The human brain is one of the most complex objects in the universe. So it’s no surprise that biomedical researchers with both clinical and translational research interests have dedicated their careers to studying its development, function, and degeneration. The Duke University School of Medicine is a major center of cutting-edge neurological research, pulling in millions of dollars of NIH funding each year to elucidate the mechanisms underlying a wide range of diseases, from Parkinson’s Disease to stroke and traumatic brain injury. The Department of Neurology and its fourteen labs are making significant contributions to neurological research, advancing our understanding of the brain and how to treat disease.

The Kolls Lab

Led by Principal Investigator Dr. Bradley Jason Kolls, the Kolls Lab focuses on the central nervous system’s response to injury—particularly damage caused by stroke and brain hemorrhage. Leaning on Dr. Kolls’ MD/PhD training, the lab uses basic science and clinical approaches to study the brain. By examining patient data and using mouse models of brain injuries to examine the secondary effects of injuries and explore pathways to minimize damage in patients, Kolls and his team are well-situated to address patient recovery and mortality after brain injury. In their recent publication, the lab examined data from 66 hospitals on best practices for the reversal of oral anticoagulants, which are associated with increased risk for intracerebral hemorrhage (ICH). By implementing a system that introduced ICH patients with coagulant reversal agents as early as possible during care, the group successfully lowered the time to reversal in the median patient by roughly 40 minutes, significantly decreasing the likelihood of complications. The Kolls Lab is just one example of a lab within the Duke School of Medicine combining science and clinical data to improve patient outcomes.

In addition to the innovative work on traumatic brain injury and stroke, several labs within the Duke School of Medicine are dedicated to understanding and preventing neurodegeneration. The multidisciplinary nature of neurodegenerative disease led to the establishment of the Duke Center for Neurodegeneration and Neurotherapeutics (DCNN), which encompasses neurology, cell biology, molecular genetics, and microbiology. The DCNN strives to uncover intricate mechanisms underlying degenerative pathologies like Parkinson’s Disease and Alzheimer’s Disease and use these findings to facilitate therapy development, looping biomedical engineers into the inner workings of the DCNN. 

While the research interests of the many labs within the DCNN are incredibly diverse, these groups work together to shape our understanding of how the brain loses function.

The West Lab

For instance, the West Lab in the Department of Neurobiology, led by Dr. Andrew West, investigates a range of proteins that could contribute to Parkinson’s Disease or dementia. Specifically, the West Lab seeks to uncover how protein misfolding in the gut microbiome contributes to Parkinson’s. The protein alpha-synuclein, for example, often exhibits conformational changes early in neurodegenerative disease, and many patients report alteration in their gastrointestinal function well before a diagnosis. Interestingly, the West Lab has identified cells that function similarly to neurons in the gut. Called enteroendocrine cells, these express alpha-synuclein while contacting external toxins and pathogens in addition to the central nervous system. This external connection to alpha-synuclein misfolding and its potential transfer to the brain is the subject of current experimentation in the West Lab.

Above: A model of the proposed pipeline of alpha-synuclein misfolding from the gut to the brain. Image courtesy of the West Lab.  

The Soderling Lab

Another lab in the DCNN, the Soderling Lab in the Department of Cell Biology, studies how complex neural circuits are controlled by protein network disruptions arising from genetic mutations. Dr. Scott Soderling and other members of the lab have employed unique methods to manipulate proteins that have significant implications for protein engineering and therapeutic development. In its recent preprint, the lab used a template-guided protein design framework called Raygun to miniaturize proteins while maintaining their structure and general function. Raygun allowed the team to introduce significant changes in genetic sequences while maintaining the integrity of functional sites. This groundbreaking work conducted by DCCN faculty is critical to understanding mechanisms driving neurodegeneration and paving the way for future treatments. 

The neurological research happening at Duke is both innovative and highly diverse. The Department of Neurology and the DCNN are home to a wide range of labs and teams attempting to combat key neurodegeneration and brain disease more broadly. For undergraduates interested in research, the Department of Neurology and the DCNN represent incredible opportunities to get involved in several distinct fields. Further, the proximity of these labs to the Duke Hospital fosters a sense of collaboration between clinicians and researchers, making the effects of these labs all the more impactful right here on campus and beyond.