Identification of Novel Therapeutic Targets to Inhibit Melanoma Metastasis

Overview

Topic status: We're looking for students to study this topic.

Australia has the world's highest incidence of melanoma with more than 1200 people
dying annually from this malignancy. While there has been considerable improvement in the early diagnosis and systemic therapies for patients with melanoma, the mortality rate of patients diagnosed with melanoma remain high primarily due to the metastatic dissemination of malignant cells to distant organs of the body. Understanding the mechanisms that promote the metastatic behaviour of malignant melanoma cells will lead to improved disease management for patients with melanoma. During malignant progression melanoma cells rely on the support of exogenous growth factors, such as Insulin-like growth factor-I (IGF-I) for their growth, survival and invasion into neighbouring tissues. While it has been demonstrated that IGF-I is a critical factor required for the survival, growth and motility of melanoma cells, little is known of the mechanisms underlying the downstream role of IGF-I in melanoma cell biology. Therefore, this project will provide the first comprehensive study into the critical downstream effectors of the IGF signalling pathway in melanoma progression, which will then be used as novel therapeutic targets to inhibit the spread of malignant melanoma cells. This study will also be the first in Australia to use the ex vivo 3D human skin equivalent (HSE) to model the early stages of melanoma metastasis in an effort to more accurately recapitulate the complex nature of the in vivo human skin environment.

Hypothesis: The hypothesis of this study is that critical downstream effectors of IGF-I
signalling can be used as therapeutic targets to inhibit the progression and metastasis of malignant melanoma. Therefore, the objective of the proposed project will be to
identify critical downstream mediators of activated IGF signalling that contribute to the
growth and invasion of malignant melanoma.

Aim 1: Develop and characterise the HSE as an ex vivo model for investigating the
mechanisms underlying malignant melanoma invasion by activated IGF signalling;

Aim 2: Identify critical downstream targets of activated IGF signalling using whole
genome microarrays; and

Aim 3: Validate the functional role of identified target genes in IGF-I stimulated
melanoma invasion using lentiviral-mediated delivery of gene specific shRNAs

Methods and techniques that will be developed in the course of this project:

  • Primary cell culture and development of the ex vivo HSE
  • Western blotting, qRT-PCR and Immunohistochemistry
  • Transcriptome analysis using gene expression microarrays
  • Lenti-viral mediated shRNA gene knockdown
  • FACS analysis and isolation of cell populations
Study level
PhD, Honours
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Cell and Molecular Biosciences

Contact
Please contact the supervisor.