Our group is interested in understanding the underlying pathophysiology of schizophrenia and autism by taking advantage of human genetics. One important area of research is the role of voltage gated calcium channels and calcium signaling in both of these disorders. Human genetic studies have identified a variety of genes encoding calcium channels and signaling proteins that confer susceptibility to schizophrenia. We have developed a variety of in vitro and in vivo models to study how these mutations alter the development and function of neurons and circuits. These include neurons derived from induced pluripotent stem cells, human brain organoids and mouse models. We have also generated a large collection of pharmacological agents that specifically modify the activity of calcium channels. We are using these tools to understand how calcium channels alter the properties of neurons and how this leads to neurodevelopmental disease and psychosis.
A second area of interest is understanding the underlying pathophysiology of neurodegenerative diseases. We are particularly interested in the role of immune cells and cytokines in Alzheimer’s disease and frontotemporal dementia. Our team has developed a broad set of reagents to study how microglial cells, astrocytes and lymphocytes affect neuronal function and survival in the context of neurodegenerative disease. These studies are helping us identify new drug targets and play a key role in the development of new therapeutics for these devastating disorders.