Professor Charlotte Proby

Professor of Dermatology

Understanding the molecular and biological drivers of cutaneous squamous cell carcinoma

Address:

Division of Cancer Research
Jacqui Wood Cancer Centre
University of Dundee
James Arrott Drive
Ninewells Hospital And Medical School
Dundee
DD1 9SY

Phone Number:

+(44) 01382 383289

Email Address:

c.proby@dundee.ac.uk

Biography

Professor Proby graduated in Medicine from Oxford University and The Middlesex Hospital, London, in 1982. She entered Dermatology in 1987 (St Georges Hospital, London), becoming a clinical research fellow in 1989 with Professor Irene Leigh (The Royal London Hospital). She undertook clinical training in photobiology (St John’s Institute of Dermatology 1992-1994), before rejoining Barts and the London School of Medicine and Dentistry (BLSMD) as a Senior Lecturer in Dermatology in 1994.  Professor Proby was Senior Lecturer at BLSMD establishing a longitudinal cohort study of skin cancer in organ transplant recipients and leading the clinical programme for the Cancer Research UK Skin Tumour Laboratory. She was awarded FRCP in 2004 and then moved to Dundee as Clinical Reader in 2007. 

Since her move to Dundee, she has been appointed Secretary of the Scottish Dermatological Society Skin Cancer Group, President of the British Society for Skin Care in Immunosuppressed Individuals, Chair of the Scottish Intercollegiate Guidelines Network for cutaneous Squamous Cell Carcinoma (SIGN SCC), member of the NCRI non-melanoma skin cancer clinical studies group, member of the British Association of Dermatologists Skin Cancer Prevention Committee, Board member of Skin Care in Organ transplant Patients in Europe (SCOPE) and UK representative on the International Transplant Skin Cancer Collaboration (ITSCC).

Research

Professor Proby’s research has focused on skin cancer, particularly on cutaneous squamous cell carcinoma (SCC).  Cutaneous SCC, the second most common cancer in white skinned human populations, is rapidly increasing in incidence in our sun-damaged and aging population. It is a significant challenge in high-risk populations such as immunosuppressed organ transplant recipients (OTR) who show a 150-fold increased risk for SCC, often developing multiple cancers with significant morbidity and mortality.  

She has made major contributions to research in non-melanoma skin cancer and is recognized as an international leader in the causes and prevention of transplant skin cancers.  She has investigated the role of human papillomaviruses (HPV) in transplant SCC with both epidemiological and functional studies establishing an important co-factor or facilitatory role for HPV. Recently, her research has focused more on the molecular mechanisms driving SCC and the identification of biomarkers and therapeutic targets. She is currently involved with target identification, target validation and trials of targeted therapies in in vitro and in vivo models of skin cancer prior to translation into human trial.  She is actively involved in clinical trials of new topical therapies for skin cancer and in public and GP education for skin cancer prevention and early detection.

She has an increasingly important role in melanoma research in Scotland, with a current focus on the discovery and validation of serum epigenetics as prognostic biomarkers for melanoma metastasis.  In addition, we now have a new clinical trial (first in UK) for use of MEK inhibitor in NRAS-mutation positive melanoma (NEMO trial) due to start Dec 2013 and are in discussions with Novartis for an investigator-initiated ‘first of its kind’ use of combination BRAF-inhibitor and MEK-inhibitor for BRAF-positive melanoma in the adjuvant setting.

She is increasingly involved in the Wellcome Trust-funded strategic award, so-called ‘DGEM’ initiative (Dermatology and Genetic Medicine; £5.9M; Grant holders Irwin MacLean, Irene Leigh, John McGrath), providing clinical expertise for the drug-discovery component and helping to build a clinical network for genetic skin diseases across the UK (BADGEM). In particular, she is facilitating the development of a Genetic Skin Disease registry within Dundee Health Informatics Centre (HIC) and she is applying for funding to develop a Scottish Clinical Trials Unit for Genetic Skin Disease to be based at the Clinical Research Centre (CRC) within Ninewells Hospital & Medical School. We aim to become a preeminent clinical centre in the UK for Genetic Skin Diseases as we already are for skin cancer research and treatment, and for photodermatology and phototherapy. 

