2010 Annual Report - Institute for Molecular Bioscience - University ...

imb annual report 2010
36
RICK STURM
MELANOGENIX RESEARCH GROUP
THE MELANOGENIX (MELANOCYTE
biology and pigmentation genetics)
laboratory is studying the molecular,
genetic and cellular basis underlying
normal human variation in the pigmentary
traits of skin, hair and eye colour. Several
genome-wide association studies
(GWAS) for pigmentation have now been
conducted and identified SNP markers in
known (TYR, TYRP1, OCA2, SLC45A2,
SLC24A5, MC1R, ASIP, KITLG) and
previously unknown (SLC24A4, IRF4,
TPCN2) candidate genes. We have
investigated skin and hair colour genetic
associations in Europeans, and discovered
that responsible polymorphisms are found
within a range of pigmentation genes,
whereas blue-brown eye colour can be
explained by a single SNP proposed to
regulate OCA2 expression. There is a
strong genotype-by-age effect of IRF4 on
nevus count, and the responsible SNP is
associated with increased melanoma risk.
In addition, we have found that this SNP
can modulate the transcriptional expression
of the IRF4 gene in melanocytes.
Functional analysis of the human
pigmentation gene set will ultimately
provide a full appreciation of this biological
system linking genotype with phenotype.
Specifically the role of the MC1R gene
variants in directing skin phototype and
response to UV-induced ligand binding
and receptor activation is a major area
of investigation. In addition, the group
is studying the process of development
and differentiation of the melanocytic
cell lineage using primary melanoblast
and melanocyte cell culture, as well as
coculture of these cells with keratinocytes.
This will provide information to allow
the genes and processes involved
in melanoma tumour formation and
metastasis to be examined. Each of
these aims centres on the identification
and molecular characterisation of genes
involved in melanocyte cell function.
RESEARCH PROJECTS
• Understanding skin cancer risk
phenotypes through studying the
interaction of genes involved in skin,
hair and eye colour
• Molecular, genetic and cellular analysis
of melanin formation
• Analysis of MC1R genotyped human
melanocytes in monoculture and in
coculture with keratinocytes
• Melanoma spheres as a model for
melanoma development and metastasis
• Role of NR4A nuclear hormone
receptors in melanocytic cells
KEY PUBLICATIONS
Duffy, D.L. et al. (2010). IRF4 variants have
age-specific effects on nevus count and
predispose to melanoma. American Journal
of Human Genetics 87: 6-16.
Duffy, D.L., Zhao, Z.Z., Sturm, R.A.,
Hayward, N.K., Martin, N.G., and
Montgomery, G.W. (2010). Multiple
pigmentation gene polymorphisms
account for a substantial proportion of
risk of cutaneous malignant melanoma.
Journal of Investigative Dermatology 130:
520-528.
Johanson, H.C., Chen, W., Wicking,
C., and Sturm, R.A. (2010). Inheritance
of a Novel Mutated Allele of the OCA2
Gene Associated with High Incidence of
Oculocutaneous Albinism in a Polynesian
Community. Journal of Human Genetics
55: 103-111.
Sturm, R.A. (2009). Molecular genetics
of human pigmentation diversity. Human
Molecular Genetics 18: R9-R17.
Sturm, R.A., and Larsson, M. (2009).
Genetics of human iris colour and
patterns. Pigment Cell and Melanoma
Research 22: 544-562.
LAB MEMBERS
Research Officers: Dr Kimberley
Beaumont, Dr Aaron Smith, Dr Shu Shyan
Wong
Research Assistants: Garth Douglas,
Matthew Harrison, Kasturee Jagirdar,
Wen Lim, Darren Smit, Caroline Sturm
PhD Students: Stephen Ainger, Helene
Johanson
Honours Student: Amanda Ong
Visiting Students: Puya Gharahkhani
(PhD Vet Science), Elizabeth Webb (USA
Fulbright Scholar)
Human melanoma tumour.