Garvan Institute of Medical Research

Tracking CDK1 Dynamics With a Novel Biosensor Mouse and Clinical Cohorts to Predict CDK4/6 Inhibitor Sensitivity in ER+ Breast Cancer

ABSTRACT High‐risk estrogen receptor positive (ER+) early breast cancer (EBC) is managed with endocrine therapies and cyclin‐dependent kinase (CDK) 4/6 inhibitors, although no standard molecular markers clinically identify these tumors. CDK1 lies immediately downstream of CDK4/6...

Multiscale mechanical analysis of live breast cancer spheroids by micro‐compression and Brillouin imaging

Abstract Recent developments in cancer mechanobiology have highlighted the importance of tumour mechanics as a potential marker of disease progression. Three‐dimensional tumour models provide simplified yet physiological relevance exhibiting mechanical heterogeneity. However, com...

hpci improves reproducibility of computational biology research by integrating Continuous Integration with High Performance Computing clusters

Abstract Motivation The reproducibility crisis in bioinformatics and computational biology can be mitigated by using Continuous Integration (CI), a proven software engineering practice, to automate the testing of analysis pipelines and models. However, the adoption of CI in bioin...

Engineering Antibody Evolution: Germline‐Targeting HIV Vaccines Reach a Turning Point

This commentary examines three recent Nature studies demonstrating a conceptual shift in HIV vaccine design, demonstrating how germline-targeting HIV vaccines can progress beyond expanding rare broad neutralizing antibody (bnAb) precursors to deliberately guiding their affinity m...

Key considerations for window of opportunity trials and preoperative endocrine therapy in breast cancer

Window of opportunity (WOO) trials are short, pre-surgical trials which aim to evaluate novel therapeutic strategies and answer biological and mechanistic questions. Despite their relative simplicity, their conduct can be challenging. This Perspectives Article considers key facto...

Patient perspectives on cardioprotective medication during breast cancer treatment

Cardiotoxicity remains a key concern of HER2-directed therapies, with no proven prevention strategies. The success of cardioprotective interventions will depend not only on efficacy, but on patient acceptability, an underexplored determinant of trial participation and clinical im...

Insulin‐Like Growth Factor Axis and Survival in Metastatic Hormone‐Sensitive Prostate Cancer: Post‐Hoc Analysis From the ENZAMET Phase 3 Trial

ABSTRACT Background A higher ratio of IGF‐1:IGF binding protein 1 (IGFBP1) was associated with improved prognosis in the CHAARTED trial of docetaxel in participants with metastatic hormone‐sensitive prostate cancer (mHSPC). The ENZAMET trial demonstrated the survival benefit of a...

Combining Implementation and Data Sciences to Accelerate Evidence Integration into Healthcare – ImpleMATE

Background The translation of research evidence into routine healthcare practice is often slow and inconsistent, even timely implementation can significantly improve patient outcomes. While implementation science offers strategies to close this gap, current approaches are frequen...

Human-inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity

Abstract We previously reported inherited RORγT deficiency in seven patients from three ancestries (Chilean, Palestinian, Saudi Arabian) with mycobacterial disease and chronic mucocutaneous candidiasis (CMC). We report here five additional patients from different ancestries (Afgh...

Weighted sliced inverse regression for scalable supervised dimensionality reduction of spatial transcriptomics data

Abstract With the dramatic take-up of spatially resolved transcriptomics biotechnologies, performing spatially-aware analysis of the resulting data is crucial to maximise advances in biological understanding. Dimensionality reduction is a first step in almost any analysis of spat...

Oxygen-dependent subcellular redistribution of PHD3 links the hypoxic microenvironment to mitochondrial metabolic reprogramming in ccRCC

Abstract Clear cell renal cell carcinoma (ccRCC) is characterized by profound metabolic dysregulation, with both prolyl hydroxylase domain protein 3 (PHD3) and pyruvate carboxylase (PC) independently implicated in disease progression. Although each influences patient outcomes, a...

Tracking breast cancer progression using Methylscape

Abstract Cancer progression is intricately driven by epigenetic reprogramming, where aberrant DNA methylation patterns reshape gene regulation and cellular phenotypes. These alterations include promoter hypermethylation of tumour suppressor genes and global hypomethylation, colle...

Cell-type-specific eQTLs underlie the genetic architecture of complex traits

Genetic effects on complex traits primarily act by regulating gene expression; however, this process is not well understood1. Studies of genetic effects on gene expression (expression quantitative trait loci (eQTLs)) can inform as to the gene regulatory layer between genetic vari...

Detecting somatic mutations in rare clones using single-cell multiomics

Abstract Background Somatic mutations are increasingly recognised as drivers of diseases beyond cancer, including autoimmune disorders. However, identifying rare, cell type-specific causal mutations remains challenging due to their low frequency within heterogeneous cell populati...

Stochasticity in response to rostrocaudal and mediolateral determinants influences inaccurate specification within kidney organoids

The differentiation of human pluripotent stem cells to kidney requires the accurate recapitulation of complex morphogenetic patterning events within an in vitro environment. Current protocols are assumed to accurately pattern through intermediate mesoderm to kidney with outcomes...