Professor Proby currently has programme grant funding from Cancer Research UK, with project grants from British Skin Foundation, NIHR Research for Patient Benefit and Focus on Melanoma.

Publications

Recent publications:

South AP, Purdie KJ, Watt SA, Haldenby S, den Breems NY, Dimon M, Arron ST, Kluk MJ, Aster JC, McHugh A, Xue DJ, Dayal JH, Robinson KS, Rizvi SM, Proby CM, Harwood CA, Leigh IM. NOTCH1 Mutations Occur Early during Cutaneous Squamous Cell Carcinogenesis. J Invest Dermatol. 2014 Mar 24.

Bouwes Bavinck JN, Harwood CA, Genders RE, Wisgerhof HC, Plasmeijer EI, Mitchell L, Olasz EB, Mosel DD, Pokorney MS, Serra AL, Feldmeyer L, Baumann Conzett K, Piaserico S, Belloni Fortina A, Jahn K, Geusau A, Gerritsen MJ, Seckin D, Gulec AT, Cetkovska P, Ricar J, Imko-Walczuk B, Proby CM, Hofbauer GF.  Pain identifies squamous cell carcinoma in organ transplant recipients: the SCOPE-ITSCC PAIN study. Am J Transplant. 2014 Mar;14(3):668-76.

Lambert, SR; Mladkova, N; Gulati, A; Hamoudi, R; Purdie, K; Cerio, R; Leigh, I; Proby, C; Harwood, CA; Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling; 2014 January 21; 110(2) 520-529.

Seçkin D, Barete S, Euvrard S, Francès C, Kanitakis J, Geusau A, Del Marmol V, Harwood CA, Proby CM, Ali I, Güleç AT, Durukan E, Lebbé C, Alaibac M, Laffitte E, Cooper S, Bouwes Bavinck JN, Murphy GM, Ferrándiz C, Mørk C, Cetkovská P, Kempf W, Hofbauer GF. Primary cutaneous posttransplant lymphoproliferative disorders in solid organ transplant recipients: a multicenter European case series.  Am J Transplant. 2013 Aug;13(8):2146-53.

Matin RN, Chikh A, Law Pak Chong S, Mesher D, Graf M, Sanza P, Senatore V, Scatolini M, Moretti F, Leigh IM, Proby CM, Costanzo A, Chiorino G, Cerio R, Harwood CA, Bergamaschi D.  p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.  J Exp Med. 2013 Mar 11;210(3):581-603.

Nigro CL, Wang H, McHugh A, Lattanzio L, Matin R, Harwood C, Syed N, Hatzimichael E, Briasoulis E, Merlano M, Evans A, Thompson A, Leigh I, Fleming C, Inman GJ, Proby C, Crook T. Methylated Tissue Factor Pathway Inhibitor 2 (TFPI2) DNA in serum is a novel biomarker of metastatic melanoma. J Invest Dermatol. 2013 May;133(5):1278-85.

Neale RE, Weissenborn S, Abeni D, Bouwes Bavinck JN, Euvrad S, Feltkamp MC, Green AC, Harwood CA, de Koning MN, Naldi L, Nindl I, Pawlita M, Proby C, Quint W, Waterboer T, Wieland U, Pfister HJ.  Human Papillomavirus load in eyebrow hair follicles and risk of cutaneous squamous cell carcinoma.  Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):719-27.

Hoogendijk-van den Akker JM, Harden PN, Hoitsma AJ, Proby CM, Wolterbeek R, Bouwes Bavinck JN, de Fijter JW. Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus.  J Clin Oncol. 2013 Apr 1;31(10):1317-23.

*Harwood CA, Mesher D, McGregor JM, Mitchell L, L-Green M, Raftery M, Cerio R, Leigh IM, Sasieni P, Proby CM.  A surveillance model for skin cancer in organ transplant recipients: A 22-year prospective study in an ethnically diverse population.  Am J Transplant. 2013 Jan;13(1):119-29.

