Professor Martin Thornhill MBBS, BDS, PhD, MSc, FDSRCS(Edin), FDSRCSI, FDSRCS(Eng)

Professor of Oral Medicine

Tel: +44 (0)114 271 7857
Fax: +44 (0)114 271 7863
Email:   m.thornhill@sheffield.ac.uk

Research Interests

My research focuses on innate and immune responses to environmental influences, such as microbial pathogens, and to diseases, such as head and neck cancer and the mucocutaneous diseases. I am engaged in fundamental research into theinteractions that occur between cells during these disease processes and translational studies that will take our discoveries into therapeutic clinical trials to improve the outcome for patients. Currently, I have four major areas of research activity:

Tissue engineering, biocompatibility and in vitro modelling of disease

We continue to research the biology of normal oral mucosa and skin in order to develop more complex 3 dimensional tissue engineered constructs of these tissues. These are used to study the tissue responses to biomaterials, fungi and bacteria as well methods of drug delivery across the skin and oral mucosa. In addition, the constructs are used for in vitro modelling of various skin and mucosal diseases. These include, head and neck cancer, the autoimmune bullous diseases, lichen planus, oral candidiasis, oral mucositis, oral ulceration, gingivitis and wound healing. These models enable us to investigate and better understand the mechanisms responsible for these diseases and to develop new diagnostic procedures and treatments without the need for animal studies.

See:

Centre for Biomaterials and Tissue Engineering - Tissue engineering of oral mucosa

Centre for Biomaterials and Tissue Engineering - Biocompatibility testing and evaluation

We are also developing in vitro models of solid cancers such as head and neck cancer. In patients, these cancers develop as an expanding mass of cells that become more and more hypoxic at their core. The hypoxic centres are often resistant to radio- and chemo-therapy while the expanding ball of tumour cells induces the formation of blood vessels and displaces or invades surrounding tissue. In order to study the interaction of tumour cells with their surrounding tissue, we are growing 3 dimensional tumour spheroids in vitro that replicate the properties of malignant tumour growth. Using tumour spheroids, we can study the normal tissue response to tumours and develop new and improved treatments.

Centre for Biomaterials and Tissue Engineering - Tissue engineering of oral mucosa

Cellular interactions with the endothelial lining of blood vessels

Endothelial cells line blood vessels and regulate the passage of cells from the circulation into the tissues. This important 'gate keeper' function allows them to regulate many physiological and disease processes. However, this is a very dynamic process with circulating cells normally interacting with endothelium under conditions of flow. However, most studies of how cells interact with endothelium are performed under static conditions and this does not replicate what happens in vivo. To replicate what happens in life, we use flow assays in which we can study how cells interact with endothelial cells under conditions of flow. Currently, we are using these assays to study how adhesion molecules regulate the adhesion of leukocytes, tumour cells and micro-organisms to endothelial cells and thereby control their homing and dissemination to different sites in the body.

Centre for Biomaterials and Tissue Engineering - Tissue engineering of blood vessels

Targeted drug delivery

We are also using tissue and disease models to test and develop smart drug delivery systems. By combining our knowledge of tissue specific markers and smart drug encapsulation systems we are developing the means to selectively deliver payloads of genes, radioisotopes and drugs into target cells whilst avoiding other tissues in the body. Using our model systems we can rigorously test the selectivity and effectiveness of these smart drug delivery systems before moving to clinical trials. In particular, we are working with colleagues in the Center for Tissue Engineering and Biomaterials to develop synthetic self assembling nanoparticle polysome delivery systems that will encapsulate genes, drugs and radioisotopes and deliver them into the cells themselves. By coating the surface of these polymersomes with appropriate ligands we can selectively target their uptake into specific tissues or cancer cells so that only the diseased cells receive treatment and the rest of the body is not exposed to the toxic side effects of these drugs.

See:

Centre for Biomaterials and Tissue Engineering -Tissue engineering of oral mucosa

Genetic epidemiology of oral disease

Many oral diseases are multi-factorial in origin, often having both environmental and complex genetic factors involved in their aetiology. Using modern genetic epidemiological approaches, it is possible nowadays to identify gene polymorphisms, and other genetic factors, that predispose a particular individual to disease. Identifying these genetic factors often provides an important insight into the disease process, provides a means for identifying individuals at risk for the disease and helps to identify new approaches for treating the disease. We are therefore using genetic epidemiological studies of a number of common oral diseases, including facial pain syndromes, periodontal disease, oral lichen planus and recurrent aphthous stomatitis to better understand these conditions.

Recent Publications

Moharamzadeh K., Brook I.M., Van Noort R., Scutt A.M. and Thornhill M.H. (2007). Tissue engineered oral mucosa: a review of the scientific literature. J. Dent. Res. 86:115-124.

Thornhill M.H., Sankar V., Xu X-J., Barrett W.A., High A.S., Odell E.W., Speight P.M. and Farthing P.M. (2006). The role of histopathological characteristics in distinguishing amalgam-associated oral lichenoid reactions and oral lichen planus. J. Oral Pathol. Med. 35:233-40.

Papagerakis S., Berdal A., Shabana A.H., Thornhill M.H. and Depondt J. (2006). ?–catenin expression and function in oral cancer. Oral Oncology 11:54-60.

