Dr Neil Rajan
Wellcome Intermediate Clinical Fellow, Senior Lecturer and Honorary Consultant Dermatologist
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 241 8813
- Fax: +44 (0) 191 241 8666
- Address: Institute of Genetic Medicine
International Centre for Life
Newcastle upon Tyne
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.
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.
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.
Please see my research profile for details on the group's research interests.
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:
Medical Research Council
Newcastle Hospital Charities
North East Skin Research Fund
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
· 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
- Brown S, Ahmed J, Zwolinski S, Brennan P, Rajan N. A novel link between keratoderma and cardiomyopathy: Contiguous gene deletion involving the desmoglein gene cluster. British Journal of Dermatology 2017, epub ahead of print.
- Zangarini M, Rajan N, Danilenko M, Berry P, Traversa S, Veal GJ. Development and validation of LC–MS/MS with in-source collision-induced dissociation for the quantification of pegcantratinib in human skin tumors. Bioanalysis 2017, 9(3), 279-288.
- Bajwa DS, Nasr B, Carmichael AJ, Rajan N. Milia: A useful clinical marker of CYLD mutation carrier status. Clinical and Experimental Dermatology 2017, Epub ahead of print.
- Martin RJ, Arefi M, Splitt M, Redford L, Moss C, Rajan N. Phacomatosis pigmentokeratotica and precocious puberty associated with HRAS mutation. British Journal of Dermatology 2017, epub ahead of print.
- Cranston A, Stocken DD, Stamp E, Roblin D, Hamlin J, Langtry J, Plummer R, Ashworth A, Burn J, Rajan N. Tropomyosin Receptor Antagonism in Cylindromatosis (TRAC), an early phase trial of a topical tropomyosin kinase inhibitor as a treatment for inherited CYLD defective skin tumours: study protocol for a randomised controlled trial. Trials 2017, 18, 111.
- Dubois A, Hodgson K, Rajan N. Understanding Inherited Cylindromas Clinical Implications of Gene Discovery. Dermatologic Clinics 2017, 35(1), 61-71.
- Brown S, Ahmed J, Zwolinski S, Brennan P, Rajan N. A novel contiguous heterozygous deletion involving the desmoglein 2 and desmocollin 2 genes is associated with arrhythmogenic right ventricular cardiomyopathy. In: BAD/RCP Medical Dermatology Meeting. 2016, Royal College of Physicians, London: Wiley-Blackwell Publishing Ltd.
- Rajan N, Sinclair N, Nakai H, Shimomura Y, Natarajan S. A tale of two sisters: identical IL36RN mutations and discordant phenotypes. British Journal of Dermatology 2016, 174(2), 417-420.
- Brown S, Brass D, Rajan N, Oliphant T, Plummer R, Langtry J. Advanced basal cell carcinomas treated by vismodegib and Mohs micrographic surgery: does neoadjuvant treatment have a role?. In: British Association of Dermatologists 96th Annual Meeting. 2016, Birmingham, UK: Wiley-Blackwell.
- Dubois A, Arefi M, Splitt MP, Leech S, Natarajan S, Rajan N. Dry Skin and Blistering in Childhood. Clinical and Experimental Dermatology 2016, 41(7), 828-830.
- Rajan N, Brown S, Ward S, Hainsworth P, Hodgkinson P, Pieniazek P, Husain A, Plummer R. Mesenteric cysts in naevoid basal cell carcinoma syndrome: A mimic of metastatic disease. British Journal of Dermatology 2016, 174(3), 684-685.
- Whitaker S, Leech S, Taylor A, Splitt M, Natarajan S, Rajan N. Multifocal capillary malformations in an older, asymptomatic child with a novel RASA1 mutation. Clinical and Experimental Dermatology 2016, 41(2), 156-158.
- Rajan N, Andersson M, Sinclair N, Fehr A, Hodgson K, Lord C, Kazakov D, Vanecek T, Ashworth A, Stenman G. Overexpression of MYB drives proliferation of CYLD-defective cylindroma cells. In: European Society for Dermatological Research (ESDR) 2016 Annual Meeting. 2016, Munich, Germany: Nature Publishing Group.
