Prof Lindeman's laboratory, co-headed with Dr Visvader, has played an influential role in the identification of mammary stem and progenitor cells, elucidation of the mammary epithelial cell hierarchy and gaining insights into how female hormones regulate mammary gland development and cancer. In parallel, I have established translational research platforms such as patient-derived tumour xenograft (PDX) models, which offer powerful preclinical models to test new drugs.
I am a clinician-scientist engaged in basic, translational and clinical breast cancer research, with the long-term goal to identify and exploit novel cancer targets to improve patient outcomes. My research, which covers both sporadic and hereditary forms of breast cancer, is focussed on elucidating the breast epithelial cell hierarchy, in order to identify key regulators responsible for breast epithelial cell proliferation, differentiation and cancer.
I am a cellular biologist studying lineage commitment and differentiation in the mammary gland. Key interests include defining transcriptional regulators that are important for mammary gland development and oncogenesis, and the characterisation of stem cells and other epithelial cell types in breast tissue.
Genetic Variants, Phenotypic Spectrum And Breast Cancer Risk Associated With Germline Mutations In PALB2: Identifying Female PALB2 Mutation Carriers At The Time Of Diagnosis
Funder
National Health and Medical Research Council
Funding Amount
$45,093.00
Summary
Population studies of female breast cancer (BC) show only a small proportion of familial aspects of BC can be explained by current knowledge of its causes. Women carrying PALB2 mutations who also have a strong family history of BC are of increased risk of BC. Our work will further define the risks and devise criteria to identify women most likely to carry PALB2 mutations. This will help prioritize testing, classify PALB2 variants and provide appropriate clinical management to carriers.
A Randomised Trial Of A Decision Aid For Women At Increased Risk For Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$115,110.00
Summary
Epithelial ovarian cancer is the leading cause of death from gynaecological malignancy in Australia. The majority of women with ovarian cancer are diagnosed with advanced disease, and the chance of cure is low. The strongest risk factor for ovarian cancer identified to date is a family history of ovarian cancer, and up to 5% of all ovarian cancers are thought to be due to dominantly inherited mutations in a small number of ovarian-cancer-related genes. National guidelines on surveillance and pro ....Epithelial ovarian cancer is the leading cause of death from gynaecological malignancy in Australia. The majority of women with ovarian cancer are diagnosed with advanced disease, and the chance of cure is low. The strongest risk factor for ovarian cancer identified to date is a family history of ovarian cancer, and up to 5% of all ovarian cancers are thought to be due to dominantly inherited mutations in a small number of ovarian-cancer-related genes. National guidelines on surveillance and prophylactic strategies have recently been ratified. These are largely based on expert opinion. Because of the uncertain efficacy of ovarian cancer screening and the high mortality associated with ovarian cancer, prophylactic oophorectomy is considered an option for women at high risk. Decisions about optimal care are difficult for both women and their doctors. Efforts to improve services for women who are trying to make informed decisions about screening and prophylactic strategies under conditions of uncertainty must be informed by sound knowledge of the efficacy of educational interventions. Decision aids have been developed as adjuncts to practitioners' counselling to prepare patients for decision-making. The proposed randomised controlled trial will compare the efficacy of a general educational pamphlet and that of a tailored decision aid. A total of 120 women at risk for ovarian cancer who are attending one of five familial cancer clinics will be included in the trial to determine the efficacy of different educational interventions in preparing women for decision-making about screening and prophylactic options.Read moreRead less
Integration Of Genetic Testing For Risk Associated Genomic Variants And Rare Predisposition Genes Into The Management Of High Risk Hereditary Breast Cancer Families
Funder
National Health and Medical Research Council
Funding Amount
$645,457.00
Summary
Breast Cancer is a common disease with up to 20% of cases associated with a family history. This project aims to assess the contribution of recently identified risk associated genomic variants and rare predisposition genes to the heritability of familial breast cancer. The project will also assess the experience of clinicians and patients as we aim to use this information to help improve the process of risk assessment and genetic counselling in the specialist Familial Cancer Centres.
