Speaker: Pinar Ayata, PhD. Department Of Neuroscience , Icahn School of Medicine at Mount Sinai
Title: Specialized functions of microglia in health and disease
Abstract: Microglia, the resident macrophages of the brain, perform homeostatic functions that support the health and function of neurons. We recently identified cerebellar microglia (cbMg) as a subtype of microglia that specialize in the phagocytic clearance of apoptotic neurons while forebrain neurons specialize in the surveillance of neuronal activity. We uncovered an epigenetic mechanism underpinning their transcriptional signature, and showed that proper regulation of microglial functional state is crucial for normal brain function. Included in the cbMg signature is the reduced expression of myeloid lineage-determining transcription factor, Spi1. Recent human genetic studies found that lower level of SPI1 is a protective genetic trait in Alzheimer’s Disease (AD). Using a mouse model, we found that lower Spi1 levels boost the microglial response toward extracellular senile plaques, one of the major hallmarks of AD. This response is associated with alleviation of AD-associated pathology, providing the first in vivo mechanistic insight into the genetic association between lower SPI1 levels and reduced AD risk. Our studies collectively reveal answers to long- debated questions on the existence, regulatory mechanisms, and biological significance of microglial functional specification.
Bio: Dr. Ayata was born and raised in Turkey. After summer internships in German Cancer Research Center and Harvard Medical School she joined the laboratory of Nat Heintz at Rockefeller University as a PhD candidate. Her graduate work shed light on the interaction of 5- hydroxymethylcytosine modificiation and MeCP2 protein, and the pathophysiology of Rett syndrome. Her postdoctoral work in the laboratory of Anne Schaefer at Icahn School of Medicine at Mount Sinai elucidated epigenetic mechanisms that drive microglial functional specification necessary for normal brain function. Dr. Ayata’s ongoing work focuses on epigenetic mechanisms regulating microglial functional specification in Alzheimer’s disease. She is the recipient of Women and Science Graduate Fellowship, Rockefeller University Graduate Fellowship, NARSAD Young Investigator Award, and Robin Chemers Neustein Postdoctoral Award.