Thornhill M.H. (2006). Oral lichenoid lesions and amalgam fillings. Evidence-Based Dentistry. 7(3):74-5,.

Zakrzewska J.M., Chan E.S-Y, and Thornhill M.H. (2005) A sytematic review of placebo controlled, randomised trials of treatments used for oral lichen planus. Br. J. Dermatol. 153:336-341.
Healy C.M., Williams D.M. and Thornhill M.H. (2004). Haematinic deficiency in recurrent aphthous stomatitis, it prevalence and response to treatment. Oral Biol. Med. 1:259-266.

Karasneh J., Hajeer A.H., Barrett J., Ollier W.E.R., Thornhill M. and Gul A. (2003) Association of specific Interleukin 1 gene cluster polymorphisms with increased susceptibility for Behçet´s disease. Rheumatology. 42:860-864.

Little M.C., Griffiths C.E.M., Watson R.E.B., Pemberton M. and Thornhill M.H. (2003) Oral mucosal keratinocytes express RANTES and ICAM-1, but not interleukin-8, in oral lichen planus and oral lichenoid reactions induced by amalgam fillings. Clin. Exp. Dermatol. 28:64-69.

Thornhill M.H., Pemberton M.N., Symonds R.K., and Theaker E.D. (2003) Amalgam contact hypersensitivity lesions and oral lichen planus. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 95:291-299.

Bazrafshani M.R., Hajeer A.H., Ollier W.E.R. and Thornhill M.H. (2003) Polymorphisms in the IL-10 and IL-12 gene cluster and risk of developing recurrent aphthous stomatitis. Oral Diseases 9:287-291.

Atkin P.A., Xu X-J. and Thornhill M.H. (2002) Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine. Oral Diseases 8:173-176.

Bazrafshani M.R., Hajeer A.H., Ollier W.E.R. and Thornhill M.H. (2002) IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS). Genes & Immunity. 3:302-305.

Pemberton M.N., Sarrami N., Thornhill M.H. and Theaker E.D. (2002) Adverse reactions associated with the use of eugenol in dentistry. Br. Dent. J. 193(5):257-259.

Bazrafshani M.R., Hajeer A.H., Ollier W.E.R. and Thornhill M.H. (2002) Recurrent aphthous stomatitis and gene polymorphisms for the inflammatory markers TNF?, TNF? and the Vitamin D receptor: no association detected. Oral Diseases. 8:303-307.

Pemberton M.N., Dewi P.S., Hindle I. and Thornhill M.H. (2001) The Investigation and medical management of trigeminal neuralgia by consultant oral and maxillofacial surgeons in the British Isles. Br. J. Oral Maxillofacial Surg. 39:114-119.

Thornhill M.H. (2001) Immune mechanisms in oral lichen planus. Acta Odont. Scand. 59:174-177.

Simons D., Thornhill M.H. and Murray S. (2001) The hygienists role in the management of a patient with dermatitis herpetiformis. Dental Health. 40:8-11.

Little M.C., Griffiths C.E.M., Watson R.E.B., Pemberton M. and Thornhill M.H. (2001) Activation of oral keratinocytes by mercuric chloride: relevance to dental amalgam-induced oral lichenoid reactions. Br. J. Dermatol. 144:1024-1032.

Pemberton M. and Thornhill M.H. (2001) British general practitioners´ experience and knowledge of xerostomia – A retrospective study. International Journal of Health Promotion & Education. 39:86-87.

McGiven B., Pemberton M., Theaker E.D., Buchanan J.A.G. and Thornhill M.H. (2000) Delayed and immediate hypersensitivity reactions associated with the use of amalgam. Br. Dent. J. 188:73-76.

Chan E.S., Thornhill M. and Zakrzewska J. (2000) Little strong evidence to base treatment of symptomatic lichen planus. A summary by George T Gallagher. Evidence-Based Dentistry 2:14.

Healy C.M., Cruchley A.T., Thornhill M.H., and Williams D.M. (2000) The effect of sodium lauryl sulfate, triclosan and zinc on the permeability of normal oral mucosa. Oral Diseases 6:118-123.

Atherton G.J., Pemberton M.N. and Thornhill M.H. (2000) Medical emergencies: the experience of staff of a UK dental teaching hospital. Br. Dent. J. 188:320-324.

Chan E.S., Thornhill M. and Zakrzewska J. (2000) Interventions for treating oral lichen planus. Cochrane Database Syst Rev 2000;(2):CD001168

Thornhill M., Pemberton M., Buchanon J. and Theaker E. (2000) An open clinical trial of sulphamethoxypyridazine in the treatment of mucous membrane pemphigoid. Br. J. Dermatol. 143:117-126.

Pemberton M.N., Atherton G.J. and Thornhill M.H. (2000) Violence and aggression at work. Br. Dent. J. 189:409-410.

Li J., Farthing P.M. and Thornhill M.H. (2000) Oral and skin keratinocytes are stimulated to secrete monocyte chemattractant protein-1 by tumour necrosis factor-[alpha] and interferon-[gamma]. J. Oral Pathol. Med. 29:438-44.

Li J. and Thornhill M.H. (2000) Growth-regulated peptide-[alpha] (GRO-[alpha]) production by oral keratinocytes: a comparison with skin keratinocytes. Cytokine. 9:1409-1413.

Personal Web Link

Centre for Biomaterials and Tissue Engineering - Personal web page