Identifying The Critical Pathways Which Regulate Vertebrate Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$552,131.00
Summary
Understanding the genes which underlie human birth defects is of immense clinical importance. Our laboratory is a world-leader investigating a gene responsible for facial skeleton development, Grhl2. With our wide range of models, we will discover how Grhl2 works to ensure the face and skull develop properly during birth.
Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
Targeting Sphingosine Kinase 1 To Sensitise Acute Myeloid Leukaemia To BH3 Mimetic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
Acute Myeloid Leukaemia (AML) patients are currently treated with chemotherapeutics and despite their success at achieving disease remission these responses are often short lived, resulting in relapse and death. We have identified sphingosine kinase 1 as a new drug target in AML. This proposal aims to examine the role of targeting sphingosine kinase 1 in combination with new targeted therapies in patient samples and preclinical mouse models of AML.
Inflammatory Pathways For Novel Therapeutic Interventions In Preterm Delivery
Funder
National Health and Medical Research Council
Funding Amount
$568,006.00
Summary
Preterm birth is common and carries severe risks for the child. Existing therapies are not very successful in arresting preterm labour or improving outcomes for the fetus. We have discovered that blocking inflammatory ‘sensor’ molecules can slow labour progression. This project will (1) increase our knowledge of the inflammatory pathways that initiate early labour, and (2) define the mechanism of action and safety of a new drug that has potential for delaying preterm birth in women.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.
Mab Immunotherapies For Myeloid Leukemia Patients With Germline Or Somatic RUNX1 Mutations.
Funder
National Health and Medical Research Council
Funding Amount
$766,995.00
Summary
This proposal presents preliminary evidence and proposes to confirm that 2 cell surface molecules, CD11a (ITGAL) and IL3RA (CD123) are direct (probably repression) targets of RUNX1 in HSCs, and are dysregulated in RUNX1 mutated AML. Monoclonal antibody therapies that target these two surface molecules have already passed different clinical trial phases for different diseases. We plan to show these antibodies are effective in RUNX1 positive AML in preclinical models and then clinical trials.