Professor Julie Thornton,

Professor in Cutaneous Biology

Research

The skin provides an excellent accessible human cell and tissue model with an exceptional ability for regeneration that significantly declines with age. Along with its appendages (e.g. glands, hair follicles) it is a complex organ, which is continually self-renewing and remodelling. The hair follicle recapitulates embryogenesis throughout adult life with each hair cycle displaying a unique postnatal regenerative capacity.Cell types of different lineages, e.g. epithelial, connective, vascular, epithelial stem cells, mesenchymal stem cells, melanocytes, can all be isolated and cultured either individually or in 3D-co-culture, thus providing an excellent collection of primary human cells for cellular and molecular studies of cell signaling, changes in gene and protein expression, including epigenetic changes and the regulation of gene regulatory networks.Using these human cell and tissue models my research is focused primarily on wound healing and ageing, particularly in post-menopausal women.

There is a strong need to develop relevant human cell and tissue models to decipher the underpinning mechanisms of disease, which will be key to providing effective therapeutics and in identifying those patients at risk of developing particular diseases. Since it is possible to obtain both normal and diseased human skin from different age groups, and different populations, and the different types of primary cells, including stem cells, can be isolated and cultured, this opens up an extensive range of potential areas for investigation. Since primary cells in isolation may not respond in the same way as they would in their normal environment, we are developing 3D co-cultures, and 3D-cultures using scaffolds. Using bioimaging we can compare the spatial arrangement of these cells with ex vivo whole tissue to identify superior, relevant in vitro models for human studies.

Current PhD Students

Lucy Trevor:

Influence of adipocytes on radiotherapy tissue; implications on wound-healing and scar tissue formation/maturation

Rachael Sutherland-Sedman:

Aging of the hair follicle dermal environment

Paul Norton:

Effective removal of antimicrobial resistant bacteria from chronic wounds

Aqib Ahmed:

Role of TET enzymes in hair growth regulation

Aaiad Al Rikabi:

Impaired wounded healing and inflammation: the role of the dermal fibroblast

Other Research Projects and Collaborations with Industry:

KTP Innovate UK funded collaboration with Jacobo Elies (School of Pharmacy and Medical Sciences) and Alex Chapman (Labskin, York). This is principally to apply our expertise in human skin primary cell culture to Labskin’s current 2-cell skin equivalent model to produce a superior 3-cell pigmented model.

Aveda/Estee Lauder

We have been working with this company for several years to understand more about the biology of ageing hair.

Nutraceutical Wellness LLC (Nutrafol) a NY-based nutritional supplement company that aims to help men and women experiencing thinning hair through a multi-targeted approach are collaborating on a project that bring together science and expertise to research human hair biology, hair thinning, and the connection between molecular mechanisms and hormonal signals in many cell types.

Follicum AB, (www.follicum.com) a biotech company are working with us to understand the mechanism of their drugs on hair loss and diabetes.

PUBLICATIONS

INVITED REVIEWS:

Thornton MJ (2013) Estrogens and Aging Skin. Dermato-Endocrinology. 5: 264-270

Stevenson S and Thornton MJ (2007) Effect of estrogens on skin aging and the potential role of SERMs. Clinical Interventions in Aging 2: 283-297

Zouboulis CC, Chen WC, Thornton MJ, Qin K, Rosenfield R (2007) Sexual hormones in human skin. Horm Metab Res 39: 85-95

Thornton MJ (2005) Oestrogen functions in skin and skin appendages. Expert Opin. Ther. Targets 9: 617-629

Thornton, MJ, (2002) The biological actions of oestrogens on skin. Exp Dermatol. 11: 487-502

INVITED EDITORIALS

Thornton MJ (2016) Human skin: a mirror for estrogen action? The Journal of The North American Menopause Society; 23: 119-120

PEER-REVIEWED PAPERS

Castellano-Pellicena I, Uzunbajakava NE, Mignon C, Raafs B, Botchkarev VA and Thornton MJ (2019) Does Blue Light Restore Human Epidermal Barrier Function via Activation of Opsin During Cutaneous Wound Healing? Lasers in Surgery and Medicine 51: 370-382

Pomari E, Dalla Valle L, Pertile P, Colombo L and Thornton MJ (2015) Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts. FASEB J. 29: 508-524

