Alexandra (Sasha) Mikhailova

Research Description

Sasha’s research aims to understand the mechanisms of neuroimmune signaling (MHC Class I) at cortical synapses. MHCI is generally assumed to negatively regulate the formation and function of synapses postsynaptically, however it has also been found in axons and at the pre-synaptic terminal. A role in these compartments has yet to be described. To understand the function of MHCI at the presynaptic compartment, Sasha employs genetic tools to knock down or overexpress MHCI in neurons in vitro to evaluate  its effects on synapse density and dynamics using long-term live imaging. Her goal is to determine whether, and how, MHCI molecules in presynaptic cortical neurons regulate the density of synapses formed onto their targets. Using a novel co-culture system, she has discovered that MHCI levels in presynaptic neurons negatively regulate the number of synapses they form onto their targets. She will determine whether activity regulates the density and dynamics of synapses a cell makes onto its targets, as well as whether the presynaptic effects of MHCI on synapse density are activity-dependent. Results from this project will provide new information about the protein dynamics underlying synapse formation and elimination in early developing neural networks and will reveal novel cellular mechanisms mediating the effects of presynaptic MHCI in regulating synapse formation. Sasha’s findings may thereby provide insight into how novel therapies could be developed to alter MHCI signaling in the brain in the future to ameliorate neuroimmune- based disorders.