The Role of Complement in Brain Injury
Jeanne Paz, PhD
Associate Investigator, Gladstone Institutes
Associate Professor of Neurology
Uniersity of California San Francisco (UCSF), CA
Traumatic brain injury (TBI) is a leading cause of disability in children and adults. TBI affects 69 million people worldwide yearly and can lead to cognitive dysfunction, difficulty with sensory processing, sleep disruption, and epilepsy. Although TBI acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. Our work aims to understand where, when, and how secondary injuries develop, which is crucial for preventing or disability following TBI. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system. Increased C1q expression colocalized with neuron loss and chronic inflammation and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities. Dr. Paz will present the ongoing work in her laboratory that aims to identify the cellular and circuit mechanisms behind complement-mediated neural plasticity after TBI and its role in post-traumatic epileptogenesis.
Jeanne Paz obtained a PhD from University Pierre and Marie Curie in Paris, in the lab of Dr. Jacques Glowinski (who earlier trained with Julius Axelrod at the National Institutes of Health (NIH)). During that time, Jeanne performed the deepest intracellular recordings ever done in rats and discovered the role of basal ganglia in controlling thalamocortical function during seizures. Jeanne did her postdoctoral work next in the Huguenard and Deisseroth labs, where she developed the first closed-loop optogenetic approach to control cells in real time during automatically detected seizures. This work led to the discovery of the key role that the thalamus plays after stroke. Since 2014, Jeanne has been directing a lab at University of California, San Francisco (UCSF) and the Gladstone Institutes, where she studies the role of thalamocortical circuits in health and disease. She is a recipient of multiple awards including the international Michael prize for best research in epilepsy, and the Vilcek Prize.
This seminar series aims to create and sustain collaborations between clinicians and researchers at Weill Cornell Medicine who have interests in brain injury. To join the listserv please send an email to sut2006 at med dot cornell dot edu.
Sudhin A. Shah, PhD
Assistant Professor of Neuroscience in Radiology
Brain Health Imaging Institute
Weill Cornell Medicine
sut2006 at med dot cornell dot edu
Tracy Butler, MD
Associate Professor of Neurology in Radiology
Brain Health Imaging Institute
Weill Cornell Medicine
tab2006 at med dot cornell dot edu