Dermatology, Skin and Environment Interactions Group
A key aim of this research group is to understand the skins responses to environmental signals (including drugs, chemicals, foreign antigens and ultraviolet radiation).
Major themes of research include:
- Cell signalling mechanisms activated by physiological and pathological environmental stress – including ultraviolet radiation and mechanical stress.
- Functional consequences of interplay between environmental and genomic elements in cell biology .
- Pathogenesis, molecular and signalling mechanisms of inflammatory skin disease, skin cancer and ageing.
- Genetic factors underlying inter-individual responses of the skin to environmental factors.
- Clinical, translational and therapeutic research (including pharmacogenetics) of inflammatory skin disease (eg psoriasis and atopic eczema) and skin cancer.
- Cutaneous immunology.
- Stem cell research.
Approaches and expertise
There is a strong emphasis on inter-disciplinary working and 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.
We encourage imaginative and multidisciplinary approaches and have particular expertise in translational medicine (in vivo studies, bio-bank, therapeutics, skin equivalents), stem cell biology, imaging (live cell, confocal, high-content, in vivo), UV irradiation (dosimetry, action spectra and human exposure), cell signalling and the analysis of cellular, mitochondrial and nuclear responses.
Key Collaborations
We foster a vibrant, interactive and collaborative environment as evidenced by multiple joint grants, joint supervision of research students and scientific publications. The group comprises Principal Investigators(PIs) from Dermatology, Pharmacology, Haematology, Toxicology and Medical Physics all within ICM. In addition, Principal Investigators have collaborations across other research institutes (eg IAH, ICAMB, IHG, NESCI, NICR) and research groups (eg Cell Signalling, Nanotechnology).
Our research environment is enhanced by key external collaborations promoting exchange of ideas and expertise. These include links within and outwith UK/Europe:
- University of Durham,
- University of Rome,
- Mount Sinai School of Medicine,
- New York Singapore Immunology Network and,
- The Hospital for Sick Children, Toronto.
Postgraduate training
We place a strong emphasis on postgraduate training and have an active weekly programme both within ICM and dermatology (clinical and basic science journal clubs, research in progress meetings) and play a key role in running the MRes in Medical and Molecular Biosciences.
Many of our clinical trainees pursue higher research degrees funded through external nationally funded fellowships and our PhD students have secured both prestigious fellowships (European Commission) and post-doctoral positions (eg Khavari lab, Stanford; Buck Institute, San Francisco; NIH, Bethesda; University of Chicago). In 2006/2007 we were one of only three units in England and Wales to be awarded academic clinical fellowships in dermatology through a national competition and a Walport/NIHR Lectureship was recently established.
Dermatology is one of six priority areas supported through a Wellcome Clinical Research Training Fellowship Scheme in Translational Medicine and Therapeutics at Newcastle University which provides up to four fellowships per year for the next five years. This scheme is designed principally to provide training for clinicians in translational research to PhD level in Newcastle.
Engagement
We encourage relevant commercialisation of our research through both consultancy and the establishment of spin out companies such as Genesis Genomics UK (2002) which has attracted significant government and private funding.
Our research is supported by key links and industrial collaborations (eg Stiefel UK, BBSRC CASE studentships with Unilever, AstraZeneca, and Procter and Gamble) and links with regional funding agencies (including ONE North East).
We interact with local patient groups and promote public engagement in Science through fund raising and educational events (eg NESRF, mini Medical School), Science Media Centre Science Road Show, VITAE)
Further information about this area of research can be found at the Institute of Cellular Medicine as well as individual PI pages below.
Enquiries should be directed to Prof NJ Reynolds, n.j.reynolds@ncl.ac.uk or tel 0191 222 5851.
Staff List
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Prof. Mark Birch-Machin
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Prof. Ann Daly
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Prof. Anne Dickinson
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Prof. Brian Diffey
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Prof. Peter Farr
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Dr Muz Haniffa
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Dr James Lloyd
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Dr Penny Lovat
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Dr Julia Reichelt
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Prof. Nicholas Reynolds
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Dr Sophie Weatherhead
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Prof. Faith Williams
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Key Recent Publications
- Flockhart RJ, Armstrong JL, Reynolds NJ, Lovat PE. NFAT signalling is a novel target of oncogenic BRAF in metastatic melanoma. Br J Cancer. 2009 Oct 20;101(8):1448-55. Epub 2009 Sep 1.
- Hill DS, Martin S, Armstrong JL, Flockhart R, Tonison JJ, Simpson DG, Birch-Machin MA, Redfern CP, Lovat PE. Combining the endoplasmic reticulum stress-inducing agents bortezomib and fenretinide as a novel therapeutic strategy for metastatic melanoma. Clin Cancer Res. 2009 Feb 15;15(4):1192-8.