Stevenson S, Sharpe DT and Thornton MJ (2009) Effects of oestrogen agonists on human dermal fibroblasts in an in vitro wounding assay. Exp Dermatol. 18: 988-990

Salem MM, Shalbaf M, Gibbons NC, Chavan B, Thornton MJ and Schallreuter KU (2009) Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage. FASEB J. 23: 3790-3807

Wood JM, Decker H, Hartmann H, Chavan B, Rokos H, Spencer JD, Hasse S, Thornton MJ, Shalbaf M, Paus R and Schallreuter KU (2009) Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. FASEB J. 23: 2065-2075

Stevenson S, Taylor AH, Meskiri A, Sharpe DT and Thornton MJ (2008) Differing responses of human follicular and non-follicular scalp cells in an in vitro wound healing assay: effects of estrogen on vascular endothelial growth factor secretion. Wound Repair Regen. 16: 243-253

Stevenson S, Nelson LD, Sharpe DT and Thornton MJ (2008) 17beta-estradiol regulates the secretion of TGF-beta by cultured human dermal fibroblasts. J Biomater Sci Polym Ed; 19: 1097-1109

Thornton MJ, Nelson LD, Taylor AH, Laing I and Messenger AG (2006) The modulation of aromatase and estrogen receptor alpha (ER) in cultured human scalp dermal papilla cells by dexamethsone: a novel mechanism for selective action of estrogen via estrogen receptor beta (ER)? J Invest Dermatol 126: 2010-2018

Davies GC, Thornton MJ, Jenner TJ, Chen YJ, Hansen JB, Carr RD and Randall VA (2005) Novel and established potassium channel openers stimulate hair growth in vitro: implications for their modes of action in hair follicles. J Invest Dermatol 124: 686-694

Thornton, MJ, Taylor, AH, Mulligan, K and Al-Azzawi F, Lyon C, O'Driscoll J and Messenger AG (2003) Oestrogen receptor beta (ERb) is the predominant oestrogen receptor in human scalp skin. Exp Dermatol 12: 181-190

Thornton, MJ, Taylor, AH, Mulligan, K and Al-Azzawi F, Lyon C, O'Driscoll J and Messenger AG (2003) The distribution of estrogen receptor beta (ERbeta) is distinct to that of ERalpha and the androgen receptor in human skin and the pilosebaceous unit. J Investig Dermatol Symp Proc 8: 100-103

Thornton MJ, Hibberts NA, Street T, Brinklow BR, Loudon AS and Randall VA (2001) Androgen receptors are only present in mesenchyme-derived dermal papilla cells of red deer (Cervus elaphus) neck follicles when raised androgens induce a mane in the breeding season. J Endocrinol. 168: 401-408

Randall VA, Hibberts NA, Thornton MJ, Merrick AE, Hamada K, Kato S, Jenner TJ, de Oliveira I and Messenger AG (2001) Do androgens influence hair growth by altering the paracrine factors secreted by dermal papilla cells? Eur J Dermatol. 11: 315-320

Randall VA, Hibberts NA, Thornton MJ, Hamada K, Merrick AE, Kato S, Jenner TJ, De Oliveira I and Messenger AG (2000) The hair follicle: a paradoxical androgen target organ. Horm Res. 54: 243-250

Thornton, MJ, Taylor, AH, Mulligan, K and Al-Azzawi F (2000) Oestrogen receptor beta is not present in the pilosebaceous unit of red deer skin during the non-breeding season. Horm Res. 54: 259-262

Thornton, MJ, Hamada, K, Messenger, AG and Randall, VA (1998) Androgen-dependent beard dermal papilla cells secrete autocrine growth factor(s) in response to testosterone unlike scalp cells. Journal of Investigative Dermatology. 111: 727-732

Hamada, K, Thornton, MJ, Laing, I, Messenger, AG and Randall, V A (1996) The metabolism of testosterone by dermal papilla cells cultured from human pubic and axillary follicles concurs with hair growth in 5-reductase deficiency. Journal of Investigative Dermatology.106: 1017-1022

Thornton, MJ, Brinklow, BR, Loudon, ASI and Randall, VA (1996) The ability to culture dermal papilla cells from red deer (Cervus elaphus) hair follicles with differing hormonal responses in vivo offers a new model for studying the control of hair follicle biology. Journal of Experimental Zoology. 275: 452-458

