Traumatic Brain Injury seminar - Monday 7th March, room 204
MME 2001 graduate, Dr John D. Finan, Northshore University, Chicago, gives a talk entitled "Mechanisms and Treatment of Traumatic Axonal Injury". This highlights groundbreaking research in the field of traumatic brain injury (TBI) which is the the leading cause of death among young people in the developed world.
Traumatic brain injury (TBI) is the leading cause of death among young people in the developed world and a substantial cause of morbidity among those who survive. More than 30 clinical trials have been conducted with candidate therapies for TBI and all have failed, despite the fact that most were supported by promising, pre-clinical, rodent data. This uniform failure indicates that new pre-clinical tools are needed that can reproduce human pathophysiology and accelerate the search for lead compounds.
To this end, we have engineered an in vitro system to produce traumatic injury in human neurons derived from induced pluripotent stem cells. This system was built in-house to apply a repeatable stretch insult uniformly to each neuron at strains and strain rates typical of clinical TBI. We have demonstrated that we can produce clinically relevant pathology in a dose dependent manner and detect the therapeutic effect of neuroprotective agents. This creates an opportunity to rapidly and cheaply identify new drug candidates.
In addition to serving as a drug discovery tool, this system also enables a number of novel basic science experiments. It can compare pathology in isogenic populations of human neurons with a single genetic difference to test the influence of genetics on pathology. Also, we are creating a new model of axonal degeneration as a biomechanical phenomenon driven by elastic instability.
In another project, we are studying the effect of repeated mechanical insult on the formation and dissolution of stress granules to better understand the neurodegenerative consequences of repeated mild TBI. By combining insights from these experiments and incrementally increasing the complexity of our human in vitro TBI model, we intend to recreate the clinical challenge from the ground up to discover new mechanisms and treatments for this devastating disorder.
John is a Research Scientist with NorthShore University Health System. The laboratory that he directs is focused on the mechanisms and treatment of traumatic brain injury. After obtaining his PhD in Biomedical Engineering in 2010 from Duke University, focusing on cell mechanics and mechanotransduction, he worked as a Postdoctoral Research Scientist at Columbia University. He obtained his BE (Mechanical) degree from UCD in 2001.
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