- Haniffa M, Ginhoux F, Wang XN, Bigley V, Abel M, Dimmick I, Bullock S, Grisotto M, Booth T, Taub P, Hilkens C, Merad M, Collin M. Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation. J Exp Med. 2009 Feb 16;206(2):371-85. Epub 2009 Jan 26.
- Birket MJ, Passos JF, von Zglinicki T, Birch-Machin MA. The relationship between the aging- and photo-dependent T414G mitochondrial DNA mutation with cellular senescence and reactive oxygen species production in cultured skin fibroblasts.
J Invest Dermatol. 2009 Jun;129(6):1361-6. Epub 2008 Dec 4. - Flockhart RJ, Diffey BL, Farr PM, Lloyd J, Reynolds NJ.
NFAT regulates induction of COX-2 and apoptosis of keratinocytes in response to ultraviolet radiation exposure. FASEB J. 2008 Dec;22(12):4218-27. Epub 2008 Aug 15 - Lovat PE, Corazzari M, Armstrong JL, Martin S, Pagliarini V, Hill D, Brown AM, Piacentini M, Birch-Machin MA, Redfern CP. Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress. Cancer Res. 2008 Jul 1;68(13):5363-9.
- Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, Wilson IJ, Burn J, Reynolds NJ, McLean WH, Cordell HJ. Filaggrin null mutations and childhood atopic eczema: a population-based case-control study. J Allergy Clin Immunol. 2008 Apr;121(4):940-46.e3. Epub 2008 Mar 4.
- Diffey BL. A behavioural model for estimating personal exposure to solar ultraviolet radiation. Photochem Photobiol 2008; 84: 371–375
- Ahmed S, Passos JF, Birket MJ, Beckmann T, Brings S, Peters H, Birch-Machin MA, von Zglinicki T, Saretzki G. Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress. J Cell Sci. 2008 Apr 1;121(Pt 7):1046-53. Epub 2008 Mar 11.
- Reichelt J. Mechanotransduction of keratinocytes in culture and in the epidermis.
Eur J Cell Biol. 2007 Dec;86(11-12):807-16. Epub 2007 Jul 25. Review. - Kirke SM, Lowder S, Lloyd JJ, Diffey BL, Matthews JN, Farr PM. A randomized comparison of selective broadband UVB and narrowband UVB in the treatment of psoriasis. J Invest Dermatol. 2007 Jul;127(7):1641-6. Epub 2007 Mar 22.
- Haniffa MA, Wang XN, Holtick U, Rae M, Isaacs JD, Dickinson AM, Hilkens CM, Collin MP.
Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J Immunol. 2007 Aug 1;179(3):1595-604. - Birket MJ, Birch-Machin MA. Ultraviolet radiation exposure accelerates the accumulation of the aging-dependent T414G mitochondrial DNA mutation in human skin.
Aging Cell. 2007 Aug;6(4):557-64. Epub 2007 Jun 18.
Lovat PE, Corazzari M, Armstrong JL, Fimia GM, Hill DS, Birch-Machin M, Redfern CP, Piacentini M. Targeting homeostatic mechanisms of endoplasmic reticulum stress to increase susceptibility of cancer cells to fenretinide-induced apoptosis: the role of stress proteins ERdj5 and ERp57. Br J Cancer. 2007 Apr 10;96(7):1062-71. Epub 2007 Mar 13.
Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial.
Lancet. 2006 Mar 11;367(9513):839-46. - McGill A, Frank A, Emmett N, Turnbull DM, Birch-Machin MA, Reynolds NJ. The anti-psoriatic drug anthralin accumulates in keratinocyte mitochondria, dissipates mitochondrial membrane potential, and induces apoptosis through a pathway dependent on respiratory competent mitochondria. FASEB J. 2005 Jun;19(8):1012-4. Epub 2005 Mar 31.
- Reichelt J, Furstenberger G, Magin TM. Loss of keratin 10 leads to mitogen-activated protein kinase (MAPK) activation, increased keratinocyte turnover, and decreased tumor formation in mice. J Invest Dermatol. 2004 Nov;123(5):973-81.
- Lovat PE, Di Sano F, Corazzari M, Fazi B, Donnorso RP, Pearson AD, Hall AG, Redfern CP, Piacentini M. Gangliosides link the acidic sphingomyelinase-mediated induction of ceramide to 12-lipoxygenase-dependent apoptosis of neuroblastoma in response to fenretinide. J Natl Cancer Inst. 2004 Sep 1;96(17):1288-99.
