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Discovering a new biological universe

Senior Research Fellow 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 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.

Fibrinolysis gets its name from a protein called fibrin which gives a blood clot its physical texture.

'A lot of the time, we need to [form clots] because we hurt ourselves,' Robert explains. 'That's just normal, but as we get older, our blood vessels start decaying to some extent, and blood clots start forming at sites which are inappropriate, because it's viewed [by our body] as a wound. Then you're in all sorts of trouble - strokes, heart attacks, deep vein thrombosis, and so on.'

To treat such ailments, doctors will often give megadoses of the body's natural clot removing enzyme, TPA - tissue plasminogen activator - to remove the clot. However, for stroke victims, TPA is only useful within a four and a half hour 'window' after stroke onset. This severely limits the scope of treatment. and part of Robert's work is to try to extend this window.

'If you get to the hospital early enough, TPA is good. After that, it becomes precarious. We've been looking into lengthening the time line by which doctors can still administer TPA. Some trials are going to six hours, and others are going to nine hours. At those kinds of rates, rather than a 15 per cent chance, you would start having a 20 to 25 per cent chance of doctors treating you with TPA, maybe even more. That's a tremendous improvement.'

However, TPA may have applications beyond its role as a stroke-treatment agent. Indeed, Robert suggests that clot busting may be TPA's secondary purpose.

'TPA can influence the permeability of the blood-brain barrier. It's very important in memory formation and plasticity on learning . It even acts as a neurotransmitter. [It's capable of] all sorts of surprising things.'

To understand the effects and value of TPA better, Robert is extending his research beyond human physiology - and to that of Desmodus rotundus: the common vampire bat.

'There's this TPA molecule derived from the vampire bat that has no damaging brain effect whatsoever - at least in preliminary tests - and this has offered some interesting possibilities for stroke treatment.

"We are also very interested in applying our knowledge to see how t-PA is influencing other brain conditions, including traumatic brain injury, epilepsy and even in multiple sclerosis. It is a very exciting time to be in research"


Research area keywords

  • Fibrinolysis
  • Haematology
  • Stroke
  • Traumatic Brain Injury (TBI)

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Projects 2000 2024

Research Output 1980 2019

1 Citation (Scopus)

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice

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., 29 Oct 2019, In : Cell Reports. 29, 5, p. 1178-1191.e6 20 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
2 Citations (Scopus)

Fibrinolysis Shutdown in Trauma: Historical Review and Clinical Implications

Moore, H. B., Moore, E. E., Neal, M. D., Sheppard, F. R., Kornblith, L. Z., Draxler, D. F., Walsh, M., Medcalf, R. L., Cohen, M. J., Cotton, B. A., Thomas, S. G., Leeper, C. M., Gaines, B. A. & Sauaia, A., 1 Sep 2019, In : Anesthesia and Analgesia. 129, 3, p. 762-773 12 p.

Research output: Contribution to journalReview ArticleResearchpeer-review

2 Citations (Scopus)

T-PA suppresses the immune response and aggravates neurological deficit in a murine model of ischemic stroke

Draxler, D. F., Lee, F., Ho, H., Keragala, C. B., Medcalf, R. L. & Niego, B., 27 Mar 2019, In : Frontiers in Immunology. 10, MAR, 12 p., 591.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
1 Citation (Scopus)

Tranexamic Acid Influences the Immune Response, but not Bacterial Clearance in a Model of Post-Traumatic Brain Injury Pneumonia

Draxler, D. F., Awad, M. M., Hanafi, G., Daglas, M., Ho, H., Keragala, C., Galle, A., Roquilly, A., Lyras, D., Sashindranath, M. & Medcalf, R. L., 1 Dec 2019, In : Journal of Neurotrauma. 36, 23, p. 3297-3308 12 p.

Research output: Contribution to journalArticleResearchpeer-review

Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis

Draxler, D. F., Daglas, M., Fernando, A., Hanafi, G., McCutcheon, F., Ho, H., Galle, A., Gregory, J., Larsson, P., Keragala, C., Wright, D. K., Tavancheh, E., Au, A. E., Niego, B., Wilson, K., Plebanski, M., Sashindranath, M. & Medcalf, R. L., Dec 2019, In : Journal of Thrombosis and Haemostasis. 17, 12, p. 2174-2187 14 p.

Research output: Contribution to journalArticleResearchpeer-review