Melanoma Genetics: Clinical Translation Of The Germline-somatic Continuum
Funder
National Health and Medical Research Council
Funding Amount
$2,231,372.00
Summary
While new targeted and immune therapies can improve prognosis from metastatic melanoma, long-term survival for most patients remains elusive due to drug resistance or failure of the immune system to kill the tumour. There thus remains a significant need to improve early detection, monitoring of relapse, and treatment strategies, to increase survival and provide cures. My research vision addresses these three pillars of cancer research using innovative and cutting edge genetic approaches.
Investigating Deregulation Of Mitosis As A Mechanism Of Tumourigenesis In MYCN-driven Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$372,298.00
Summary
Neuroblastoma chemotherapy often only works temporarily because a small number of tumour cells can resist drugs and eventually regrow as a new tumour. These resistant cells resemble the very first cells that turn into a cancer cell at tumour initiation. We have used single cell technology to uncover genetic markers of tumour initiating cells. In this project we will determine how these marker genes cause tumour initiation and develop therapies that target them in drug resistant neuroblastoma.
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.
Role Of Snail Proteins In Mediating Intestinal Stem Cell Identity
Funder
National Health and Medical Research Council
Funding Amount
$646,698.00
Summary
The lining of the intestine is constantly renewed by stem cells which also contribute to replenishment of this layer following damage caused by trauma, infection or treatments such as chemotherapy. We are studying how a family of gene regulators called Snail proteins act to maintain stem cells in the gut. Snail proteins have also been found to be present at high levels in bowel tumours so we are examining their role in the genesis of tumours and resistance to common treatments.
Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Functional Analysis Of Relapse Predictive Genes In Wilms Tumour
Funder
National Health and Medical Research Council
Funding Amount
$571,311.00
Summary
Wilms tumor is a paediatric kidney cancer, the most common abdominal tumour seen in children. About 20% of Wilms tumour patients have relapsing fatal tumours. We have found two genes that mark tumours which relapse: C-EBPB and CLK1. Characterization of C-EBPB and CLK1 will yield new information regarding the mechanisms underlying development and progression of Wilms tumours, leading to improved treatment for Wilms tumor patients. Both C-EBPB and CLK1 may also have roles in other human cancers.
Roles For Gastrin And Hypoxia In Colorectal Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$636,508.00
Summary
Our objective is to understand how hormones such as gastrin stimulate the development of colorectal cancer. Our preliminary data shows that the amount of gastrin produced by tumour cells is increased by low oxygen. We will therefore study how the increase in gastrin in response to low oxygen causes a compensatory growth of the tumour. The ability to interfere with this process should allow us to slow tumour growth.
Manipulating Oncogenic-signalling Pathways In The Genesis And Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$601,484.00
Summary
Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry is damaged in melanomas. This work will greatly accelerate the development of new therapi ....Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry is damaged in melanomas. This work will greatly accelerate the development of new therapies.Read moreRead less
Targeting The Interface Between Tumours And Their Microenvironment For The Treatment Of Gastrointestinal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$785,045.00
Summary
This fellowship explores the synergistic interactions between intestinal cancer cells and the tumour microenvironment and which promote survival, expansion, migration and invasion as well as facilitating the development of resistance to anti-cancer therapy. Aided by the clinical expertise of my collaborators, my efforts are likely to yield translational outcomes, including the development of therapeutic IL-11 antagonists, and of a serum protein signature indicative of early stage gastric cancer.