Yongsoo Park Lab

NeuroBiology

Modeling neurological disorders

RESEARCH

<p>Our research is for modeling neurological disorders using reconstitution and stem cell-based approach with a focus on vesicle fusion and calcium signaling.</p>
<p>1) Modeling neurodevelopmental disorders using iPSC-derived neurons and brain organoids.<br />
2) Extracellular vesicle (EV) biomarkers and EV-mediated inflammation in neurological disorders.<br />
3) Lipid dysregulation in neurodegenerative diseases.<br />
4) New paradigm of RIBOMONE in physiology and pathology.</p>

Our research is for modeling neurological disorders using reconstitution and stem cell-based approach with a focus on vesicle fusion and calcium signaling.

1) Modeling neurodevelopmental disorders using iPSC-derived neurons and brain organoids.
2) Extracellular vesicle (EV) biomarkers and EV-mediated inflammation in neurological disorders.
3) Lipid dysregulation in neurodegenerative diseases.
4) New paradigm of RIBOMONE in physiology and pathology.

<p>Although microRNA (miRNA) regulates gene expression inside the cell where they are transcribed, extracellular miRNA has been recently discovered outside the cells, proposing that miRNA might be released to participate in cell-to-cell communication (Front Endocrinol. 2017).</p>
<p>My group first reported the active exocytosis of miRNAs independently of exosomes in response to neuronal stimulation.</p>
<p>We propose a new function of non-coding RNAs named (‘ribomone’ = ribonucleotide + hormone), and suggest that miRNAs may function as hormones; i.e., miRNA is stored in vesicles and released by vesicle fusion in response to stimulation, thereby contributing to cell-to-cell communication.</p>

Although microRNA (miRNA) regulates gene expression inside the cell where they are transcribed, extracellular miRNA has been recently discovered outside the cells, proposing that miRNA might be released to participate in cell-to-cell communication (Front Endocrinol. 2017).

My group first reported the active exocytosis of miRNAs independently of exosomes in response to neuronal stimulation.

We propose a new function of non-coding RNAs named (‘ribomone’ = ribonucleotide + hormone), and suggest that miRNAs may function as hormones; i.e., miRNA is stored in vesicles and released by vesicle fusion in response to stimulation, thereby contributing to cell-to-cell communication.

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Lipid metabolism plays a crucial role in maintaining neuronal function, and alterations in lipid composition, including the reduction of phosphatidylinositol 4,5-bisphosphate (PIP2), have been implicated in neurodegenerative disorders. PIP2 is a key regulator of cell signaling and membrane trafficking, and its dysregulation is associated with neuronal dysfunction. Our research was the first to demonstrate that PIP2 functions as an electrostatic catalyst for vesicle fusion by lowering the hydration energy barrier (ACS Nano, 2024; Science Advances, 2025). We propose a paradigm shift in which PIP2 is recognized as a lipid catalyst for vesicle fusion, expanding our understanding of the molecular mechanisms governing neurotransmitter release.

Additionally, our findings indicate that cholesterol is essential for Ca²⁺-dependent vesicle fusion by enhancing membrane bending and deformation (Advanced Science, 2023). Using reconstitution assays with native vesicles, we identified a novel mechanism by which cholesterol facilitates vesicle fusion. Unlike synthetic liposomes, native vesicles are required for the reconstitution of physiological vesicle fusion. Our studies suggest that both PIP2 and cholesterol are essential for vesicle fusion, emphasizing that lipids can function as biological catalysts rather than passive structural components.

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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits and frequent comorbidities such as epilepsy. Genetic studies indicate that ASD-associated risk variants converge on calcium signaling pathways and vesicle fusion.

We employ functional assays such as single-cell calcium imaging, whole-cell patch-clamp electrophysiology, and microelectrode array (MEA) recordings to characterize these pathophysiological changes.

Team

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Yongsoo Park, Ph.D.

