Medcalf Group - Molecular Neurotrauma, Haemostasis

Key terms: Fibrinolysis, stroke, traumatic brain injury (TBI)

2022 group L-R: Back row - Zikou (Oscar) Liu, Ahnaf Hossain, Sayan Thuraisamy, Rob Medcalf, Front row - Fiona McCutcheon, Joanne Chia, Heidi Ho, Charithani (Cherry) Keragala; Yunxin (Cindy) Xiao, Rachel Waring

Group Leader - Prof Robert Medcalf

Prof Robert Medcalf is deeply interested in fibrinolysis - the process our bodies implement to remove blood clots. He is investigating how we can use our natural clot busting mechanisms to help treat stroke victims. His interest is in the chemicals in our bodies that can help reduce the long-term damage of stroke and also in other diseases of the brain including traumatic brain injury.

Find out more about Prof Robert Medcalf

Meet the team

Research overview

Projects and opportunities

Sabbatical visits by international scientists

Contractual research with biotech firms

Fellowship and grant awards

NH&MRC Fellowships

1993-1997 NH&MRC R.D. Wright Fellowship (#937703) Medcalf, R.L. Amount $225,680; Title: Molecular and cellular biology of t-PA and PAI-2 gene expression.

2003-2007 NH&MRC Senior Research Fellowship Level A (#236860) Medcalf, R.L. Amount $614,750

2008-2012 NH&MRC Senior Research Fellowship Level A (#491088). Medcalf, R.L. Amount $623,553.
2013-2017. NH&MRC Principle Research Fellowship (PRF) APP1044152. Medcalf RL (CI-A). Amount: $714,745

Previous NHMRC project Grants

1994-1996: NH&MRC (#940415). Investigator Medcalf, R.L. (CI-A) Amount: $172,140; Title: Regulation of plasminogen activator and plasminogen activator inhibitor gene expression.

1994-1996: NH&MRC Investigators: Salem, H (CI-A). Medcalf, R.L. (CI-B). Coughlin P, Bird, P. Amount: $181,200; Title: Characterisation and molecular biology of a novel proteinase inhibitor.

1997-1999 NH&MRC #970419 Investigators: Medcalf, R.L (CI-A). Shen, Y. Amount:$197,700; Title: Transcriptional regulation of the fibrinolytic system

1999-2001 NH&MRC #980862 Investigators: Medcalf, R.L (CI-A). Maurer, F. Amount/yr: $345,000; Title: Regulation of the PAI-2 gene.

1999-2001 NH&MRC #990219. Investigators: Medcalf, R.L (CI-A). Costa, M. Amount: $390,000; Title: Molecular control of fibrinolysis

2000-2002 NH&MRC #124316. Investigators: Medcalf, R.L. (CI-A) Amount/yr: $240,000; Title: Regulation of tissue-type plasminogen activator gene expression in endothelial cells and in transgenic mice.

2000-2002 NH&MRC #124315. Investigators: Medcalf, R.L. (CI-A). Carter, A. Amount: $210,000; Title: The molecular basis for the increased incidence of thrombosis associated with the prothrombin G20210A gene polymorphism

2001-2003. NH&MRC #143615. Investigators: Medcalf, R.L (CI-A). Yu, H. Amount: $241,527; Title: Post-transcriptional regulation of the plasminogen activator inhibitor type 2 gene.

2003-2005 NH&MRC #236862. Investigators: Medcalf, R.L. (CI-A), Costa M. Amount/yr: $490,500; Title: Molecular Mechanisms for the cell-type specific regulation of the tissue-type plasminogen activator gene.

2004-2006 NH&MRC #248250. Investigators: Medcalf, R.L. (CI-A), Yu, H. Amount: $318,000; Title: Post-transcriptional regulation of plasminogen activator inhibitor type 2 gene expression.

2008-2010 NH&MRC #491152 Investigators: Medcalf, R.L. (CI-A). Amount: $504,098; Title: Role and regulation of tissue-type plasminogen activator in the central nervous system.

2008-2010 NH&MRC #491151. Investigators: Medcalf, R.L. (CI-A) Stasinopoulos S, Nagamine Y. Amount: $508,838; Title: Post-transcriptional regulation of plasminogen activator inhibitor type 2.

2009-2011 NH&MRC #566776 Investigators: Stewart, A.G., Medcalf, RL (CIB), Hughes, R.A., Banwell, M.G. Amount: $368,025; Title: 2-Methoxyestradiol analogues: prototype modulators of annexin II-dependent plasminogen activation. Total: $390,000

2010-2012 NH&MRC #APP606658 Investigators: Medcalf, RL (CI-A), Lawrence DA. Title: “To determine the means by which plasminogen activators modulate integrity of the blood brain barrier”. Total: $514,018

2010-2012 NH&MRC #APP606659 Investigators: Medcalf, RL (CI-A), Bottomley, S., Samson, A. Title: “To investigate how the aggregation of proteins during neuronal injury promotes neurotoxic plasmin formation”. Total: $576,250

2010-2012 NH&MRC #APP606660 Investigators: Medcalf, RL (CI-A). Title: “To understand the role of the plasminogen activating and matrix metalloproteinase systems in traumatic brain injury”. Amount $490,644

2013-2015. NHMRC #APP1045755 Investigators: Medcalf, R.L. (CI-A), Lawrence DL (CI-B). Title: How enzymes and enzyme inhibitors effect the brain after traumatic brain injury. Amount: $592,143.

