Hisashi Umemori, MD, PhD

Professor of Neurology, Harvard Medical School.

Research Focus
Synaptic circuit development and function.
Brief Research Description
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. Dr. Umemori's lab is therefore interested in the molecules and mechanisms by which specific and functional synaptic connections are established in the brain, and are applying their findings to the prevention and treatment of neurological/psychiatric disorders. They use molecular & cellular biological, mouse genetics, biochemical, histological, physiological, behavioral, and imaging techniques. Through their work they aim to understand the principle of mammalian brain wiring and how the functional brain is built. Specifically, they 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). They 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. Their projects will molecularly delineate how specific and functional synaptic connections are established in vivo to understand the process of fundamental wiring of the brain. The knowledge obtained will be applied to the prevention or treatment of neurological and psychiatric disorders associated with abnormal synapse formation, such as autism, schizophrenia, and epilepsy.
Key Publications (PMCIDs)

Female-specific synaptic dysfunction and cognitive impairment in a mouse model of PCDH19 disorder.
Hoshina N, Johnson-Venkatesh EM, Hoshina M, Umemori H.
Science 2021; 372(6539): eaaz3893. PMID: 33859005.

An activity-dependent determinant of synapse elimination in the mammalian brain.
Yasuda M, Nagappan-Chettiar S, Johnson-Venkatesh EM, Umemori H.
Neuron 2021; 109(8): 1333-1349. PMID: 33770504.

Retrograde fibroblast growth factor 22 (FGF22) signaling regulates insulin-like growth factor 2 (IGF2) expression for activity-dependent synapse stabilization in the mammalian brain.
Terauchi A, Johnson-Venkatesh EM, Bullock B, Lehtinen MK, Umemori H.
Elife 2016;5:e12151. PMCID: PMC4868541

Synapse maturation by activity-dependent ectodomain shedding of SIRPα.
Toth AB, Terauchi A, Zhang LY, Johnson-Venkatesh EM, Larsen DJ, Sutton MA, & Umemori H.
Nature Neuroscience 2013; 16, 1417-1425. PMCID: PMC3820962.

Distinct FGFs promote differentiation of excitatory and inhibitory synapses
Terauchi A, Johnson-Venkatesh EM, Toth AB, Javed D, Sutton MA, & Umemori H.
Nature 2010; 465, 783-787. PMCID: PMC4137042.