Research Interests

I have contributed to the field of skin research for 30 years. I was a founder member of the Scottish Skin Biology Club, of which I was chairman 1995-2000. Significant past contributions have included:

• the elucidation of the biosynthetic pathways for activation of adrenal and gonadal steroid hormones in human skin.
• the location of steroid hormone target cells in the epidermis, dermis and epidermal appendages: androgen receptors in the hair follicle.
• molecular mechanisms of androgen resistance syndromes.

Over the past decade, my research interests have become centred on the role of gap junctional intercellular communication in skin.

Research themes

Gap junctional intercellular communication in skin development and disease; Skin Cancer ; Genetic basis of Skin disorders.

Current Research

Over the past decade, my research interests have become centred on the role of gap junctional intercellular communication in skin.
Significant contributions in this field have included:

• the discovery of gap -junctional communcation compartments in the hair follicle
• elucidation of the changing patterns of gap junctional intercellular commuincation and connexin protein distribution during embryonic skin development
• elucidation of changes in connexin distribution in relation to epidermal cell proliferation (after wounding, in psoriasis and in skin cancer)
• connexin mutations in palmoplantar keratodermas
• production of transgenic mouse models to study connexin functions in skin by expressing connexin mutants targeted to epidermal keratinocytes.  

Gap Junctions and Connexins - a summary

Intercellular communcation via gap junctions is probably present in tissues of most, if not all multicellular animals. It is postulated that this form of cell-cell communication, involving direct exchange of small metabolites and ions, is required to co-ordinate cell behaviour and maintain homoeostasis. In the vertebrates, gap junctions are formed from connexins (a family of at least 13 closely related membrane proteins in mouse and man). A worldwide community of connexin researchers has grown up (to join send e-mail 'join connexin connection' to: majordomo@listserve.uni-stuttgart.de )

However, in spite of impressive advances in our understanding of the structural basis of gap junctions and of the properties of connexins, important basic issues remain unresolved. These include: the significance of gap junctional communication for cellular metabolism, survival, proliferation and differentiation; the significance of multiple connexins within cells for the properties of their gap junctions; the mechanisms which control synthesis, trafficking and gating of gap junctions; whether or not connexins have functions additional to their roles in gap junctions.

The skin is an ideal system in which to explore some of these fundamental problems at the level of an intact organ or cell cultures, because of the multiplicity of expressed connexins, the changing patterns of gap junctional intercellular communication and connexin expression during development. Combined with well established technologies for tissue specific transgenesis in epidermis and hair follicles this makes skin a system of choice for applying the newest functional-genetic approaches to study integrative physiology of gap junctions and connexins.

It has long been suspected that changes in distribution or properties of gap junctions play an important role in carcinogenesis. Again, skin cancers provide a unique opportunity to research this aspect of neoplasia, both through descriptive studies of human skin tumours and experimental skin carcinogenesis in mouse.

Most recently, several important genetic disorders caused by connexin gene mutations have been discovered [link to OMIM]. These include a peripheral neuropathy (X-linked Charcot -Marie- Tooth disease), sensorineural deafness (DFNA , DFNB), two forms of congenital cataract and at least three skin disorders. These last form a major focus of our current research.

Our current gap junction research

• Transgenic mouse models expressing dominantly acting mutant connexins in epidermis using keratin promoters: the roles of connexin 26 (gjb2) and closely related connexins in gap junctional intercellular communication during skin and hair follicle development.
• Roles of connexins in disorders of keratinization: physiology and immunopathology of connexin gene mutations affecting skin.
• Expression and trafficking of connexins during tumourigenesis: organotypic models for the study of keratinocyte differentiation and neoplasia.

