University of Kentucky
101 Sanders-Brown Bldg
800 S. Limestone Street
Lexington, KY 40536
Anatomy and Neurobiology, Kentucky Neuroscience Institute and Sanders-Brown Center on Aging
Signal transduction, glia-neuron interactions, neuroinflammation, drug discovery for neurodegenerative disorders
Research in the Van Eldik lab aims to elucidate the mechanisms by which abnormal activation of glia in the brain, especially astrocytes and microglia, leads to damage of the neurons and progressive neurodegeneration in diseases like Alzheimer's disease (AD) and traumatic brain injury (TBI). The overall goal is to utilize knowledge of potentially "druggable" pathways to develop new therapeutics. The normal role of the glia is to cooperate with the neurons to keep the brain operating smoothly. When an injury or change in the brain occurs, the glial mount a beneficial inflammation response to fight off the insult and restore the brain to its proper functioning. While a controlled inflammatory response is an important element in protecting the brain, this beneficial process sometimes gets out of balance and the inflammation becomes too strong or does not shut off on schedule. In neurodegenerative diseases, the glia are over-activated, producing detrimental inflammatory molecules called proinflammatory cytokines that can contribute to nerve cell death and accelerate the progression of the disease. Although neuroinflammation appears to play a pivotal role in the development and progression of neurodegeneration, the molecular mechanisms underlying the process and approaches to downregulate the neuroinflammation have received little attention. This raises the logical question of whether drugs can be developed to selectively target cytokine up-regulation in glia,with the hope that such drugs would slow down or perhaps even prevent disease progression.
Projects in the Van Eldik lab are focused on identification of signal transduction pathways that mediate the neuroinflammatory responses of activated glia and exploration of how aberrant glial-neuronal interactions contribute to or influence neurodegenerative processes. In collaborative research with medicinal chemistry and integrative pharmacology colleagues, we have extended this knowledge of pathophysiology progression to drug discovery efforts that have yielded novel small molecules that are candidates for drug development as well as tools to explore the potential of improved neurologic outcomes by restoration of activated glia back towards homeostasis.
P30 AG028383 Van Eldik (PI) 7/01/06 – 6/30/16
Alzheimer’s Disease Core Center
The major goal of this center is to build on the existing broad-based AD Program to gain an understanding of pathogenic mechanisms in AD with the eventual goal of prevention and treatment of the disease.
Kentucky Spinal Cord & Head Injury Research Trust 12-20A Van Eldik (PI) 1/15/13 – 1/14/16
Novel Therapeutics for Traumatic Brain Injury: Targeting the Acute Cytokine Surge
Goal: test dose dependence and define optimal therapeutic efficacy window of anti-cytokine compounds in an animal model of traumatic brain injury.
R01 NS093920 Van Eldik (PI) 5/01/15 – 4/30/20
Microglia Responses to CNS Injury: Targeting p38 MAPK Signaling
This project will test the hypothesis that suppression of p38a signaling in appropriate therapeutic windows and appropriate cell types after traumatic brain injury can lead to selective, beneficial outcomes.
U01 AG050636 Van Eldik (PI) 9/01/15 – 4/30/18
Preclinical Development of a Selective Suppressor of Neuroinflammation for MCI/AD
This grant supports preclinical IND-enabling ADME/tox studies to bring to IND status a novel experimental therapeutic for development as an oral formulation for the future treatment of MCI/AD.