Molecular pathways for skin formation

Michael Cangkrama, who has recently
completed his PhD on skin formation

The skin is the body’s largest organ. It forms in utero and is maintained throughout adult life. However, the womb is a more stable and regulated place than the more complex terrestrial environment, and skin function in an embryo and an adult is very different.

What are the molecular mechanisms contributing to the development, regulation and maintenance of the skin structure in utero and post-natally? Why are they different? It comes down to highly conserved genes, largely unchanged from fruit fly to human. These three genes (in mammals) are members of a family of transcription factors known as the Grainy head-like (Grhl) transcription factors that play a role in organ (including skin) development and barrier repair after tissue damage. Grhl1 and 3 are both highly expressed in skin.


Mr Michael Cangkrama is a doctoral student supervised by Professor Stephen Jane who heads the Epidermal Development Laboratory in the Department of Medicine. Michael’s research has focused on the Grhl transcription factor genes in skin barrier function.

Epidermal skin cells have a thirty day turnover, half the speed of the mucus membrane of the skin internal to the mouth, nasal passages and oesophagus. The research group identified the unique and cooperative roles of Grhl1 and Grhl3 that were both involved in the maintenance of the epidermal skin barrier through the regulation of their specific target genes, the transglutaminases. They characterized the molecular pathways driving the maintenance of the adult skin barrier using novel approaches, including systems biology, genetic screens, bioinformatics and phylogenetic approaches in silico to predict target genes and signaling networks that are conserved in mice and humans.

Understanding the mechanism of gene regulation by Grhl factors and their target genes will not only help tease out the evolutionarily conserved mechanisms of skin cell formation and maintenance, but it will throw light on the processes involved in human skin diseases such as atopic dermatitis and psoriasis.

In 2014 Michael won a Young Scientist Skin Research Travel Fellowship to present his work at an international conference, where he made both oral and poster presentations on "Coordinate function of the Grainyhead-like transcription factors is critical for maintenance of skin barrier function post-natally". His work has been published in four high impact factor journals comprising one review article and three research articles. A further research article has been submitted for review. He has submitted his thesis in early 2015 and has a postdoctoral position lined up in Switzerland.

Link: www.med.monash.edu.au/medicine/alfred/research/