Verschooten L, Barrette K, Van Kelst S, Rubio Romero N, Proby C, de Vos R, Agostinis P, Garmyn M.  Autophagy inhibit chloroquine enhanced the cell death inducing effect of the flavonoid Luteolin in metastatic squamous cell carcinoma cells.  PLoS One 2012; 7(10): e48264 Epub 2012 Oct 26.

*de Vries E, Trakatelli M, Kalabalikis D, Ferrandiz L, Ruiz-de-Casas A, Moreno-Ramirez D, Sotiriadis D, Ioannides D, Aquilina S, Apap C, Micallef R, Scerri L, Ulrich M, Pitkänen S, Saksela O, Altsitsiadis E, Hinrichs B, Magnoni C, Fiorentini C, Majewski S, Ranki A, Stockfleth E, Proby C; EPIDERM Group. Known and potential risk factors for skin cancer in European populations: a multicentre case-control study.  Br J Dermatol. 2012 Aug;167 Suppl 2:1-13.

Flohil SC, Proby CM, Forrest AD, van Tiel S, Saksela O, Pitkänen S, Ahti T, Micallef R, de Vries E; EPIDERM Group. Basal cell carcinomas without histological confirmation and their treatment: an audit in four European regions.  Br J Dermatol. 2012 Aug;167 Suppl 2:22-8

Ferrandiz L, Ruiz-de-Casas A, Trakatelli M, de Vries E, Ulrich M, Aquilina S, Saksela O, Majewski S, Ranki A, Proby C, Magnoni C, Pitkänen S, Kalokasidis K, Siskou S, Hinrichs B, Altsitsiadis E, Stockfleth E, Moreno-Ramirez D; EPIDERM Group. Assessing physicians’ preferences for skin cancer treatment in Europe.  Br J Dermatol. 2012 Aug;167 Suppl 2:29-35.

Traianou A, Ulrich M, Apalla Z, De Vries E, Bakirtzi K, Kalabalikis D, Ferrandiz L, Ruiz-de-Casas A, Moreno-Ramirez D, Sotiriadis D, Ioannides D, Aquilina S, Apap C, Micallef R, Scerri L, Pitkänen S, Saksela O, Altsitsiadis E, Hinrichs B, Magnoni C, Fiorentini C, Majewski S, Ranki A, Proby CM, Stockfleth E, Trakatelli M; EPIDERM Group.  Risk factors for actinic keratosis in eight European centres: a case-control study.  Br J Dermatol. 2012 Aug;167 Suppl 2:36-42.

Trakatelli M, Siskou S, Proby C, Tiplica GS, Hinrichs B, Altsitsiadis E, Kitsou A, Ferrandiz L, Aquilina S, Apap C, Ulrich M, Fiorentini C, Magnoni C, de Vries E, Flohil SC, Kalokasidis K, Moreno-Ramirez D, Ruiz-de-Casas A, Majewski S, Ranki A, Pitkänen S, Saksela O, Ioannides D, Sotiriadis D, Stockfleth E; EPIDERM.  The patient journey: a report of skin cancer care across Europe.  Br J Dermatol. 2012;167 Suppl 2:43-52.

Lo Nigro C, Monteverde M, Lee S, Lattanzio L, Vivenza D, Comino A, Syed N, McHugh A, Wang H, Proby C, Garrone O, Merlano M, Hatzimichael E, Briasoulis E, Gojis O, Palmieri C, Jordan L, Quinlan P, Thompson A, Crook T. NT5E CpG island methylation is a favourable breast cancer biomarker.  Br J Cancer 2012 Jun26; 107(1): 75-83.

Barrette K, Zutterman N, Van Kelst S, Proby C, Garmyn M. Pattern of sensitivity of progressive cutaneous squamous cell carcinoma cells to UVB and oxidative stress induced cell death. Photochem Photobiol Sci. 2013 Jan;12(1):104-10.