Mapping And Identification Of Novel Breast Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$354,419.00
Summary
Breast cancer is one of Australia?s major cancer problems, but we still do not fully understand why certain people are at higher risk of the disease than others. In recent years two genes have been shown to be abnormal in a small number of people with strong family history of breast cancer and-or ovarian cancer. This study will search for the identity of other genes of this kind. It will take advantage of a large network of researchers which has been working to recruit women with a strong family ....Breast cancer is one of Australia?s major cancer problems, but we still do not fully understand why certain people are at higher risk of the disease than others. In recent years two genes have been shown to be abnormal in a small number of people with strong family history of breast cancer and-or ovarian cancer. This study will search for the identity of other genes of this kind. It will take advantage of a large network of researchers which has been working to recruit women with a strong family history of breast cancer from around Australia over the last two years. In this short time such large numbers of women have come forward that a study of this kind will be among the largest in the world. The results of this research, in terms of location of possible new genes causing high risk of breast cancer, will be shared with other researchers in Europe and the US who are working toward the same goals. This will ensure that progress is as rapid as possible. Based on experience with the two previously discovered breast cancer genes, this research will also shed light on the types of changes that drive the malignancy of breast cancer cells. It will have implications for improved prevention, diagnosis and treatment of breast cancer.Read moreRead less
Regulation And Assembly Of Nuclear DNA Repair Centres
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Genetic defects in DNA repair genes are associated with increased cancer risk in humans. For example, BRCA1 and BRCA2 gene mutations are the most common causes of familial breast cancer, and MLH1 gene mutations are the most common cause of familial non-polyposis colorectal cancer. We have identified a novel human DNA repair protein termed ASCIZ that performs a similar function to BRCA1 and BRCA2 in that it regulates the concentration of the RAD51 repair protein in specific DNA repair centres in ....Genetic defects in DNA repair genes are associated with increased cancer risk in humans. For example, BRCA1 and BRCA2 gene mutations are the most common causes of familial breast cancer, and MLH1 gene mutations are the most common cause of familial non-polyposis colorectal cancer. We have identified a novel human DNA repair protein termed ASCIZ that performs a similar function to BRCA1 and BRCA2 in that it regulates the concentration of the RAD51 repair protein in specific DNA repair centres in the cell nucleus. However, ASCIZ performs this function in response to different types of DNA damage than BRCA1-BRCA2, and it acts in concert with the MLH1 protein. Here we want to study how ASCIZ regulates the assembly of DNA repair centres, and if it does so with support by the BRCA1-BRCA2 proteins. We also want to know if DNA repair functions of the RAD51 protein are diminished when it is not located in repair centres, and we want to identify novel proteins involved in this process. Our preliminary data show that cells that lack ASCIZ become dramatically hypersensitive to DNA damaging agents that are similar to clinically used chemotherapy drugs. We hope that our studies may identify possible approaches to develop drugs against ASCIZ and related proteins in order to kill cancer cells more effectively.Read moreRead less
Risk Factors, Screening, Prophylaxis And Outcomes In Individuals From Breast Cancer Families: KConFab Follow-Up Study
Funder
National Health and Medical Research Council
Funding Amount
$510,675.00
Summary
Having a strong family history of breast cancer is one of the most important risk factors for the disease. Two major genes, BRCA1 and BRCA2, have been identified which, when abnormal, result in an inherited tendency towards developing breast cancer. Women with a strong family history of breast cancer can undergo testing for these gene abnormalities via Family Cancer Centres around Australia. However, once a gene abnormality is found, little is known about the best ways to prevent cancer or detec ....Having a strong family history of breast cancer is one of the most important risk factors for the disease. Two major genes, BRCA1 and BRCA2, have been identified which, when abnormal, result in an inherited tendency towards developing breast cancer. Women with a strong family history of breast cancer can undergo testing for these gene abnormalities via Family Cancer Centres around Australia. However, once a gene abnormality is found, little is known about the best ways to prevent cancer or detect it early. The Kathleen Cuningham Consortium for Research into Familial Aspects of Breast Cancer (kConFab) has been recruiting families with exceptionally strong histories of breast cancer since 1997. kConFab is funded to collect epidemiological information and biological specimens on such individuals only at the time of their initial recruitment. In 2000 the NHMRC recognised the importance of undertaking clinical follow-up of this precious cohort of individuals, and provided funding through a 3 year project grant to commence the first round of 3 yearly follow-up on this cohort (NHMRC Project Grant #145684). The first 2 years of this follow-up has been completed successfully and the current is application is for a renewal of funding (to commence in 2004) to enable us to undertake further follow-up of the now much larger cohort. In the short term we will examine the screening and preventive surgery behaviours of high risk women within this study to determine whether they are optimal. The ultimate aim of this long term follow-up of individuals in kConFab is to determine what factors impact on the development of cancer in well individuals with a genetic predisposition to breast cancer.Read moreRead less