- Brown S, Barnard S, Langtry J, Worthy SA, Bloxham C, Loo PS, Husain A, Rajan N. Pulmonary cylindromas in CYLD cutaneous syndrome. In: British Association of Dermatologists 96th Annual Meeting. 2016, Birmingham, UK: Wiley-Blackwell Publishing Ltd.
- Brown S, Worthy SA, Barnard S, Langtry J, Rajan N. Tracking tumour kinetics in patients with germline CYLD mutations. In: British Association of Dermatologists 96th Annual Meeting. 2016, Birmingham, UK: Wiley-Blackwell Publishing Ltd.
- Tang DYL, O'Shea S, Espinoza D, Rajan N, Carmichael A, Newton-Bishop JA. A second family with a telomerase reverse transcriptase (TERT) promoter gene mutation associated with melanomas. In: British Journal of Dermatology. 2015, Manchester, UK: Wiley-Blackwell.
- Dubois A, Wilson V, Bourn D, Rajan N. CYLD Genetic Testing for Brooke-Spiegler Syndrome, Familial Cylindromatosis and Multiple Familial Trichoepitheliomas. PLoS Currents: Evidence on Genomic Tests 2015, 7.
- Kazmierczyk K, Oliphant T, Rajan N, Lawrence C, Langtry J. Sebaceous carcinoma treated by Mohs micrographic surgery: a review of 14 cases. In: British Association of Dermatologists 95th Annual Meeting. 2015, Manchester, UK: Wiley-Blackwell Publishing Ltd.
- Koron S, Leech S, Taylor A, Splitt M, Natarajan S, Rajan N. A novel RASA1 mutation presenting with multiple cutaneous capillary malformations. In: 28th Annual Meeting of the British Society for Paediatric Dermatology. 2014, London: Wiley-Blackwell.
- Brass D, Rajan N, Oliphant TJ, Langtry JAA. Enucleation of cylindromas in Brooke-Spiegler syndrome: a novel surgical technique. In: Abstracts for the British Association of Dermatologists 94th Annual Meeting. 2014, Glasgow: Wiley-Blackwell.
- Rajan N, Sinclair N, Nakai H, Shimomura Y, Natarajan S. Heterozygote IL36RN mutations in a European case of early-onset generalized pustular psoriasis challenge the concept of private mutation. In: British Society of Investigative Dermatology Annual Meeting. 2014, Newcastle upon Tyne: Wiley-Blackwell.
- Tan HY, Kirkham N, Lovat P, Rajan N. Increased p62 expression in CYLD-defective tumours: indication of an autophagic dependency?. In: British Society of Investigative Dermatology Annual Meeting. 2014, Newcastle upon Tyne: Wiley-Blackwell.
- Rajan N, Brown S, Ward S, Pieniazek P, Hainsworth P, Douglas F, Husain A, Plummer R. Mesenteric cysts in Gorlin syndrome: a mimic of metastatic disease. In: Abstracts for the British Association of Dermatologists 94th Annual Meeting. 2014, Glasgow: Wiley-Blackwell.
- Rajan N, Elliott RJR, Smith A, Sinclair N, Swift S, Lord CJ, Ashworth A. The cylindromatosis gene product, CYLD, interacts with MIB2 to regulate Notch signalling. Oncotarget 2014, 5(23), 12126-12140.
- Rajan N, Elliott R, Smith A, Sinclair N, Swift S, Lord C, Ashworth A. The Cylindromatosis gene product, CYLD, interacts with MIB2 to regulate Notch signalling. In: 44th Annual Meeting of the European Society for Dermatological Research. 2014, Copenhagen, Denmark: Nature Publishing Group.
- Rahim RR, Rajan N, Langtry JAA. Infiltrative Recurrent Eccrine Spiradenoma of the Anterior Neck Treated Using Mohs Micrographic Surgery. Dermatologic Surgery 2013, 39(11), 1711-1714.
- Rajan N, Elliot R, Clewes O, Mackay R, Reis-Filho JS, Burn J, Langtry J, Sieber-Blum M, Lord CJ, Ashworth A. Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours. Oncogene 2011, 30(41), 4243-4260.
- 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. Journal of Pathology 2011, 224(3), 309-321.