Hack K, Reilly L, Proby C, Fleming C, Leigh I, Foerster J.  Wnt5a inhibits the CpG oligodeoxynucleotide-triggered activation of human plasmacytoid dendritic cells.  Clin Exp Dermatol 2012; 37(5): 557-61.

Jian Li, Kai Wang, Fei Gao, Thomas D. Jensen, Shengting T. Li, Paula M. DeAngelis, Steen Kølvraa, Charlotte Proby, Ola Forslund, Lars Bolund and Ole Petter F. Clausen. Array Comparative Genomic Hybridization of Keratoacanthomas and Squamous Cell Carcinomas: Different Patterns of Genetic Aberrations Suggest Two Distinct Entities. J Invest Dermatol 2012 Aug; 132(8): 2060-6. doi: 10.1038/jid.2012.104. [Epub 2012 Apr 26].

Clayburgh DR, Gross ND, Proby CM, Koide J, Wong MH.  The Effects of Epidermal Growth Factor Receptor and Insulin-like Growth Factor 1 Receptor inhibition on proliferation and intracellular signaling in cSCCHN: Potential for Dual Inhibition As a Therapeutic Modality. Head Neck. 2012 Apr 12. doi: 10.1002/hed.22936. [Epub ahead of print].

Wang H, Lee S, Nigro CL, Lattanzio L, Merlano M, Monteverde M, Matin R, Purdie K, Mladkova N, Bergamaschi D, Harwood C, Syed N, Szlosarek P, Briasoulis E, McHugh A, Thompson A, Evans A, Leigh I, Fleming C, Inman GJ, Hatzimichael E, Proby C, Crook T. NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity.  Br J Cancer 2012; 106(8): 1446-52.

*de Vries E, Micallef R, Brewster DH, Gibbs JH, Flohil SC, Saksela O, Sankila R, Forrest AD, Trakatelli M, Coebergh JW, Proby CM; EPIDERM Group. Population-based estimates of the occurrence of multiple vs first primary basal cell carcinomas in 4 European regions.  Arch Dermatolol 2012; 148(3): 347-54.

Pourreyron C, Reilly L, Proby C, Panteleyev A, Fleming C, McLean K, South AP, Foerster J.  Wnt5a is strongly expressed at the leading edge in non-melanoma skin cancer, forming active gradients, while canonical Wnt signalling is repressed.  PLoS One 2012; 7(2): e31827.

*Lambert SR, Harwood CA, Purdie KJ, Gulati A, Matin RN, Romanowska M, Cerio R, Kelsell DP, Leigh IM, Proby CM.  Metastatic cutaneous squamous cell carcinoma shows frequent deletion in the protein tyrosine phosphatase receptor type D gene. Int J Cancer. 2012 Aug 1;131(3):E216-26. doi: 10.1002/ijc.27333.

Cheung BB, Koach J, Tan O, Kim P, Bell JL, D'andreti C, Sutton S, Malyukova A, Sekyere E, Norris M, Haber M, Kavallaris M, Cunningham AM, Proby CM, Leigh I, Wilmott JS, Cooper CL, Halliday GM, Scolyer RA, Marshall GM. The retinoid signaling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro. J Pathol. 2012 Feb;226(3):451-62.

Wang NJ, Sanborn Z, Arnett KL, Bayston LJ, Liao W, Proby CM, Leigh IM, Collisson EA, Gordon PB, Jakkula L, Pennypacker S, Zou Y, Sharma M, North JP, Vemula SS, Mauro TM, Neuhaus IM, Leboit PE, Hur JS, Park K, Huh N, Kwok PY, Arron ST, Massion PP, Bale AE, Haussler D, Cleaver JE, Gray JW, Spellman PT, South AP, Aster JC, Blacklow SC, Cho RJ.  Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma.  Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17761-6.

Sampogna F, Bouwes Bavinck JN, Pawlita M, Abeni D, Harwood C, Proby CM, Feltkamp M, Euvrard S, Naldi L, Neale R, Nindl I, Pfister H, Quint W, Waterboer T.  Factors associated with the seroprevalence of 26 cutaneous and two genital human papillomavirus types in organ transplant patients. J Gen Virol. 2012 Jan; 93:165-74.

