NEURODEVELOPMENTAL DISORDERS: Our group studies mechanisms that are responsible for neuronal specification, positioning and circuit formation during prenatal and postnatal brain development, and how these mechanisms are impaired in neurodevelopmental disorders (schizophrenia, epilepsy, autism).
The research focus of the laboratory is to understand how diversity of inhibitory neurons is established during brain development, how functional properties for subtypes of inhibitory neurons mature and how dysfunction of inhibitory neurons contributes to cognitive impairments in neurodevelopmental disorders. We address these questions from two complementary perspectives (see figure):
• In vivo: We unravel how signaling that specifies inhibitory neurons in vivo in mice and in humans during brain development is disrupted in neurodevelopmental disorders. By interfering with thus identified signaling pathways, we determine their contribution to neuronal function and integrity of neuronal networks.
• In vitro: We analyze in vitro specification of inhibitory neurons to measure changes in gene expression pattern that mediate neuronal differentiation in living human cells.
Importantly, in vivo and in vitro data are compared and complement each other in the quest to understand how disruption of inhibitory circuits during brain development contribute to neurodevelopmental disorders.
Barkas N.#, Petukhov V.#, Nikolaeva D., Lozinsky Y., Demharter S., Khodosevich K., Kharchenko PV. (2019). Joint analysis of heterogeneous single-cell RNA-seq dataset collections. Nat Methods, 2019 Jul 15. doi: 10.1038/s41592-019-0466-z.
Umezawa M., Onoda A., Korshunova K., Jensen A., Koponen I., Jensen K., Khodosevich K., Vogel U., Hougaard K. (2018). Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring. Part Fibre Toxicol, 15:36
Garcia-Gonzalez D.#, Khodosevich K.#, Watanabe Y., Rollenhagen A., Luebke J., Monyer H. (2017). Serotonergic Projections Govern Postnatal Neuroblast Migration. Neuron, 94(3): 534-49. Highlighted in Science Editor’s choice
Pfisterer U., Khodosevich K. (2017). Survival of immature neurons in the brain: neuron type-specific mechanisms. Cell Death Dis, 8, e2643
Farrow P.#, Khodosevich K.#, Sapir Y., Schulmann A., Stern-Bach Y., Monyer H., von Engelhardt J. (2015). CKAMPs: a novel family of putative AMPA receptor auxiliary subunits. Elife, 4: e09693
Khodosevich K., Jacobi E., Farrow P., Schulman A., Zhang L., Rusu A., Sprengel R., Monyer H., von Engelhardt J. (2014). Co-expressed auxiliary subunits exhibit distinct modulatory profiles on AMPA receptor function. Neuron, 83(3): 601-15. Video abstract; Article level metric = 68
Khodosevich K., Lazarini F., von Engelhardt J., Kaneko H., Lledo P. M., Monyer H. (2013). Connective tissue growth factor regulates interneuron survival and information processing in the olfactory bulb. Neuron, 79(6): 1136-1151. Highlighted in Neuron with a Preview