Central nervous system (CNS) metabolism and neuronal excitability are interdependent, and so CNS
metabolism is the biochemical basis of cognition, memory, and behavior. Dysregulation of CNS is implicated in
numerous disorders, including Alzheimer’s Disease, epilepsy, Parkinson’s disease, and brain injury, but the
mechanistic connections between CNS metabolism and disease are poorly understood. The University of
Kentucky (UK) College of Medicine has made significant investments over the last few years in investigators
with metabolic and metabolomics expertise and instrumentation to support their research efforts, which has
enhanced existing strengths in neuroscience, cancer, cardiovascular, and diabetes and obesity research.
Thus, UK proposes to establish a unique multidisciplinary Center of Biomedical Research Excellence (COBRE)
on CNS Metabolism (CNS-Met) as a strategically designed, sustainable framework that promotes leading-edge
research focused on the role of metabolic mediators of brain function and disease. The proposed
interdisciplinary center leverages highly specialized expertise in glucose biology, neuronal signaling,
mitochondrial metabolism, systems neuroscience, and data sciences as well as the presence of advanced
metabolomics and imaging capabilities to create an integrated research framework focused on CNS
metabolism. The overarching goals are to strengthen UK’s neuroscience research enterprise by providing a
thematically focused and sustainable multidisciplinary infrastructure dedicated to defining the contribution of
metabolism to CNS function and neurological diseases and to use this novel platform to develop promising and
highly-skilled, early-stage investigators in an exciting and impactful area of CNS research. To accomplish
these goals, we will meet four specific aims: (1) Develop a critical mass of funded investigators with research
programs directly related to the COBRE’s unifying theme; (2) provide strong team-based mentoring combining
basic and clinical expertise; (3) recruit new investigators to the COBRE in multidisciplinary areas of neurologic
dysfunction through pilot project grant and recruitment of junior Research Project Leaders; and (4) create
synergy among research projects via critical links to strong research centers and core facilities at UK, including
existing COBREs. Emerging synergies will be developed through three research projects, an Administrative
Core, a critical research core in Metabolomics, all linked by strong biostatistics/bioinformatics support, all of
which are critical to the proposed studies and will contribute to the development of institutional resources. The
scientific focus of the three research projects are brain metabolism interactions with neurological disease,
spanning basic and translational perspectives. This concentration of multidisciplinary expertise focused on
widely recognized yet understudied metabolic mechanisms of neurological diseases promises significant new
understandings of CNS metabolism overall. The CNS-Met will create a critical mass of skilled scientists who
are well equipped to lead a sustainable research center focused on CNS metabolism into the future.