Weissenborn S, Neale RE, Waterboer T, Abeni D, Bavinck JN, Green AC, Harwood CA, Euvrard S, Feltkamp MC, de Koning MN, Naldi L, Quint WG, Tessari G, Proby CM, Wieland U, Pfister H; EPI-HPV-UV-CA group.  Beta-papillomavirus DNA loads in hair follicles of immunocompetent people and organ transplant recipients. Med Microbiol Immunol. 2012 May; 201(2): 117-25.

Wang NJ, Sanborn Z, Arnett KL, Bayston LJ, Liao W, Proby CM, Leigh IM, Collisson EA, Gordon PB, Jakkula L, Pennypacker S, Zou Y, Sharma M, North JP, Vemula SS, Mauro TM, Neuhaus IM, Leboit PE, Hur JS, Park K, Huh N, Kwok PY, Arron ST, Massion PP, Bale AE, Haussler D, Cleaver JE, Gray JW, Spellman PT, South AP, Aster JC, Blacklow SC, Cho RJ.  Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma.  Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17761-6.

Proby CM, Harwood CA, Neale RE, Green AC, Euvrard S, Naldi L, Tessari G, Feltkamp MCW, de Koning MNC, Quint WGV, Waterboer T, Pawlita M, Weissenborn S, Wieland U, Pfister H, Stockfleth E, Nindl I, Abeni D, ter Schegget J, Bouwes Bavinck JN, and the EPI-HPV-UV-CA group. A case-control study of betapapillomavirus infection and cutaneous squamous cell carcinoma in organ transplant recipients. American Journal Transplantation 2011; 11: 1498-508

Purdie KJ, Harwood CA, Gibbon K, Chaplin T, Young BD, Cazier JB, Singh N, Leigh IM, Proby CM.  High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia.  Br J Cancer 2010; 102(6): 1044-51

Purdie KJ, Harwood CA, Gulati A, Chaplin T, Lambert SR, Cerio R, Kelly G, Cazier JB, Young BD, Leigh IM, Proby CM. SNP array analysis defines a specific genetic fingerprint for well-differentiated SCC. J Invest Dermatol 2009 Jun;129(6):1562-8.

Brown VL, Atkins CL, Ghali L, Cerio R, Harwood CA, Proby CM.   Safety and Efficacy of 5% Imiquimod Cream for the Treatment of Skin Dysplasia in High Risk Renal Transplant Recipients: Randomised, Double-Blind, Placebo-Controlled Trial.  Arch Dermatol 2005; 141: 985-993

Harwood CA, Leedham-Green M, Leigh IM, Proby CM. Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study. Arch Dermatol 2005; 141(4): 456-64

Brown VL, Harwood CA, Cronin J, Crook T, Kelsell D, Proby CM. p16INK4a and p14ARF tumour suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma. J Invest Dermatol 2004;122:1284-92

Teaching

Professor Proby plays an active teaching and mentoring role within the University, within the NHS, nationally and internationally.  She has fostered the research careers of many clinical academics in Dermatology through supervision of clinical research fellowships and she actively mentors junior academic colleagues.  In the last two years, she has developed a national GP Toolkit to help GPs recognise skin lesions that need referral through the urgent 2-week pathway. Since 2010, as part of a European collaboration, she has delivered skin cancer teaching across Europe.

* In addition to routine undergraduate teaching, teaching of student-selected components, and supervisor for year 4 medical student projects, she has joined an innovative teaching team within dermatology at Ninewells. This builds on her previous commitment to teaching whilst a Senior Lecturer at Barts & the London, where she modernised the Dermatology Undergraduate Curriculum introducing a Clinical Skills component, an on- line 'Learning Landscape', and exam questions.

* Dermatology undergraduate teaching in Dundee was the highest or second highest scoring undergraduate course in 2009, 2010 and 2011.

* As a Medical School Tutor, she undertakes weekly review of patient case history submissions for student portfolios with electronic Feedback and regular tutorials.

