The Jayadev Laboratory

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Our Neurogenetics laboratory studies the molecular mechanisms driving CNS and peripheral innate immune cellular phenotypes relevant to initiation or promotion of neurodegeneration.

Murine CNS and systemic inflammation models

Employing a cell-type specific transgenic murine model expressing a familial Alzheimer Disease Presenilin 2 mutation, we study the regulation of microglial and systemic immune responses to innate immune stimulation and stroke.   Microglia isolated from PSEN2 N141I mutation expressing mice have an exaggerated pro-inflammatory response, similar to those we have previously observed in PSEN2 knockout microglia, supporting a loss of function mechanism in innate immunity for PSEN2 mutations contributing to AD.

Patient derived innate immune studies in AD

In parallel, our laboratory has developed methods to investigate cell-autonomous and non-cell autonomous mechanisms in vitro with human neural and glial cells.  Using familial AD patient induced pluripotent stem cell lines or CRISPR/Cas9 gene edited embryonic stem cell lines we study the impact of genetic neurodegenerative disease associated microglia on inflammatory responses and neuronal health in vitro.   Complementing the microglial studies we are investigating the microRNA and transcriptomic alterations in peripheral innate immune cells isolated from patients carrying a familial AD (PSEN1, PSEN2, APP) gene mutation.

AD Genetic Risk in Patients and Their Families

Dr. Jayadev is PI of the UW Alzheimer Disease Research Center's Therapeutic Pipeline Project (TPP) Genetics project, a translational study investigating the genetic contribution to Alzheimer Disease using exome and genome sequencing.   The group is also studying clinical utility and patient impact of  exome sequencing for subjects with early onset AD or family histories of AD.  We are stratifying AD genetic risk, developing counseling methods for returning exome testing results to subjects and their families, and establishing collaborations to study functional variants in vitro.