Khodosevich Group

We aim to address the key questions for our understanding of brain function “how such complex organ as the brain is build up during development?” and “what goes wrong in neurodevelopmental disorders?”.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  • Response to genetic and environmental stimuli determines the vulnerability of neurons to neurodevelopmental disorders.
  • The vulnerability of neurons is highly dependent on developmental period; thus, there are critical periods of development, when different types of neurons are particularly vulnerable, or particularly resilient, and these periods differ for different neuronal types

Read papers: Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific mannerIdentification of Vulnerable Interneuron Subtypes in 15q13.3 Microdeletion Syndrome Using Single-Cell Transcriptomics

  • Neuronal types, circuits and gene expression at single-cell resolution that contribute to epilepsy and schizophrenia in human brain.

Read papers: Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis & Selective vulnerability of supragranular layer neurons in schizophrenia

  • Identification of a pivotal metabolic gene to pair energy production and energy demand in fast-spiking interneurons (the key neurons in neurodevelopmental disorders)
  • Specific metabolism of fast-spiking interneurons programs their neuronal maturation, and when impaired leads to neuropsychiatric phenotype

Read paper: Complex IV subunit isoform COX6A2 protects fast‐spiking interneurons from oxidative stress and supports their function

 

 

 

 

 

 

 

 

 

Normal brain development

  • Neuronal specification in normal brain.
  • Maturation of cortical interneurons.

Neurodevelopmental disorders

  • Epilepsy:
    • Mechanisms of epileptogenesis in human tissue and animal models.
    • Functional characterization of human neurons in epileptic tissue
  • Schizophrenia:
    • Effects of environmental factors, such as maternal viral infections, inflammation, and pre-term birth on fetal brain development and postnatal brain maturation.
    • Effects of schizophrenia-associated genetic mutations on fetal brain development and postnatal brain maturation.
    • Formation of neuronal circuits underlying schizophrenia.
    • Metabolic impairment in schizophrenia.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Selected publications

Experimental papers

Batiuk M#, Tyler T#, Dragicevic K, Mei S, Rydbirk R, Petukhov V, Deviatiiarov R, Sedmak D, Frank E, Feher V, Habek N, Hu Q, Igolkina A, Roszik L, Pfisterer U, Garcia-Gonzalez D, Petanjek Z, Adorjan I, Kharchenko P, Khodosevich K (2022) Upper cortical layer–driven network impairment in schizophrenia. Sci Adv 8, eabn8367

Malwade S, Gasthaus J, Bellardita C, Andelic M, Moric B, Korshunova I, Kiehn O, Vasistha NA, Khodosevich K. (2022) Identification of vulnerable interneuron subtypes in 15q13.3 microdeletion syndrome using single-cell transcriptomics. Biol Psychiatry, 91(8): 727-739

Pfisterer #, Demharter S.#, Petukhov V.#, Meichsner J.#, Thompson J., Batiuk M., Asenjo Martinez A., Vasistha N., Thakur A., Mikkelsen J., Adorjan I., Pinborg L., Pers T., von Engelhardt J., Kharchenko P., Khodosevich K. (2020) Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. Nat Commun, 11(1):1-19

Vasistha N.#, Pardo-Navarro M.#, Gasthaus J., Weijers D., Müller M., García-González D., Malwade S., Korshunova I., Pfisterer U., von Engelhardt J., Hougaard K., Khodosevich K. (2019) Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific mannerMol Psychiatry, 10.1038/s41380-019-0539-5

Sanz Morello B., Pfisterer U., Hansen N., Demharter S., Thakur A., Fujii K., Levitskiy S., Montalant A., Korshunova I., Mammen P., Kamenski P., Noguchi S., Aldana Garcia B., Hougaard K., Perrier J., Khodosevich K. (2020) Unique isoform in oxidative phosphorylation machinery supports the function of fast-spiking neurons. EMBO J, 39(18):e105759

Computational papers

Petukhov V#, Igolkina A#, Rydbirk R, Mei S, Christoffersen L, Khodosevich K#, Kharchenko P# (2022). Case-control analysis of single-cell RNA-seq studies. bioRxiv 2022.03.15.484475.

Petukhov V, Xu R, Soldatov RA, Cadinu P, Khodosevich K, Moffitt J, Kharchenko P. (2021) Cell segmentation in imaging-based spatial transcriptomics. Nat Biotech, 40(3): 345-354

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.

Reviews & Perspectives

Khodosevich K, Dragicevic K, Howes O. (2023) Drug targeting in psychiatric disorders – how to overcome the loss in translation? Nat Rev Drug Discovery, s41573-023-00847-7

Khodosevich K, Sellgren CM. (2023) Neurodevelopmental disorders—high-resolution rethinking of disease modeling. Mol Psychiatry 28(1):34-43

View all publications

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

In the media

Forskere på KU afslører de specifikke neuron-fejl bag skizofreni

19.10.2022 by Ingeniøren (story also brought in Dagens Medicin and on bric.ku.dk)

Et bestemt gen kobles til autisme, ADHD, skizofreni og andre diagnoser

02.11.2021 by Videnskab.dk

New video: How to build a healthy brain.

Study identifies brain cells most affected by epilepsy and new targets for their treatment

07.10.2020 by Faculty of Health and Medical Sciences

BRIC researchers discover role of metabolism gene in brain dysfunction

04.08.2020 by BRIC

How are psychiatric disorders linked to infections during pregnancy?

30.10.2019 by Faculty of Health and Medical Sciences

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