- Rajan N, Elliott R, Lord CJ, Burn J, Blum MS, Ashworth A. Advances in the development of new therapies for CYLD mutation carriers Targeting Trk. In: Journal of Medical Genetics. 2010, BMJ Publishing Group.
- Rajan N, Elliott R, Lord CJ, Burn J, Sieber-Blum M, Ashworth A. Advances in the development of new therapies for CYLD mutation carriers: Targeting Trk. In: British Society of Human Genetics Annual Conference. 2010, London, UK: BMJ Group.
- Rajan N, Elliott R, Lord C, Clewes O, Burn J, Sieber-Blum M, Ashworth A. Dysregulated tropomyosin receptor kinase (Trk) signalling in CYLD mutant tumours. In: 40th Annual Meeting of the European Society for Dermatological Research. 2010, Nature Publishing Group.
- Rajan N, Wahie S, Seukeran D. Papulonodular eruption, proteinuria, and peripheral arthritis. Papulonodular dermal mucinosis (PDM) in systemic lupus erythematosus. Archives of Dermatology 2010, 146(7), 789-794.
- Rajan N, Gillinder K, Lord C, Langtry JAA, Burn J, Ashworth A, Chaudhury B, Sieber-Blum M. Unravelling cylindromas: insights into appendageal tumour patterning from patients with truncating CYLD mutations. In: 90th Annual Meeting of the British Association of Dermatologists. 2010, Manchester, UK: Wiley-Blackwell Publishing, Inc.
- Rajan N, Bourn D, Roberts C, Langtry JAA, Burn J. A review of seven UK pedigrees with CYLD mutations: clinical implications for mutation carriers. In: 89th Annual Meeting of the British Association of Dermatologists. 2009, Glasgow, UK: Wiley-Blackwell Publishing, Inc.
- Hiscutt E, Rajan N, Panter S, Natarajan S. Demonstration of gastrointestinal venous malformations in Blue Rubber Bleb Naevus Syndrome using capsule endoscopy. Journal of the European Academy of Dermatology and Venereology 2009, 23(3), 322-324.
- Rajan N, Trainer A, Burn J, Langtry J. Familial cylindromatosis and brooke-spiegler syndrome: A review of current therapeutic approaches and the surgical challenges posed by two affected families. Dermatologic Surgery 2009, 35(5), 845-852.
- Rajan N, Das S, Taylor A, Abinun M, Spencer D, Carmichael A. Idiopathic Infantile Pyoderma Gangrenosum with Stridor Responsive to Infliximab. Pediatric Dermatology 2009, 26(1), 65-69.
- Rajan N, Langtry JAA, Ashworth A, Roberts C, Chapman P, Burn J, Trainer AH. Tumor Mapping in 2 Large Multigenerational Families With CYLD Mutations: Implications for Disease Management and Tumor Induction. Archives of Dermatology 2009, 145(11), 1277-1284.
- Rajan N, Powell H, Langtry JAA, Carmichael A, Bourn D, Burn J. Two novel CYLD mutations associated with Brooke-Spiegler syndrome. In: 89th Annual Meeting of the British Association of Dermatologists. 2009, Glasgow, UK: Wiley-Blackwell Publishing, Inc.
- Rajan N, Langtry J, Chapman P, Trainer A, Burn J. Familial cylindromatosis, Brooke-Spiegler syndrome and multiple famililal trichoepithiliomas: Tumour mapping of 26 patients with CYLD mutations suggest androgen stimulation may play a role in tumourigenesis. In: 2008 Annual Meeting. 2008, Nature Publishing Group.
- Rajan N, Langtry JAA. The punch and graft technique: a novel method of surgical treatment for chondrodermatitis nodularis helicis. British Journal of Dermatology 2007, 157(4), 744-747.
- Rajan N, Carmichael AJ, Bramble MG, Hudson M. Cutaneous xanthomatosis: a novel presentation of hypercholesterolaemia in primary sclerosing cholangitis. British Journal of Dermatology 2006, 155(1), 223-225.
- Rajan N, Langtry JA. Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas. Clinical and Experimental Dermatology 2006, 31(1), 140-141.
- Rajan N, Ryan J, Langtry JA. Squamous cell carcinoma arising within a facial port-wine stain treated by Mohs micrographic surgical excision. Dermatologic Surgery 2006, 32(6), 864-866.