Research focus
Our team’s work is driven by a major unmet need, as one in three deaths in Australia are due to cardiovascular disease. In particular, heart failure has become a major clinical burden and this is only expected to worsen in our aging population. We have a particular focus on cardiac fibrosis, observed in >90% of heart failure patients, which is characterised by excessive production of extracellular matrix proteins that can prevent the heart from contracting effectively. However, the mechanisms that regulate these processes are unclear and there are currently no effective treatments for cardiac fibrosis.
Our lab uses classical pharmacology and cell signalling approaches with an innovative combination of state-of-the-art ‘omics and advanced microscopy in human heart tissue and stem cell-derived human cardiac organoids developed in the Hudson lab at QIMR Berghofer. With our extensive network of scientific and clinical collaborators across Australia and the world, we have established a cutting-edge platform for drug target discovery.
In our current research supported by the Bellberry-Viertel Senior Medical Research Fellowship, we are investigating the pathological signalling drivers of fibrosis-related cardiac dysfunction, leveraging functional analyses in human cardiac organoids and human heart tissue obtained from cardiac surgery patients from The Prince Charles Hospital. In different aspects of this program, we are interrogating global signalling networks in cardiac fibrosis using phosphoproteomics and unravelling critical paracrine signalling interactions that are dysregulated during cardiovascular disease.
We also have multiple collaborative projects, stemming from our discoveries of BET domain proteins and endothelin signalling as key mediators in inflammation-induced cardiac dysfunction (Cell, 2021, Cell Reports, 2023). These include a collaboration with ICU clinicians at Royal Brisbane and Women’s Hospital on sepsis-induced cardiac dysfunction, as well as ongoing research with Prof Martin Stone at Monash University using phosphoproteomics and CRISPR-screens to discover critical downstream signalling mediators of monocyte recruitment that could be targeted as part of novel anti-inflammatory strategies.
Gallery
Research Projects
Current Research Projects
New therapeutic targets for cardiac fibrosis.
Research Team
Funding
- Bellberry-Viertel Senior Medical Research Fellowship, “New cardiovascular therapeutics targeting fibrosis”, SR Foster, 2024-28
- NHMRC Ideas Grant, “Defining Chemotactic Signalling Networks to Identify New Anti-inflammatory Targets”, SR Foster (CIB) 2022-25
Publications
Pokhrel R, Morgan AL, Robinson HR, Stone MJ, Foster SR. Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics. Br J Pharmacol. 2024 Jul;181(14):2359-2370. doi: 10.1111/bph.16052. PMID: 36772927.
Voges HK, Foster SR, Reynolds L, Parker BL, Devilée L, Quaife-Ryan GA, Fortuna PRJ, Mathieson E, Fitzsimmons R, Lor M, Batho C, Reid J, Pocock M, Friedman CE, Mizikovsky D, Francois M, Palpant NJ, Needham EJ, Peralta M, Monte-Nieto GD, Jones LK, Smyth IM, Mehdiabadi NR, Bolk F, Janbandhu V, Yao E, Harvey RP, Chong JJH, Elliott DA, Stanley EG, Wiszniak S, Schwarz Q, James DE, Mills RJ, Porrello ER, Hudson JE. Vascular cells improve functionality of human cardiac organoids. Cell Rep. 2023 May 30;42(5):112322. doi: 10.1016/j.celrep.2023.112322. PMID: 37105170.
Mills RJ, Humphrey SJ, Fortuna PRJ, Lor M, Foster SR, Quaife-Ryan GA, Johnston RL, Dumenil T, Bishop C, Rudraraju R, Rawle DJ, Le T, Zhao W, Lee L, Mackenzie-Kludas C, Mehdiabadi NR, Halliday C, Gilham D, Fu L, Nicholls SJ, Johansson J, Sweeney M, Wong NCW, Kulikowski E, Sokolowski KA, Tse BWC, Devilée L, Voges HK, Reynolds LT, Krumeich S, Mathieson E, Abu-Bonsrah D, Karavendzas K, Griffen B, Titmarsh D, Elliott DA, McMahon J, Suhrbier A, Subbarao K, Porrello ER, Smyth MJ, Engwerda CR, MacDonald KPA, Bald T, James DE, Hudson JE. BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection. Cell. 2021 Apr 15;184(8):2167-2182.e22. doi: 10.1016/j.cell.2021.03.026. PMID: 33811809.
Further Information
- Professor Martin Stone (Monash University)
- Professor Wally Thomas (The University of Queensland)
- Associate Professor Alexander Hauser (University of Copenhagen)
- Professor Anthony Davenport (University of Cambridge)
- Dr Lauren May (Monash Institute of Pharmaceutical Sciences)
- Professor Paul Timpson (Garvan Institute)
- Dr Wandy Chan (The Prince Charles Hospital)
- Professor Peter Molenaar (The Prince Charles Hospital)
- Professor John Atherton (Royal Brisbane and Women's Hospital)
- Associate Professor Jayesh Dhanani (Royal Brisbane and Women's Hospital)
- Professor Ralf Schittenhelm (Monash University)
- Professor Kaylene Simpson (Victorian Centre for Functional Genomics)
- Professor Tracy Handel (University of California San Diego)
- Associate Professor Irina Kufareva (University of California San Diego)
- Associate Professor Nicola Smith (University of NSW)
- Dr Natasha Grimsey (University of Auckland)