute of Cellular Medicine and the Institute of Genetic Medicine.

A strength of this approach is the access to rare skin samples from patients within carefully characterised families who have inherited mutations1.  Application of high-resolution molecular techniques that can characterise the genetic changes in these biological models have led to novel discoveries. Recent work, performed in collaboration with Prof. Alan Ashworth at the Breakthrough Breast Cancer laboratory at London, emphasises this. We discovered dysregulated TRK signalling in skin tumours from patients who carry germline mutations in a tumour suppressor gene CYLD2. This was attactive as TRK represents a kinase that is targettable with existing drugs that have been developed for other purposes. Furthermore, we found that a particular TRK isoform was overexpressed in 70% of basal cell carcinoma, the commonest human cancer. These data highlight how the study of rare models can inform the biology of common cancers. We aim to trial TRK inhibition in CYLD mutation carriers in the future to determine the therapeutic efficacy of this approach in patients.

CYLD defective tumour models also lend themselves to the understanding of tumour patterning in the skin. Using 3D reconstruction techniques of skin tumours in silico, we explored how skin tumours grow and expand at a microscopic level.  By correlating growth patterns with gene expression data, we highlighted Wnt-beta catenin signalling as an important determinant of tumour growth patterns 3.

Our long-term goals are to advance the understanding of cutaneous tumour biology in defined, human, genetic models. We hope to use this data to inform the development of novel treatments for inherited skin tumours. It is anticipated that the discoveries made in these models will continue to inform our understanding of common skin tumours.

 

References

 

1. Rajan N, Langtry JA, Ashworth A, Roberts C, Chapman P, Burn J, et al. Tumor mapping in 2 large multigenerational families with CYLD mutations: implications for disease management and tumor induction. Arch Dermatol 2009;145(11):1277-84.

2. Rajan N, Elliott R, Clewes O, Mackay A, Reis-Filho JS, Burn J, et al. Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours. Oncogene 2011.

3. Rajan N, Burn J, Langtry J, Sieber-Blum M, Lord CJ, Ashworth A. Transition from cylindroma to spiradenoma in CYLD-defective tumours is associated with reduced DKK2 expression. J Pathol 2011;224(3):309-21.

 


Research

 

Please see my research profile for details on the group's research interests.


Key collaborations:

Prof Alan Ashworth - Breakthrough Breast Cancer Research Centre, ICR, Fulham Road, London, UK.

Prof Carol Thiele- NIH, Bethesda, Maryland, USA.

Prof Andor Pivarcsi and Prof. Eniko Sonkoly - Karolinska Institute , Sweden.

 

Current and previous funders:

Wellcome Trust

Medical Research Council

Newcastle Hospital Charities

North East Skin Research Fund

 

Esteem indicators:

Wellcome Trust Intermediate Clinical Fellowship - 2012

Roy Summerly Prize for Best presentation at North of England Dermatology Society meetings (Leeds 2011)

Poster prize Medical Research Society (London 2011)

Highly commended prize MRC Max Perutz Science Writing Award (London 2010)

Best oral presentation in the dermatopathologxy section at the British Association of Dermatologists meeting (Manchester 2010)

Registrar's Prize for the best oral presentation by a trainee in dermatology at the British Society of Investigative Dermatology (Edinburgh 2010)

Best oral presentation in the clinico-pathological cases section at the British Association of Dermatologists meeting (Glasgow 2009)

Medical Research Council Clinical Training Fellowship - 2008

Teaching

 

TEACHING

·   Medical students - Annual sessions since 2004, small group and lecture formats

·   Dental students – Dermatology lectures

·   ST3 paediatric specialist registrar teaching

·   ST3 Medicine teaching in preparation for MRCP

·   MRes student – Benchside teaching

·   GP/General Med SHO teaching – Small group and lecture format

·   Pathology MLSO teaching - Small group format


Publications