Synopsis

Melanin synthesis in the human epidermis and hair follicle occurs within melanocyte-specific organelles called melanosomes that are transferred when (relatively) mature to adjacent keratinocytes. Melanin-accepting keratinocytes are distributed in the basal layer (S. basale) of the epidermis, as well as in the anagen hair follicle bulb. In the latter melanin is specifically donated to keratinocytes that will form the bulky cortex of the hair fiber. Only in epidermis is the process of melanogenesis continuous and UVR-protective. By contrast, in the hair follicle this process is tightly coupled to the hair growth cycle and occurs deep in the scalp beyond direct UVR influence.

While hypopigmentary/ hyperpigmentary disorders are not usually of medical consequence, there remains considerable clinical unmet need. Prominent examples for skin pigmentation include;  vitiligo, melasma, solar lentigines etc., while for the hair include aging-related graying or canities, poliosis etc.

The tonal palette of skin and hair colour that is detectable at the skin or hair surface is the product of a complex interplay of multiple biological events, each with their own regulatory control.  While significant progress has been made in our understanding of the phylogenetically-ancient process that is melanin synthesis at cell/molecular biological and biochemical levels, clinical interventions that can consistently and successfully treat pigmentary disorders, be they pathological or physiological (e.g., aging-related), have largely failed to translate from the laboratory to the clinic or salon. Much of this lack of progress must, in my view, be due to poor translatability of mouse studies to humans or to a failure to fully appreciate the often very significant artefacts of conventional cell/tissue and culture technologies and models.

This presentation will attempt to tease out the gaps in our current understanding of how skin and hair pigmentation is regulated in humans and will focus on how exploitation of this incomplete knowledge is being limited by deficiencies in our laboratory models.