Titles
- Professor
- Vice Chair Research, Dept of Neurology.
Linked information
Departments
Lab Medicine and Pathology, Medical Genetics, Medicine
Roles
BMHA Training Faculty, HALO Faculty
Dr. Jayadev is a neurogeneticist and translational neuroscientist at the University of Washington whose career has focused on the clinical features and biological mechanisms of age-related neurodegenerative disease.
Her laboratory has studied microglial biology and neuroinflammatory mechanisms contributing to Alzheimer’s disease (AD) and related disease pathogenesis for over 16 years, and published one of the early iPSC differentiation to microglia papers exploring differentiated microglia phenotype if driven down a primitive versus definitive developmental path. Microglia are intrinsically diverse and it is known they likely contribute to “inflammaging”, changes that may induce a less supportive neural environment. To understand whether these different microglial states are present in normal aging, show any sex differences, or changes in the presence of AD pathology, we developed a microglial enrichment strategy prior to performing single nucleus RNA-seq (Prater et al., Nature Aging, 2023). We have performed similar studies in younger (30-50-s) control brains and can now demonstrate biological pathways (defined transcriptomically) that change with normal aging.
In collaboration with Dr. Jessica Young and Elizabeth Blue they are exploring the effect of aggregate endolysosomal polygenic risk on neural cell health using both stem models and matched donor autopsy tissue. They have developed an endolysosomal pathway polygenic risk score (ePRS) that they found predicted incident Alzheimer Dsiease. However they found that when we examined the association of the ePRS in our multiple cohorts, high ePRS is associated with earlier age of death, but only in those considered “controls” pathologically. In other words, while endolysosomal dysfunction is thought to contribute to normal aging, our finding of genetic loci harboring endolysosomal genes correlating to age of death may provide additional mechanistic clues about how the process leading to cell aging of injury is regulated. Another exciting project they are developing investigates how aggregate polygenic risk in endolysosomal network genes drives cell-type-specific dysfunction across the aging brain through epigenetic mechanisms, in collaboration with Dr. Daniel Zemke, at UCSD. She is collaborating with Dr. David Marcinek on his innovative interventional trial regarding the use of elamipretide (ELAM), to counter the metabolic deficits associated with aging. They have successfully completed a pilot phase and hope to continue working with his team as the project develops.
As a clinician-scientist, she directs the UW Neurogenetics Clinic and the UW Huntington Disease Center of Excellence, and follows presymptomatic and symptomatic individuals with familial early- and late-onset AD. She serves as UW site PI for the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), and as Associate Director and Clinical Core Leader of the UW Alzheimer’s Disease Research Center (ADRC), where she oversees clinical phenotyping, diagnosis, and recruitment for the Center’s aging cohort. She is Vice Chair for Research in the Department of Neurology, where she supports research infrastructure and training across the department.
Her research has been continuously funded by the NIA since 2011. She has mentored numerous graduate students, postdoctoral fellows, and junior faculty, and served the broader aging and neurodegeneration research community as an editorial board member for Glia, Associate Editor for Neurology Genetics, a longtime NIA study section member and former chair (NIA-A AGCD-4), and a member of the AAN Science Committee. She is currently faculty with M3D and serves on a number of graduate student committees.