Senior Scientist / Associate Professor

Member, EMBO Young Investigator Programme (YIP) as an EMBO Installation Grantee, 2016-2019.

LinkedIn / ResearchGate Google Scholar


 

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Kyung Chul Shin, Ph.D.

Postdoctoral Fellow


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Gowher Ali, Ph.D.

Postdoctoral Fellow


 

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Houda Yasmine Ali Moussa

Research Associate


 

Rawan Hussam Albatarni

Graduate student

Alumni

Yelda Birinci Post-doc

Alican Gümürdü Graduate Student

Obadah Al Bahra Graduate Student

Ramazan Yildiz Graduate Student

Selected Publications

#, Corresponding author

Full lists in PubMed.

  1. Ali Moussa HY, Shin KC, Park Y#. Ca2+/calmodulin and protein kinase C (PKC) reverse the vesicle fusion arrest by unmasking PIP2. Science Advances. 2025 Feb 28;11(9):eadr9859.
  2. Park Y#. Fluorescence anisotropy for monitoring cis- and trans-membrane interactions of synaptotagmin-1. Methods Mol Biol. 2025;2887:175-182.
  3. Ali Moussa HY, Shin KC, de la Fuente A, Bensmail I, Abdesselem HB, Ponraj J, Mansour S, Al-Shaban FA, Stanton LW, Abdulla SA, Park Y#. Proteomics analysis of extracellular vesicles for biomarkers of autism spectrum disorder. Front. Mol. Biosci. 2024;11:1467398.
  4. Shin KC, Ali Moussa HY, Park Y#. Cholesterol imbalance and neurotransmission defects in neurodegeneration. Exp Mol Med. 2024 Aug;56(8):1685-1690. Review.
  5. Ali Moussa HY, Shin KC, Ponraj J, Park SH, Lee OS, Mansour S, Park Y#. PIP2 Is an electrostatic Catalyst for Vesicle Fusion by Lowering the Hydration Energy: Arresting Vesicle Fusion by Masking PIP2. ACS Nano. 2024 May 21;18(20):12737-12748. Highlighted as a Supplementary Cover.
  6. Shin KC, Ali G, Ali Moussa HY, Gupta V, de la Fuente A, Kim HG, Stanton LW, Park Y#. Deletion of TRPC6, an autism risk gene, induces hyperexcitability in cortical neurons derived from human pluripotent stem cells. Mol Neurobiol. 2023 Aug 8.
  7. Ali Moussa HY, Shin KC, Ponraj J, Kim SJ, Ryu JK, Mansour S, Park Y#. Requirement of cholesterol for calcium-dependent vesicle fusion by strengthening synaptotagmin-1-induced membrane bending. Adv Sci. 2023 May;10(15):e2206823. Highlighted as a Frontispiece.
  8. Ali Moussa HY, Park Y#. Electrostatic regulation of the cis- and trans-membrane interactions of synaptotagmin-1. Sci Rep. 2022 Dec 27;12(1):22407.
  9. Ali Moussa HY, Manaph N, Ali G, Maacha S, Shin KC, Ltaief SM, Gupta V, Tong Y, Ponraj J, Salloum-Asfar S, Mansour S, Al-Shaban FA, Kim HG, Stanton LW, Grivel JC, Abdulla SA, Al-Shammari AR#, Park Y#. Single extracellular vesicle analysis using flow cytometry for neurological disorder biomarkers. Front Integr Neurosci. 2022 May 17;16:879832.
  10. Birinci Y, Preobraschenski J, Ganzella M, Jahn R, Park Y#. Isolation of large dense-core vesicles from bovine adrenal medulla for functional studies. Sci Rep. 2020 May 5;10(1):7540.
  11. Park Y# and Ryu JK#. Models of synaptotagmin-1 to trigger Ca2+-dependent vesicle fusion. FEBS Lett. 2018 Nov;592(21):3480-3492.
  12. Park Y#, MicroRNA exocytosis by vesicle fusion in neuroendocrine cells. Front Endocrinol. 2017 Dec 22;8:355.
  13. Gümürdü A, Yildiz R, Eren E, Karakülah G, Ünver T, GENÇ Ş, and Park Y#. MicroRNA exocytosis by large dense-core vesicle fusion. Sci Rep. 2017 Mar 30;7:45661.
  14. Park Y, Seo JB, Fraind A, Pérez-Lara A, Yavuz H, Han K, Jung SR, Kattan I, Walla PJ, Choi MY, Cafiso DS, Koh DS, Jahn R. Synaptotagmin-1 binds to PIP2-containing membrane but not to SNAREs at physiological ionic strength. Nature Struct Mol Biol. 2015 Oct;22(10):815-823.
  15. Park Y, Vennekate W, Yavuz H, Preobraschenski J, Hernandez JM, Riedel D, Walla PJ, Jahn R. α-SNAP interferes with the zippering of the SNARE membrane fusion machinery. J Biol Chem. 2014 Jun 6;289(23):16326-16335.
  16. Park Y, Hernandez J. M, van den Bogaart G, Ahmed S, Holt M, Riedel D, and Jahn R. Controlling synaptotagmin activity by electrostatic screening. Nature Struct Mol Biol. 2012 Oct;19(10):991-997.
  17. Park Y and Kim KT. Dominant role of lipid rafts L-type calcium channel in activity-dependent potentiation of large dense-core vesicle exocytosis. J Neurochem. 2009 Jul;110(2):520-529.
  18. Park Y and Kim KT. Short-term plasticity of small synaptic vesicle (SSV) and large dense-core vesicle (LDCV) exocytosis. Cell Signal. 2009 Oct;21(10):1465-70.
  19. Park YS, Choi YH, Park CH, Kim KT. Non-genomic glucocorticoid effects on activity-dependent potentiation of catecholamine release in chromaffin cells. Endocrinology. 2008 Oct;149(10):4921-7.
  20. Park YS, Hur EM, Choi BH, Kwak E, Jun DJ, Park SJ, Kim KT. Involvement of protein kinase C-epsilon in activity-dependent potentiation of large dense-core vesicle exocytosis in chromaffin cells. J Neurosci. 2006 Aug 30;26(35): 8999-9005.
  21. (Cover article) Park YS, Jun DJ, Hur EM, Lee SK, Suh BS, Kim KT. Activity-dependent potentiation of large dense-core vesicle release modulated by mitogen-activated protein kinase(MAPK)/ERK signaling. Endocrinology. 2006 Mar;147(3):1349-56.

