Stowe Lab

My overarching hypothesis is that the immune system – driven by an autoreactivity to CNS-derived antigens – plays a fundamental role in neuronal plasticity within the CNS. B cells, T cells, and natural killer (NK) T cells comprise the adaptive component of the immune system, with their interactions initiated by antigen recognition. In stroke, I hypothesize that long-term plasticity requires autoreactive T and B cell responses within the parenchyma, derived from lymphocyte populations sensitized to CNS antigens in the periphery. My preliminary data show that CD4 and CD8 T cells, as well as B cells, respond to specific immunogenic peptide sequences from neuronally-derived proteins that could potentially facilitate such processes as dendritic pruning, synaptogenesis, and axonal outgrowth in the ischemic brain. Although I use preclinical studies to investigate the mechanisms by which autoimmune responses affect post-stroke plasticity (e.g., protection from excitotoxicity, dendritic pruning), it is critical to concomitantly confirm and characterize these cells in humans. My clinical studies into the role of neuroinflammation during brain injury and repair has expanded beyond the field of ischemic stroke to also include subjects with amnestic mild cognitive impairment and pediatric patients on ventilator and hemodynamic support who experience stroke. The combination of preclinical and clinical studies reflects both my own training, which included a clinical postdoctoral fellowship, and my ongoing scientific philosophy that translational research will hasten the collective understanding of functional recovery during and following brain injury.

 

Our Research Today, few people can claim that stroke has not affected someone in their lives – a friend or family member, mother, or child. Within my family, both my grandmother and my aunt fought and survived stroke. But many are less fortunate, and again this year an estimated 800,000 individuals in the United States will suffer from a stroke.

Preclinical work in my lab focuses on neuroimmune mechanisms that contribute to neurovascular protection from ischemic injury. Exciting recent data from this research suggest a role for adaptive immunity to hypoxia after preconditioning that may be fundamental to neuroprotection following stroke, including a unique, anti-inflammatory B cell phenotype that is induced by prior stroke onset. This work, in a murine model of transient stroke, was the focus of a funded American Heart Association National Scientist Development Grant in 2014. Subsequent data on the mechanistic contribution of B cells to neuroprotection and neuronal plasticity after stroke laid the foundation for an R01/A1 funded in February 2015.

I have begun several collaborations to continue clinical research, in addition to the animal studies. Our funded clinical work investigates neuroinflammatory mechanisms in patients with mild cognitive impairment and Alzheimer’s disease. We also use functional imaging to understand plasticity changes during transcranial direct current stimulation-enhanced physical therapy in patients with prior stroke. Finally, we recently began research into the role of neuroinflammation during pediatric traumatic brain injury. I hope my interdisciplinary approach will result in a better understanding of mechanisms of recovery – and potentially new neurotherapeutics – for diseases that are the leading causes of long-term adult disability in the United States. This combined bench-to-bedside-to-bench approach has already led to the collection of preliminary data in humans that will inform the experimental design of mechanistic studies in mice.

Ann Stowe, PhD

Associate Professor

Departments of Neurology and Neuroscience

ann.stowe@uky.edu

Sarah Messmer, MPH

Scientist I

sarah.goodwin2@uky.edu

Jadwiga Turchan, PhD

Scientist I

turchan@uky.edu

Thomas Ujas

Graduate Student

t.ujas@uky.edu

Vanessa Torres

Graduate Student

vanessa.torres@utsouthwestern.edu

 

 

Katie Malone

Graduate Research Assistant

katie.malone101@uky.edu

Katherine Cotter

Graduate Research Assistant

katherine.cotter@uky.edu

For more information, contact the team behind the Center for Advanced Translational Stroke Science.

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