Research Interests

Research in my laboratory focuses on understanding the cellular and molecular mechanisms of synapse formation and refinement during development and in disease.  We use an arsenal of approaches, including development of new techniques, to address these questions both in vivo and in vitro. We have pioneered time-lapse imaging approaches to study protein transport before and during synapse formation and, most recently, synapse dynamics using a novel long-term imaging assay.

My laboratory is also one of only a few labs that study how “immune” molecules, such as MHCI and cytokines, regulate the initial establishment of cortical connections. We have found that MHCI molecules and interleukin-1 receptors are present at developing synapses, where they negatively regulate synapses.  Ongoing efforts aim to identify the molecular mechanisms that underlie these effects and identify the signaling molecules that act upstream of these synaptic immune molecules to cause synapse loss in development and in disease models.  Finally, we recently launched a new research direction into Alzheimer’s disease research focusing on the role for MHCI molecules in neurodegeneration. We have found that MHCI mediates Ab-induced synapse loss and cognitive deficits both in vivo and in vitro.

Since these immune molecules are implicated in several neurodevelopmental disorders, including autism and schizophrenia, MHCI molecules could mediate the effects of the environment on cortical connectivity both during normal development and in disease. Indeed, we have found that MHCI and cytokines mediate the effects of maternal infection in causing behavioral alterations in offspring.  In parallel to our basic research in neuroimmunology, we also work in translational neuroscience through leading a multi-disciplinary collaboration between eight groups at UC Davis, funded initially by a UC Davis RISE Pilot Center grant and transformed into an NIMH Conte Center, which was recently renewed. Through this center, we have identified proteins in female mice before pregnancy and following maternal immune activation that predict susceptibility and resilience to schizophrenia- and autism-related behavioral and neurochemical alterations in offspring. We are currently using this information to test biomarkers and new treatments to identify susceptible pregnancies and prevent the effects of maternal infection on brain development and behavior in offspring.

Graduate Program Affiliations

• Neuroscience Graduate Group