Our objective

Our mission is to identify and gain insights from the genetic and molecular pathways involved in atherosclerotic disease in which the build-up of plaque in blood vessels causes thrombotic events including heart attacks. We aim to exploit these pathways to improve therapies with the aim of eradicating atherosclerotic diseases.

Our main objective is to broaden understanding of the cellular and molecular mechanisms involved in blood vessel wall patterning and define the role of these pathways in vascular abnormalities and complications. We continue to link these insights into translational research to prevent and treat atherosclerosis in humans.

To this end, we employ a unique blending of exclusive pre-clinical models and cultured cells, as well as human samples, with the aim of unveiling the pathogenesis of atherosclerosis.

Our ultimate goal is to prevent and reverse certain vascular diseases to prevent heart attacks and strokes.

Our impact

Atherosclerotic cardiovascular disease is the leading cause of death globally, accounting for approximately one third of all deaths. Currently available therapies are not universally effective and do not reverse vascular disease completely, resulting in premature deaths and reduced quality of life for disease sufferers. With the need for continued treatment, there is a large burden on the health care system. Our work to identify the factors and signalling mechanisms involved in cardiovascular disorders has the potential to improve treatment options and eradicate atherosclerotic disease, thus increasing life spans and decreasing its burden on society.

Collaborators

Assoc Prof Sanjay Patel – Anti-inflammatory therapy on atherosclerosis (Royal Prince Alfred Hospital (RPAH), HRI)

Prof Edward Fisher – Lipid lowering therapy on atherosclerosis (New York University (NYU) School of Medicine)

Prof Mark Cooper – Diabetes as a risk factor in atherosclerosis (Diabetes Department, Monash University)

Prof Girish Dewivedi – Inflammation in atherosclerosis (University of Western Australia)

Assoc Prof Peter Psaltis – Inflammation and stem cells in atherosclerosis (Adelaide Medical School, The University of Adelaide)

Dr Florent Ginhoux – Inflammation in vascular disease (Singapore Immunology Network (SIgN), A*STAR)

Prof Shirley Jansen – Inflammation in atherosclerosis (Vascular and Endovascular Surgery at Sir Charles Gairdner Hospital and University of Western Australia)

Ed Brackenreg – Engineering a physiologically-relevant blood vessel in vitro (CEO Codex Research Pty Ltd)

Selected publications

Williamson A, Toledo D, Liyanage S, Hassanshahi M, Catherine Dimasi1, Nisha Schwarz1, Sanuja Fernando1,2, Salagaras T, Long A, Di Bartolo BA, Kazenwadel J, Harvey N,. Drummond G, Vinh A, Chandrakanthan V, Misra A, Tan J, Bonder C, Nicholls SJ, Bursill CA, Psaltis PJ. Self-renewing tissue-resident endothelial-macrophage progenitor cells originate from yolk sac and are a local source of inflammation and neovascularization in postnatal aorta. Nature Communications 2024 Aug 17;15(1):7097

Lin A., Miano J., Fisher EA, Misra A. Chronic inflammation and vascular cell plasticity in atherosclerosis. Nature cardiovascular research 2024 Dec;3(12):1408-1423.

Misra A, Psaltis PJ, Mondal AR, Nelson AJ, Nidorf SM. Implications and limitations of the CLEAR-SYNERGY trial for the use of low-dose colchicine in cardiovascular disease. Nature Cardiovascular Research Jan 24. doi: 10.1038/s44161-024-00600-2. Online ahead of print.

Li W, Lin A, Hutton M, Dhaliwal H, Nadel J, Rodor J, Tumanov S, Örd T, Hadden M, Mokry M, Mol BM, Pasterkamp G, Padula MP, Geczy CL, Ramaswamy Y, Sluimer JC, Kaikkonen MU, Stocker R, Baker AH, Fisher EA, Patel S, Misra A. Colchicine promotes atherosclerotic plaque stability independently of inflammation. bioRxiv2023 Oct 3:2023.10.03.560632.

Thevkar P., Rawal S., Fnu S., Choudhury R., Misra A*. HDL regulates TGFß-receptor lipid raft partitioning, restoring contractile features of cholesterol-loaded vascular smooth muscle cells. Fisher EA*. (Co-corresponding author).

Yen Chin Koay YC, Cao Y, Tomita S, Bai AY, Hunter B, Misra A, Lal S, Lusis AJ, Kaye DM, Larance M, O’Sullivan JF. The heart has intrinsic ketogenic and ketolytic capacity that can be augmented therapeutically in HFpEF using NAD+ repletion. Circulation Research (Accepted).

Role of Colchicine in Atherosclerosis. Frontiers in Cardiovascular Medicine 2024 Nov 21:11:1516185.

Misra A, Rehan R, Lin A, Patel S, Fisher EA. Emerging Concepts of Vascular Cell Clonal Expansion in Atherosclerosis. Arterioscler Thromb Vasc Biol. 2022 Feb 3;:ATVBAHA121316093. doi: 10.1161/ATVBAHA.121.316093. [Epub ahead of print] PubMed PMID: 35109671.

Misra A, Fisher EA. Tipping the cap away from danger. Nature Metabolism, 2021 Feb;3(2):128-130.

Misra A, et al. Translational research in culture: AADCA, diabetes and cardiovascular disease. Cell Stem Cell, 2020 Jul 2;27(1):6-7. doi: 10.1016/j.stem.2020.06.012

Misra A, et al. Integrin beta3 regulates clonality of smooth muscle-derived atherosclerotic plaque cells. Nature Communications, (2018), May 25;9(1):2073.

Dave JM, Chakraborty R, Ntokou A, Saito J, Saddouk FZ, Feng Z, Misra A, Tellides G, Riemer RK, Urban Z, Kinnear C, Ellis J, Mital S, Mecham R, Martin KA, Greif DM. JAGGED1/NOTCH3 activation promotes aortic hypermuscularization and stenosis in elastin deficiency. J Clin Invest. 2022 Jan 6;. doi: 10.1172/JCI142338. [Epub ahead of print] PubMed PMID: 34990407.