2013-2015. NHMRC# APP1045756 Investigators: Medcalf, R.L. (CI-A), Michell, A. (CI-B). Title: How can we improve the way blood clots are removed in ischaemic stroke? Amount: $565,847

2013-2016 (extended to 2017) NHMRC #APP1044894. Investigators: Gruen, R.,(CI-A), Mitra, B. (CI-B), Bernard, S (CI-C), Jacobs, I (CI-D), Medcalf, R.L. (CI-E), Reade, M (CI-F), Tran, H (CI-G). Title: Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH Study). Amount $1,668,152.

2017-2020 NHMRC #APP1126636 Investigators: Medcalf, R.L., (CI-A), Plebanski, M., Boyd, B,. Gruen, R., Roberts, I., and Tran, H. Title: The effect of anti-fibrinolytic drugs on blood-brain barrier integrity and the immune response in traumatic brain injury. Amount $870,476.

2018-2021 NHMRC #APP1141046. Investigators: Nandurkar, H., Medcalf, R.L (CI-B) and Robson, S. Targeted delivery of CD39 to the ischaemic brain improves outcomes in stroke. Amount $895,780

Total previous NHMRC funding: $10,349,338

Currently held NHMRC grants:

2019-2022 NHMRC #APP1156506. Investigators: Medcalf, R.L., (CI-A), Boyd, B, Cloud, G. Title: Improving the safety and efficacy of thrombolytic therapy in acute ischaemic stroke. Amount $1,371,900.

2020-2024, NHMRC #APP1185145. Investigators: Myles, P., Medcalf, R.L (CI-B), Brown, W., Peel, T., and Kasza, J. Title: Tranexamic acid to Reduce Infection after Gastrointestinal Surgery – the TRIGS Trial. Budget $5.196m.

Currently held MRFF grants:

2022-2026. MRF2014406 MRFF - Rare Cancers, Rare Diseases and Unmet Need (RCRDUN). Title: “Accelerating clot lysis in ischemic stroke with dornase alfa in an Umbrella Bayesian Optimised Phase 2 trial”. Campbell, B. C. V. (CI-A), Churilov, L., Medcalf, R (CI-C)., Alemseged, F., Kleinig, T., Dewey, H., Delcourt, C., Mitchell, P., Donnan, G. & Davis, S. M. $1.453m

Publications

Medcalf publication accolade
Editorial by Prof Medcalf on "Fibrinolysis and Trauma Outcomes" published in Anesthesiology, Jan 2022
- Download Pdf (438 KB)
- Article webpage
- Podcast transcript

Selected publications

For Improved Method for the Preparation of a Human Cell-based, Contact Model of the Blood-Brain Barrier video please click here

Mutimer, C., Keragala, C. B., Markus, H.S., Werring, D.J., Cloud, G.C., and Medcalf, R.L. (2021) Cerebral amyloid angiopathy and the fibrinolytic system: is plasmin a therapeutic target? Stroke 52(8):2707-2714. doi: 10.1161/STROKEAHA.120.033107
Medcalf, R.L. Keragala, C.B., and Myles, P.S. (2020). Fibrinolysis and COVID-19: A plasmin paradox. J Thromb Haemost. Sep;18(9):2118-2122. doi: 10.1111/jth.14960
Daglas, M, Galle, A., Draxler, D.F., Sashindranath, M., and Medcalf, R.L. (2020). Sex-dependent effects of tranexamic acid on blood-brain barrier permeability and the immune response following traumatic brain injury in mice. J Thromb Haemost Oct;18(10):2658-2671. doi: 10.1111/jth.15015.
Draxler, D.F., Yep, K., Hanafi, G., Winton, A., Daglas, M., Ho, H., Sashindranath, M., Wutzlhofer, L.M., Forbes, A., Goncalves, I., Tran, H., Wallace, S., Plebanski, M., Myles, P.S., Medcalf, R.L. (2019). Tranexamic acid modulates the immune response and reduces post-surgical infection rates. Blood Advances, 28;3(10):1598-1609. doi: 10.1182/bloodadvances.2019000092.
Daglas, M, Draxler, D.F., Ho, H., McCutcheon, F., Galle, A, Au, A-E, Larsson, P., Gregory, J., Alderuccio, F., Sashindranath, M, Medcalf, R.L. (2019). Activated CD8+ T cells cause long-term neurological dysfunction following traumatic brain injury. Cell Reports, Oct 29;29(5):1178-1191.e6. doi: 10.1016/j.celrep.2019.09.046
Draxler, D.F., Lee, F., Ho, H., Keragala, C.B., Medcalf, R.L., Niego, B. (2019). t-PA suppresses the immune response and aggravates neurological deficit in a murine model of ischemic stroke. Frontiers Immunol. 10:591. doi: 10.3389/fimmu.2019.00591. eCollection 2019.
Draxler, D.F., Daglas, M., Fernando, A., Hanafi, G., McCutcheon, F., Ho, H., Galle, A., Au, A.-E., Niego, B., Wilson, K., Plebanski, M., Sashindranath, M., Medcalf, R.L. (2019). Tranexamic Acid Modulates the Cellular Immune Profile after Traumatic Brain Injury in Mice without Hyperfibrinolysis. J Thromb Haemost. 17(12):2174-2187 doi:10.1111/jth.14603.

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