Randall, VA, Thornton, MJ, Hamada, K and Messenger, AG (1994) Androgen action in cultured dermal papilla cells from human hair follicles. Skin Pharmacology. 7: 20-26

Thornton, MJ, Laing, I, Hamada, K, Messenger, AG and Randall, VA (1993) Differences in testosterone metabolism in beard and scalp hair follicle dermal papilla cells. Clinical Endocrinology. 39: 633-639

Randall, VA, Thornton, MJ, Messenger, AG, Hibberts, NA, Loudon, ASI and Brinklow, BR (1993) Hormones and hair growth: variations in androgen receptor content of dermal papilla cells cultured from human and red deer (Cervus elaphus) hair follicles. Journal of Investigative Dermatology. 101: 114S-120S

Randall, VA, Thornton, MJ, and Messenger, AG (1992) Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp. Journal of Endocrinology. 133: 141-147

Randall, VA, Thornton, MJ, Hamada, K and Messenger, AG (1992) The mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo. Journal of Investigative Dermatology. 98: 86-91

Thornton, MJ, Messenger, AG, Elliott, K and Randall, VA (1991) The effect of androgens on the growth of cultured dermal papilla cells derived from beard and scalp hair follicles. Journal of Investigative Dermatology. 97, 345-348 (high impact paper)

Randall, VA, Thornton, MJ, Hamada, K, Redfern CPF, Nutbrown, M, Ebling, FJG and Messenger, AG (1991) Androgens and the hair follicle: cultured human dermal papilla cells as a model system. Annals of New York Academy of Sciences. 642: 355-375

Hull, SM, Nutbrown, M, Pepall, L, Thornton, MJ, Randall, VA and Cunliffe, WJ (1991) Immunohistological and ultrastructure comparison of the dermal papilla and hair follicle bulb from 'active' and 'normal' areas of alopecia areata. Journal of Investigative Dermatology. 96: 673-681

Hull, SM, Nutbrown, M, Thornton, MJ, Cunliffe, WJ and Randall, VA (1991) Evidence for a subclinical state of alopecia areata. Annals of New York Academy of Sciences. 642: 478-479

Nutbrown, M, Hull, SM, Thornton, MJ, Cunliffe, WJ and Randall, VA (1991) The ultrastructure of the dermal papilla-epithelial junction in normal and alopecia areata hair follicles. Annals of New York Academy of Sciences 642: 476-477

Thornton, MJ, Laing, I, Hamada, K, Messenger, AG and Randall, VA (1991) Metabolism of testosterone by cultured dermal papilla cells from human beard, pubic, and scalp hair follicles. Annals of New York Academy of Sciences. 642: 452-453

Randall, VA, Thornton, MJ, and Redfern CPF (1991) Dermal papilla cells from human hair follicles express mRNA for retinoic acid receptors in culture Annals of New York Academy of Sciences 642: 457-458

BOOK CHAPTERS

Laing I &Thornton J (2017)Reproductive Endocrinology. In: Clinical Biochemistry, Editor N Ahmed, Oxford University Press, (2nd edition)

Laing I &Thornton J (2011)Reproductive Endocrinology. In: Clinical Biochemistry, Editor N Ahmed, Oxford University Press, pp 415-449

Thornton MJ, Nelson LD, Taylor AH, Mulligan KT, Al-Azzawi F and Messenger AG (2003) Human Non-Balding Scalp Dermal Papilla Cells Express Estrogen Receptor beta (ERb) Protein in vivoand in vitro. In: Hair Science and Technology, Editor D. Van Neste pp105-112 (80%,7 pages) ·

Thornton, MJ, Thomas, DG, Jenner, TJ, Brinklow, BR, Loudon, ASI and Randall, VA (1996) Testosterone or IGF-1 stimulated hair growth in whole organ culture only in androgen-dependent red deer hair follicles. In: Hair research in the next Millenium. Proceedings of the 1st Tricontinental Meeting of Hair Research Societies, Brussels, 1995. Springer-Verlag. Editors D van Neste & VA Randall

Thornton MJ, Thomas DG, Brinklow BR, Louden ASI and Randall VA (1994) Breeding mane hair follicles from red deer (Cervus elaphus) stags are stimulated by testosterone in whole organ culture. In: Recent Developments in Deer Biology, Editor JA Milne

Research supervision

Professor Julie Thornton is responsible for the supervision of 2 postgraduate researchers at the University of Bradford.