Latest News

  • Great news! Our research article was accepted in Science Advances (Feb. 2025).
  • Our method paper was accepted in Methods Mol Biol. (Jan. 2025).
  • Yongsoo presented in the 2nd Health Innovation at HBKU Joint Symposium (17-18 Nov. 2024).
  • Congratulations Houda! Our EV biomarker paper was accepted in Front. Mol. Biosci. (Nov. 2024).
  • Congratulations Shin! Our review article about cholesterol in neurological disorders was accepted in Exp Mol Med. (Aug. 2024).
  • Dr. Yongsoo Park was invited as a seminar speaker in the Interdisciplinary Program in Brain Science, Seoul National University (30 May. 2024).
  • Our paper was accepted in ACS Nano and highlighted as a Supplementary Cover (May 2024).
  • We are awarded the Academic Research Grant (ARG), Cycle 1 (Nov. 2023).
  • Yongsoo presented in the CHLS research seminar, Qatar (18 Oct. 2023).
  • Yongsoo gave a presentation in a virt

Latest News

Contact



    Address

    Qatar Biomedical Research Institute (QBRI),
    College of Health & Life Sciences (CHLS),
    Hamad Bin Khalifa University (HBKU),
    Education City, Doha, Qatar

    PHONE & E-MAIL

    Email: ypark@hbku.edu.qa