Models of Alzheimers disease
There is significant evidence for a central role of inflammation in the development of Alzheimer’s disease (AD). Epidemiological studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD in healthy aging populations. As NSAIDs inhibit the enzymatic activity of the inflammatory cyclooxygenases COX-1 and COX-2, these findings suggest that downstream prostaglandin signaling pathways function in the pre-clinical development of AD.
Current areas of study in the lab focus on identifying cellular and molecular mechanisms of action of downstream prostaglandin pathways using in vitro and in vivo transgenic models of neurological disease.
Models of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease, characterized by the progressive loss of motor neurons in the spinal cord and motor cortex. Pathologic findings in ALS show marked inflammation in the spinal cord and brain, with activation of glial cells, induction of expression of pro-inflammatory enzymes and cytokines, and increased oxidative stress.
Although the precise molecular trigger of ALS is unknown, this chronic inflammatory state accelerates disease progression, leading to sustained loss of motor neurons. Research in the laboratory has been focused on understanding the nature of the inflammatory process in ALS as a potential target to reduce or halt the progression of this disease.
Mechanisms of injury in cerebral ischemia
Inhibition of COX-2 in models of cerebral ischemia significantly reduces stroke injury, suggesting that downstream prostaglandin signaling pathways play major roles in stroke evolution and outcome. Studies in the lab are focusing on identifying cell-specific mechanisms of action of prostaglandin signaling in the acute and recovery phases of stroke, focusing on endogenous neuronal, inflammatory, and vascular mechanisms of action.
Models of Parkinson's Disease
PD neuropathology is characterized by the accumulation of intracellular a-synuclein, loss of dopaminergic neurons, and a significant inflammatory response. The inflammatory response involves secretion of soluble factors such as cytokines, chemokines, and reactive oxygen species that can induce neuronal and synaptic injury. Controlled inflammatory responses are generally beneficial for the host and are important in defense against pathogens.
However, dysregulated neuroinflammatory responses, as occur in PD lead to neuronal injury. Studies in the lab are focusing on the role of COX-2/prostaglandin neuroinflammatory responses in models of PD.