* Medical Student Projects – She regularly supervises one or two medical students undertaking 4th year student projects. The most recent project involved an education intervention in Dundee high schools with pre- and post-assessment of student knowledge/understanding and behaviour with regard to sun damage, sun protection and skin cancer.  This conclusively showed that such an intervention increases knowledge but does not influence behaviour and therefore is not by itself a sufficient skin cancer prevention strategy.

* She teaches GPs on an annual GP Registrar training (2 days); at the twice annual GP Skin Forum; and, through a joint Cancer Research UK-British Association of Dermatologists-Department of Health initiative, she takes a leading role in developing an on-line skin cancer detection “GP Toolkit” which is currently live on the doctors.org.uk website.

PhD Supervision

Hexiao Wang – “Epigenetic Dysregulation of Novel Candidate Genes in Melanoma” Main supervisor. - successful completion of PhD and graduation, Submitted August 13, Examined October 2013, Graduation November 2013

Dr Aidan Rose – Dundee Cancer Centre Clinical PhD student, started Sept 2012, co-supervisor

Catriona Harkins – Wellcome Trust Clinical PhD student, started September 2013, co-supervisor

Dr Nikol Mladkova – PhD funded by British Skin Foundation; 2009-13, co-supervisor

Past students

  • Dr Catherine Harwood; MRC Clinical Training Fellow; awarded PhD 2002 (main supervisor)
  • Dr Victoria Brown; MRC Clinical Training Fellow; awarded MD 2006 (main supervisor)
  • Dr Victoria Swale; Bobby Moore Fellowship (CR-UK); awarded MD 2006 (co-supervisor)
  • Dr Ferina Ismail; MRC Clinical Training Fellow; awarded PhD 2008 (co-supervisor)
  • Dr Conal Perrett; CR-UK Clinical Training Fellow; awarded PhD 2008 (co-supervisor)
  • Ms Delphine Casabonne; CR-UK PhD student (part-time); awarded PhD 2009 (main supervisor)
  • Dr Rubeta Matin: MRC Clinical Training Fellow; awarded PhD 2010 (co-supervisor)
  • Ms Sally Lambert; CR-UK PhD Student, 2005-9; Awarded PhD 2010 (main supervisor)
  • Dr Abha Gulati; Clinical Training Fellow, 2006-9; Awarded PhD 2010 (main supervisor)

Conferences

Recent Invited Lectures:

Prevention and Screening Research Group (CRiPS), Dundee, December 2013

National Cancer Research Institute (NCRI) Annual meeting, Liverpool, November 2013

Scottish Dermatology Society Training Symposium, Dundee, October 2013

International Investigative Dermatology Mentors Dinner, Edinburgh, May 2013

International Transplant Skin Cancer Collaboration, Boston, USA October 2012

British Association of Dermatologists Annual Meeting, Birmingham, UK July 2012

Skin Care in Organ Transplant recipients (SCOPE) Istanbul, Turkey, May 2012

Royal College of Physicians (RCP) Medical Dermatology meeting, London, Jan 2012

UK Dermatology Translational Research Network inaugural meeting, London, Nov 2011 European Academy of Dermatology and Venereology, Lisbon, Portugual, Oct 2011

Dundee-Belfast Cancer Centre Joint symposium, Dundee, May 2011

Association of Physicians Annual Meeting (APAM), Dundee, UK, April 2010

The Fleming Lecture, Royal College of Physicians and Surgeons, Glasgow, May 2010

Invited Speaker and Expert Panel: British Association of Dermatologists Skin Cancer Symposium, Royal Society of Medicine (RSM), London, October 2010

Invited Speaker, International Melanoma Congress, The Netherlands, 2009.

Invited Speaker, Dermatology Update for Physicians and GPs (RSM) London, 2009

Guest Lecture, Scottish Dermatological Society President’s symposium, Edinburgh, April 2008

Guest Lecture, British Association of Dermatologists Annual Meeting, Manchester, July 2008

Invited Speaker, Medical Dermatology symposium (RCP), London, 2006, 2007