Professor Robert Medcalf
Phone: +61 3 99030133
Fax: +61 3 99030228
- Group Leader, Fibrinolysis and Gene Regulation Laboratory
- NH&MRC Senior Research Fellow
Robert Medcalf was awarded his Ph.D. from the University of Melbourne in 1984. His first post-doctoral appointment was at the University of Melbourne where he investigated the role of the plasminogen activating system in rheumatoid arthritis. In 1986, he continued his research in Lausanne, Switzerland where he extended his interest in the field of plasminogen activation and fibrinolysis. In 1993, he returned to Australia where he established a laboratory at Monash University in Melbourne. He was appointed as a NHMRC Senior Research Fellow in 2003. He has published more than 90 papers in peer reviewed journals on fibrinolysis and plasminogen activation and has an H-index of 30. Since 2000, his research has attracted more than $7m in peer reviewed funding from the NHMRC, the National Heart Foundation, the Brain Research Foundation and the Victorian Neurotrauma Initiative. He was elected as Chairman of the International Society on Fibrinolysis and Proteolysis (ISFP) in 2004 and in 2008 and he will also be Congress President of the 2019 meeting of the International Society on Thrombosis and Haemostasis (ISTH) in Melbourne. He is Associate Editor of the Journal of Thrombosis and Haemostasis which is the flagship journal of both the ISFP and the ISTH and is on the Editorial Board of the Journal of Biological Chemistry.
His laboratory has a major focus on investigating the role of the fibrinolytic system in the central nervous system. He has a particular interest in understanding how the fibrinolytic protease, tissue type plasminogen activator (t-PA) potentiates neuronal injury and modulates blood brain barrier permeability and the relationship of this on the use of t-PA and related thrombolytic agents in ischaemic stroke. His laboratory is also exploring the influence of the fibrinolytic system in traumatic brain injury and in models of neurodegeneration. Other interests include the mechanism by which t-PA functions enzymatically in the brain. He is also interested in exploring the role of platelet derived products on neuronal function, how clot formation in the brain may modulate brain function in addition to causing ischaemia and a new project exploring the role of plasminogen activation in multiple sclerosis.
Projects and Opportunities
- To determine how fibrinolytic enzyme modulate blood brain barrier permeability
- To identify and characterise factors released from platelets during clot formation that modulate neuronal function
- To explore the mechanism by which plasminogen activators and matrix metalloproteinases modulate neurovascular permeability following brain trauma
- To determine the role of tissue-type plasminogen activator in the pathogenesis of multiple sclerosis
Liberatore, G.T., Samson, A., Bladin, C., Schleuning, W.D., and Medcalf, R.L. (2003). Vampire bat salivary plasminogen activator (desmoteplase) – a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke 34: 537-543. IF=7.041
Samson, A.L., and Medcalf, R.L. (2006). Tissue-type plasminogen activator: a multifaceted modulator of neurotransmission and synaptic plasticity. Neuron 50:673-678. IF: 14.027
Samson, A.L., Nevin, S.T., Croucher, D., Niego, B., Daniel, P.B., Weiss, T.W., Moreno, E., Monard, D., Lawrence, D.A., and Medcalf, R.L. (2008). Tissue-type plasminogen activator requires a co-receptor to enhance N-Methyl-D-Aspartate receptor function. J Neurochem. 107: 1091-1101. IF: 4.337
Samson, A.L., Borg, R.J., Niego, B, Wong, C.H., Crack, P.J. Yongqing, T., and Medcalf, R.L. (2009). A non-fibrin macromolecular cofactor for tPA-mediated plasmin generation following cellular injury. Blood, 114: 1937-46. IF: 10.558
Sashindranath, M.*, Samson, A.L*, Downes, C.E., Crack, P.J., Lawrence, A.J. Li, Q.-X. Ng, A.Q.P., Jones, N.C., Farrugia, J., Abdella, E., Vassalli, J-D., Madani, R., Medcalf, R.L. *Denotes equal first author (2011) Compartment- and context-specific changes in tissue-type plasminogen activator (tPA) activity following brain injury and pharmacological stimulation. Lab Invest 91: 1079-91. IF: 4.405
Medcalf, R.L. (2011). Plasminogen activator inhibitor type 2: still an enigma but a model for gene regulation. Methods Enzymol, 499: 105-134
Niego, N., Puschmann, T.B., Turnley, A.M., Medcalf, R.L. (2012). t-PA-specific modulation of a human BBB model involves plasmin-mediated activation of the Rho-kinase pathway in astrocytes. Blood (in press). IF: 10.558
Medcalf, R.L. (2012). Desmoteplase: discovery, insights and opportunities for ischaemic stroke. Br J Pharmacol 165(1):75-89. IF: 4.925
Current Project Funding
- Agency: NH&MRC project grant #606658 (2010-2012). “To determine the means by which plasminogen activators modulate integrity of the blood brain barrier”. Investigators: Medcalf, RL (CI-A), Lawrence DA.
- Agency: NH&MRC project grant #606659 (2010-2012). “To investigate how the aggregation of proteins during neuronal injury promotes neurotoxic plasmin formation”. Investigators: Medcalf, RL (CI-A), Bottomley, S., Samson, A
- Agency: NH&MRC project grant #606660 (2010-2012). “To understand the role of the plasminogen activating and matrix metalloproteinase systems in traumatic brain injury”. Investigator: Medcalf, RL (CI-A)