Hamilton Group - Platelets & Thrombosis
Key terms: Discovering novel anti-thrombotics
2020 group L-R Back row: Associate Professor Justin Hamilton, Dr Mitch Moon, Front Row: Ms Simeng Li, Ms Natasha Setiabakti, Ms Nurul Aisha Zainal Abidin, Dr Pia Larsson, Ms Deviena Nabila, Absent: Ms Volga Tarlac
To understand platelet activation mechanisms in order to rationalise the development of novel anti-platelet agents for the prevention of arterial thrombosis.
Arterial thrombosis, manifesting predominantly as acute myocardial infarction or ischaemic stroke, is by far the most common cause of death and disability in Australia. Activated platelets are the essential cellular component of arterial thrombi and anti-platelet drugs are the mainstay of current pharmacotherapy for the prevention of arterial thrombosis. Consequently, there is substantial need for novel strategies to inhibit platelet function for the prevention of heart attack and stroke. Our research examines the cell biology of blood platelets and their precursor cell, the megakaryocyte, in order to understand the mechanisms by which platelets are produced and function, since examining the mechanisms of platelet production and function is likely to reveal novel approaches for pharmaceutical platelet inhibition.
A/Prof Justin Hamilton is a senior researcher at the ACBD who has received significant research support from the Heart Foundation over the past decade. Listen to his account of the current research he is undertaking, why he got into cardiovascular research and what you can do to help support the Heart Foundation in its ongoing fight against cardiovascular disease. (Videos courtesy the Heart Foundation)
- Defining the function of the thrombin receptor, PAR4, on human platelets.
- Investigating the role of Class II PI3Ks in platelet production and function.
Projects and Grant Funding
Our work is funded by the ARC, NHMRC, NHFA and the CASS Foundation.
- Title: Examining novel cell signalling in the regulation of platelet structure and function.
Investigators: Hamilton, J
Funding: (2014 - 2017). Australian Research Council (ARC).
- Title: Defining the function of the thrombin receptor, PAR4, on human platelets.
Investigators: Hamilton, J
Funding: (2013 - 2015). National Health & Medical Research Council (NHMRC).
- Title: Nikon AIR Confocal Microscope.
Investigators: Jackson, S, Medcalf, R, Mackay-Fisson, F, Plebanski, M, Andrews, R, Jane, S, Curtis, D, Morganti-Kossmann, M, Peter, K, Chin-Dusting, J, Mak, J, Pereira, C, Hamilton, J, Cody, S
Funding: (2011 - 2015). National Health & Medical Research Council (NHMRC).
- Selvadurai M.V, Moon, J.J, Mountford S.M, Ma X, Zheng Z, Jennings I.G, Setiabakti N.M, Iman R.P, Brazilek R.J, Abidin N.A.Z, Chicanne G, Severin S, Nicholls A.J, Wong H.Y, Rinckel J-Y, Eckly A, Gachet C, Nesbitt W.S, Thompson P.E, Hamilton J.R. Disrupting the platelet internal membrane via PI3KC2α inhibition impairs thrombosis independently of canonical platelet activation. Science Translational Medicine, 22 Jul 2020, 12(553),eaar8430.
- Zheng Z, Pinson J-A, Mountford S.J, Orive S, Schoenwaelder S.M, Shackleford D, Powell A, Nelson E.M, Hamilton J.R, Jackson S.P, Jennings J.G, Thompson P.E. Discovery and antiplatelet activity of a selective PI3Kβ inhibitor (MIPS-9922). European Journal of Medicinal Chemistry, 2016:122, 339-351
- French S.L, Paramitha A.C, Moon M.J, Dickins R.A, Hamilton J.R. Humanizing the protease-activated receptor (PAR) expression profile in mouse platelets by knocking Par1 into the Par3 locus reveals Par1 expression is not tolerated in mouse platelets. PLoS One, 2016:11(10) Article number e0165565
- French S.L, Arthur J.F, Lee H, Nesbitt W.S, Andrews R.K, Gardiner E.E, Hamilton J.R. Inhibition of protease-activated receptor 4 impairs platelet procoagulant activity during thrombus formation in human blood. Journal of Thrombosis and Haemostasis, 2016:14(8) 1642-1654
- Petitjean C, Setiabakti C.M, Mountford J.K, Arthur J.F, Ellis S, Hamilton J.R. Combined deficiency of PI3KC2α and PI3KC2β reveals a nonredundant role for PI3KC2α in regulating mouse platelet structure and thrombus stability. Platelets, 2016:27(5) 402-409
- Mountford J.K, Petitjean C, Putra H.W.K, McCafferty J.A, Setiabakti N.M, Lee H, Tonnesen L.L, McFadyen J.D, Schoenwaelder S.M, Eckly a, Gachet C, Ellis S, Voss A.K, Dickins R.A, Hamilton J.R, Jackson S.P. The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function. Nature Communications, 2015:6, Article number 6535