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Effects of early life adversity on neural connectivity and behavior in mice

Arie Kaffman’s laboratory uses mouse models to investigate the cellular and molecular mechanisms through which early-life adversity disrupts brain development and shapes cognitive and emotional outcomes across the lifespan. The central focus of the lab is to understand how adversity-induced alterations in microglial function—the brain’s resident immune cells—during sensitive developmental periods lead to persistent changes in neural connectivity, cognition, and behavior. The Kaffman lab has demonstrated that abnormal microglia-mediated synaptic pruning during the second and third postnatal weeks is a key causal mechanism underlying impaired synaptic maturation and hippocampal-dependent cognitive deficits later in life. To address these questions, the lab integrates a wide range of experimental approaches, including behavioral assays, genomic and proteomic analyses, DiOlistic labeling, high-resolution confocal microscopy, flow cytometry, ex vivo phagocytic assays, and chemogenetic manipulations. In parallel, the lab employs human neuroimaging techniques, including resting-state functional MRI and high-resolution diffusion MRI. These imaging approaches enable direct cross-species comparisons and provide a translational framework for linking developmental disruptions in microglia-mediated synaptic pruning to alterations in brain circuitry and behavior in humans.

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Biography

As an undergraduate at UC Berkeley, Kaffman was a first author on a Science paper, an achievement that sparked a lasting fascination with the elegance of scientific discovery. He completed his MD/PhD at UCSF in Erin O’Shea’s laboratory, studying how phosphorylation regulates the nuclear import and export of transcription factors in yeast. In 2001, he entered the Neuroscience Research Training Program at Yale and established his laboratory in the Department of Psychiatry in 2006. Kaffman is married, has a son and daughter in their twenties, and believes the best pizza in New Haven is Sbarro train station.