Discovering a new biological universe

Professor 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"

In 2020 the School of Translational Medicine, Monash University, introduced a Translational Stream within the Master of Clinical Research. An elective translational medicine unit within the course, TRM6004 Clinical and Translational Haematology and Immunology which is also cross-listed within the Translational Research PhD program at the CCS. Prof Medcalf was invited to lecture into this unit, to contribute his expert knowledge and the findings of his translational studies in fibrinolysis. 
Prof Medcalf has made significant contributions within TRM6004 in regard to designing and  delivering 2 graduate level lectures on fibrinolysis, plasminogen and anti-fibrinolytic agents and  how his research translates within the clinic. 
Notably, Prof Medcalf led the design of an entire module within the unit as the coordinator of the  Fibrinolysis and Stroke module. 
Prof Medcalf has been actively engaged with other contributors to the Fibrinolysis and Stroke module to ensure all content and its delivery is consistent to a graduate level and meets the learning outcomes.