Forschung
AG Dr. Tuoc
Research group: Molecular Neurobiology
Our long-term interest is to investigate how the degenerated, injured brain and neurological disorders can recover. In the long run, we believe that understanding the intrinsic factors, including transcriptional and epigenetic programs, that instruct neuronal fates, will greatly help cell replacement therapy for neurodegenerative diseases by manipulating these factors and thus inducing neuronal generation.
Toward our goals, we are interested in elucidating the molecular features of the evolutionarily and clinically important basal progenitors (BPs), including the basal radial glia (bRGs) and intermediate progenitors (bIPs) in mammalian cortex. Recent findings in our laboratory have unraveled a number of key BP-enriched transcription, chromatin and epigenetic factors, which play essential roles in cortical neurogenesis. Furthermore, with the advent of next-generation sequencing (NGS), genes encoding for such BP-enriched factors in human neurological disorders have been discovered. Thus, the main aims of our research program are:
- To examine the epigenome and gene expression signatures of basal progenitors (BPs) and their subtypes in the developing cortex of evolutionarily distinct species, including rodent, non-human primate, and human.
- To identify novel factors and epigenetic programs that control BP genesis, cortical neurogenesis, and cortical expansion in evolution. The functions of above factors and their target genes will be elucidated partly by using spatiotemporal-specific (epi)genome editing tools such as Cre/LoxP based-, chemically/light inducible- systems in developing mouse cortex or in cerebral organoids.
- To establish protocols for the basal progenitor reprogramming from other cell sources for treatment of brain injury and Huntington's Disease in rodent models.
- To investigate the genetic mechanisms that cause cortical malformations in human and mouse. This would be achieved by applying our recently established fast protocol of microinjection-independent technique and genome editing to generate mouse models for human neurological disorders with mutated BP genes. The method would also be used for functional restoration of mutated genes in vivo.
Selected publication
1. Kerimoglu C, Pham L, Tonchev AB, Sakib MS, Xie Y, Sokpor G, Ulmke PA, Kaurani L, Abbas E, Nguyen H, Rosenbusch J, Michurina A, Capece V, Angelova M, Maricic N, Brand-Saberi B, Esgleas M, Albert M, Minkov R, Kovachev E, Teichmann U, Seong RH, Huttner WB, Nguyen HP, Stoykova A, Staiger JF, Fischer A, Tuoc T. H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion. Science advances. 2021
2. Ulmke PA, Sakib MS, Ditte P, Sokpor G, Kerimoglu C, Pham L, Xie Y, Mao X, Rosenbusch J, Teichmann U, Nguyen HP, Fischer A, Eichele G, Staiger JF, Tuoc T. Molecular Profiling Reveals Involvement of ESCO2 in Intermediate Progenitor Cell Maintenance in the Developing Mouse Cortex. Stem Cell Reports. 2021
3. Nguyen H, Kerimoglu C, Pirouz M, Pham L, Kiszka KA, Sokpor G, Sakib MS, Rosenbusch J, Teichmann U, Seong RH, Stoykova A, Fischer A, Staiger JF, Tuoc T. Epigenetic Regulation by BAF Complexes Limits Neural Stem Cell Proliferation by Suppressing Wnt Signaling in Late Embryonic Development. Stem Cell Reports. 2018
4. Narayanan R, Pirouz M, Kerimoglu C, Pham L, Wagener RJ, Kiszka KA, Rosenbusch J, Seong RH, Kessel M, Fischer A, Stoykova A, Staiger JF, Tuoc T. Loss of BAF (mSWI/SNF) Complexes Causes Global Transcriptional and Chromatin State Changes in Forebrain Development. Cell Rep. 2015
5. Tuoc T, Boretius S, Sansom SN, Pitulescu ME, Frahm J, Livesey FJ, Stoykova A. Chromatin Regulation by BAF170 Controls Cerebral Cortical Size and Thickness. Developmental Cell. 2013
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