1. Kam E, Hodgins MB 1992 Communication compartments in hair follicles and their implication in differentiative control. Development 114: 389-393.
   Abstract
2. Choudhry R, Pitts JD, Hodgins MB. 1997 Changing patterns of gap junctional intercellular communication and connexin distribution in mouse epidermis and hair follicle during embryonic development. Dev Dynam 210: 417-430.
   Abstract
3. Lucke T, Choudhry R, Thom R, Selmer I-S, Burden AD, Hodgins MB 1999 Up-regulation of connexin-26 is a feature of keratinocyte differentiation in hyperproliferative epidermis, vaginal epithelium and buccal epithelium. J Invest Dermatol. 112: 101-108.
   Abstract
4. Hodgins MB, Munro CS, Shore L, et al. 1999 The skin phenotypes of dominant connexin 26 mutations. J. Invest Dermatol 113 (3): 083.
5. Lucke T, Choo D, Hodgins MB 1999 Distribution of connexins 26 and 43 in basal cell carcinoma, epidermal squamous cell carcinoma and precursor lesions. J Invest Dermatol 113 (3): 201.
6. Choudhry R, Shore L, Brown K, et al. 2000 Disrupting gap junction proteins in epidermis: Mice expressing mutant connexin 26 from a keratin promoter J Invest Dermatol 115 (3): 536.
7. Kelsell D, Dunlop J, Hodgins MB (2001) Human diseases: clues to cracking the connexin code. Trends in Cell Biology 11(1) 2-6. in press.
   Abstract
8. Rouan F, White TW, Brown N, Taylor AM, Lucke TW, Paul DL, Munro CS, Uitto J, Hodgins MB, and Richard G. 2001. Trans-dominant inhibition of connexin-43 by mutant connexin-26: implications for dominant connexin disorders affecting epidermal differentiation J Cell Sci 2001 114: 2105-2113.
9. Shore L, McLean P, Gilmour SK, Hodgins MB, and Finbow ME (2001) Polyamines regulate gap junction communication in connexin 43-expressing cells. Biochemical Journal (2001) 357, 489–495.
   Abstract
10. George Bakirtzis, Rukhsana Choudhry, Trond Aasen, Leonard Shore, Ken Brown, Sheila Bryson, Stephen Forrow, Laurence Tetley, Malcolm Finbow, David Greenhalgh and Malcolm Hodgins.
    Targeted epidermal expression of mutant Connexin 26(D66H) mimics true Vohwinkel syndrome and provides a model for the pathogenesis of dominant connexin disorders.
    Human Molecular Genetics, 2003, Vol. 12, No. 14 1737-1744
    Abstract
    Full Text
11. Aasen T, Hodgins MB, Edward M, Graham SV.
    The relationship between connexins, gap junctions, tissue architecture and tumour invasion, as studied in a novel in vitro model of HPV-16-associated cervical cancer progression.
    Oncogene. 2003 Sep 11;22(39):6025-36.
    Abstract
12. Thomas T, Aasen T, Hodgins M, Laird DW. 2003.
    Transport and function of cx26 mutants involved in skin and deafness disorders.
    Cell Commun Adhes. 10(4-6):353-8.
    Abstract
13. Bakirtzis G, Jamieson S, Aasen T, Bryson S, Forrow S, Tetley L, Finbow M, Greenhalgh D, Hodgins M. 2003.
    The effects of a mutant connexin 26 on epidermal differentiation.
    Cell Commun Adhes. 10(4-6):359-64.
    Abstract
14. Hodgins MB. 2004.
    Connecting wounds with connexins.
    J Invest Dermatol. 122(5):IX-X
    Abstract
15. Tavadia, S., Authi, K.S., Hodgins, M.B. & Munro, C.S. 2004.
    Expression of the sarco/endoplasmic reticulum calcium ATPase type 2 and 3 isoforms in normal skin and Darier's disease.
    British Journal of Dermatology 151 (2), 440-445.
    Abstract  

Dermatology
School of Medicine
College of Medical, Veterinary and Life Sciences
Robertson Building
Glasgow University
56 Dumbarton Road
G11 6NU
tel: +44 (0)141 330 4006
fax: +44 (0)141 330 4008
Malcolm.Hodgins@glasgow.ac.uk

Funding

• BBSRC
• University of Glasgow
• Scottish Enterprise
• Industry

Collaborators

• Dr. G. Bakirtzis
• Prof. ME Finbow
• Dr. DA Greenhalgh
• Dr. S. Forrow
• Dr. L. Tetley
• Dr. M.Edward
• Dr. SV Graham
• Mr. T. Aasen
• Ms. E. Kandyba
• Dr. A Reith
• Professor CS Munro
• Dr. G Richard (T. Jefferson University, Philadelphia, Pa.)
• Dr. D. Kelsell