The Molecular & Cellular Neuroscience (MCN) Program's Seminar Series
Description
"The Dopaminergic Synaptic Organizers"
Speaker Bio
Hisashi Umemori’s initial training was as M.D. (University of Tokyo), but early in his clinical career, he decided to devote himself to understanding the basis of the neurological diseases that he was unable to treat properly. At the University of Tokyo, he analyzed the molecular mechanisms underlying myelination (Ph.D. work) and synaptic plasticity. These studies kindled his interest in how synapses form in the brain - As a postdoctoral fellow in Joshua Sanes’ lab at Washington University and Harvard University, Dr. Umemori started studying synapse formation. He joined the faculty of the University of Michigan in 2006 and returned to Harvard University and joined the F.M. Kirby Neurobiology Center at Boston Children's Hospital in 2013, deciphering the cellular and molecular mechanisms underlying the establishment of specific and functional synaptic connections in the brain.
Dr. Umemori received awards from Klingenstein Fellowship, Robert H. Ebert Clinical Scholar, Mallinckrodt Foundation, March of Dimes Foundation, and Whitehall Foundation.
Additional Info
In the brain, information processing occurs at synapses, and defects in synapse formation underlie many neurological and psychiatric diseases; thus, precise organization of synapses is critical for proper functioning of the brain. We are therefore interested in the molecules and mechanisms by which specific and functional synaptic connections are established in the brain, and are applying our findings to the prevention and treatment of disorders associated with abnormal synapse formation, such as autism, schizophrenia, and epilepsy. We use molecular & cellular biological, mouse genetics, biochemical, histological, physiological, behavioral, and imaging techniques.
Specifically, we identify molecules and mechanisms crucial for synapse formation, focusing on two critical steps during synapse development: 1) differentiation of specific synapses (such as excitatory vs. inhibitory synapses) and 2) activity-dependent refinement of functional synapses (i.e., stabilization of active synapses and elimination of inactive synapses). We establish in vitro and in vivo systems to investigate these steps, analyze the underlying mechanisms, and identify critical determinants for the establishment of appropriate synaptic circuits in the mammalian brain. For example, we have performed an unbiased search (biochemical purification) and identified that FGFs are critical for synaptic differentiation in the mammalian brain (Cell 2004) and showed that three molecules (FGF, laminin, collagen) act sequentially to organize neuromuscular junctions in vivo (Cell 2007). Remarkably, we have identified FGF22 and FGF7 as molecules that promote the organization of excitatory and inhibitory synapses, respectively, in the hippocampus in vivo, and showed that FGF22-deficient mice are resistant to epileptic seizures, and FGF7-deficient mice are prone to them (Nature 2010). Furthermore, we have established a genetic system in which neural activity can be conditionally controlled and demonstrated how functional memory circuits are built in vivo (Neuron 2011). We have also identified signal regulatory proteins (SIRPs) as synaptogenic molecules (JBC 2008) that are involved in the activity-dependent step of synapse maturation (Nature Neuroscience 2013).
Through our work, we aim to understand the principle of mammalian brain wiring and how the functional brain is built. The knowledge obtained will be applied to prevent or treat neurological and psychiatric disorders.