Terrance T. Kummer, M.D., Ph.D.
325 Biotechnology Bldg
traumatic brain injury, subarachnoid hemorrhage, microdialysis, MRI, diffusion tensor imaging
Understanding the mechanisms underlying neuronal trauma and degeneration during and following acute brain injury
Dr. Kummer’s research program is focused on understanding the mechanisms underlying neuronal trauma and degeneration during and following acute brain injury. Dr. Kummer carries out this research both in the laboratory, and in the Neurointensive Care Unit, where he is an attending. Brain injury is a leading cause of death and disability in the United States. Sudden brain injury usually takes one of two forms: traumatic or vascular. Traumatic brain injury occurs when the head receives a sudden external impact, possibly from an improvised explosive device, a car windshield, or even a barreling linebacker. Victims of such events may develop brain trauma near the site of impact, such as brain contusions, as well as ripple effects that damage the brain diffusely. Diffuse injury most importantly damages the axons that make up the brain’s wiring. Vascular brain injury takes the form of vascular blockage, causing strokes, and the far more deadly vascular rupture, which causes brain hemorrhages. Although an enlarging bleed causes obvious injury to adjacent brain, very little is known about the diffuse brain injury that likely underlies persistent coma and long-term cognitive and emotional impairment after brain hemorrhage. New results from Dr. Kummer’s group suggest that axon injury, so crucial in traumatic brain injury, also occurs during hemorrhagic brain injury. Dr. Kummer’s research is aimed at exploring this connection through the use of advanced brain imaging and neuromonitoring techniques available both in the laboratory and in the clinical setting.
One of the focuses of Dr. Kummer’s laboratory is on the development and application of cerebral microdialysis, which can serially sample biomarkers of pathology with excellent spatial resolution relative to a site of injury. Because the brain is highly inhomogeneous, this technique offers the opportunity to study biochemical processes that may affect brain tissues in different ways. It also allows direct delivery of therapeutics to specific brain regions, thereby laying the groundwork for intervention while providing a window onto the fundamental features of neuronal injury and degeneration. In collaboration with Dr. David Brody and Dr. Greg Zipfel, Dr. Kummer’s group is utilizing lab-based assays for measuring biomarkers of axonal injury from humans and animals, and experimental systems modeling both intracerebral hemorrhage and traumatic brain injury. Dr. Kummer also utilizes MRI techniques, namely diffusion tensor imaging, to reveal features of axonal injury in both animals and humans. Diffusion tensor imaging provides a ‘snapshot’ of axonal disruption across the entire brain, which complements the spatially limited (but highly temporally-resolved) information from cerebral microdialysis. Dr. Kummer’s group hopes, through the application of these technologies, to define a new class of brain injury—vascular traumatic brain injury—thereby connecting the large body of research into traumatic brain injury to a vascular disease process of particular relevance to our aging population. This framework should lead to new diagnostic and prognostic tests for victims of brain trauma, and help generate new targeted therapies.
Kummer TT, Misgeld T, Sanes JR (2006). Neuromuscular synaptogenesis: paradigm lost. Current Opinion in Neurobiology.16(1):74-82.
Misgeld T*,Kummer TT*, Lichtman JW, Sanes JR (2005). Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter. PNAS. 102: 11088-93.
*these authors contributed equally to this work
Kishi M,Kummer TT, Eglen SJ, Sanes JR (2005). LL5beta: a regulator of postsynaptic differentiation identified in a screen for synaptically enriched transcripts at the neuromuscular junction.J Cell Biol. 169(2):355-66.
Kummer TT, Misgeld T, Lichtman JW, Sanes JR (2004). Nerve-independent formation of a topologically complex postsynaptic apparatus.J Cell Biol. 164(7):1077-87.
Kummer TT, Nishimune H, Sanes JR (2002). Spotted substrates for focal presentation of proteins to cells. Biotechniques. 33(5):1018-20.
Last Updated: 12/16/2014 9:22:50 AM
Diffusion tensor imaging and correlated histology (left upper and lower panels, respectively) and schematic summary of injury to white matter regions (right) after subarachnoid hemorrhage