Magdalena Czeredys_Huntington's disease Group

Huntingtons disease Group logo

Group Leader

dr hab. n. med. Magdalena Czeredys - tel. 22 60 86 540, This email address is being protected from spambots. You need JavaScript enabled to view it. ; room 602

PhD students 

MSc Victoria Graffe Pereira - tel. 22 60 85 41, This email address is being protected from spambots. You need JavaScript enabled to view it. ; room 601

MSc Mahadi Hassan Fahim - tel. 22 60 85 41, This email address is being protected from spambots. You need JavaScript enabled to view it. ; room 601

zdjęcie 1

Research focus

The conducted research aims to understand the molecular mechanisms underlying Huntington’s disease and to develop potential therapeutic strategies using human induced pluripotent stem cell (hiPSC) models.

The main research topics of our group include:

  • Understanding the neurodegenerative and neurodevelopmental basis of Huntington’s disease
  • Obtaining Huntington’s disease models derived from hiPSC
  • Modeling of Huntington’s disease using hiPSC-derived NPCs and MSNs (2D models), organoids and assembloids (3D models)
  • Identification of therapeutic targets in Huntington’s disease using the above-mentioned models
  • Modeling of Huntington’s disease using directly reprogrammed neurons (induced neurons, iN)
  • Understanding Huntington’s disease mechanisms using multi-omics analyses
  • Testing of therapeutic methods based on drugs and genome editing using in vitro models of Huntington’s disease (NPC, neurons, organoids)

Grants

Current projects:

  • “Human iPSC-derived cortico-striatal assembloids as a new model to study neurodevelopmental pathologies induced by mutant Huntingtin” NCN OPUS, no. 2023/49/B/NZ3/04131, 2024 – 2028; Principal Investigator: dr hab. Magdalena Czeredys
  • Innovative platform of organoid modelling and therapy testing in human neurologic and oncologic diseases” grant no. KPOD.07.07-IW.07-0105/24, 2024 – 2025;  
    Principal Investigator: Dr hab. Dawid Walerych, Scientific collaboration /consultant: dr hab.     Magdalena Czeredys
  • “Deciphering the role of Nrf2 in the pathophysiology of phosphomannomutase 2 deficiency” GACR no. 22-18235S, 2022 – 2025; Principal Investigator: Prof. Hana Hansikova and Dr. Nina Ondruskova, Scientific collaboration/investigator: dr hab. Magdalena Czeredys
  • “Molecular genetic causes and biochemical consequences of Congenital disorders of glycosylation” AZV CR no. NU22-07-00474, 2022 – 2025; Principal Investigator: Prof. Hana Hansikova, Scientific collaboration/investigator: dr hab. Magdalena Czeredys

Completed projects:

  • “Linking abnormal Ca2+ signaling and the unfolded protein response with Huntington’s disease pathology in both YAC128 mouse model and iPSC-derived neurons from HD patients” OPUS NCN no. 2019/33/B/NZ3/02889; 2020 – 2024; Principal Investigator: dr hab. Magdalena Czeredys
  • “Role of CacyBP/SIP in the dysregulation of β-catenin ubiquitination in the YAC128 mouse model of Huntington’s disease” NCN SONATA no. 2014/15/D/NZ3/05181; SONATA 8, 2015-2019; Principal Investigator: dr hab. Magdalena Czeredys
  • “Huntingtin-associated Protein 1 Induces Store-Operated Calcium Entry by Activating IP3 Receptor Channels in Huntington’s Disease” FNP BRIDGE, no. POMOST/2013-8/4/0193 2014 – 2015; Principal Investigator: dr hab. Magdalena Czeredys
  • “Pathways of Store-Operated Calcium Entry (SOCE) as a novel therapeutic target in neurodegenerative diseases”. Polish-German-Russian grant ERA.Net RUS funded by EU, NCBR no. NCBR/ERA.Net RUS/03/2012, 2012 – 2014, Investigator: dr hab. Magdalena Czeredys

Collaboration:
Domestic

  • Prof. Dr hab. Marta Olejniczak, Genomic Engineering Department, Institute of Organic Biochemistry Polish Academy of Science
  • Dr. hab. Stanisław Dunin-Horkawicz, Laboratory of Structural Bioinformatics, University of Warsaw Biological and Chemical Research Centre

International

  • Dr. Karolina Pircs and Dr. Attila Szücs, Neurobiology and Neurodegenerative Diseases Group, Institute of Translational Medicine, Semmelweis University
  • Prof. In-Hyun Park, Yale Stem Cell Center
  • Dr. Gabriel Balmus, UK Dementia Research Institute at the University of Cambridge
  • Dr. Hana Hansikova, Laboratory for Study of Mitochondrial Disorders, Department of Pediatric and Adolescent Medicine at Charles University in Prague
  • Prof. Jiri Klempir, Department of Neurology, Centre of Clinical Neuroscience and Institute of Anatomy at Charles University in Prague
  • Prof. Georg Bernhard Landwehrmeyer, Department of Neurology, University of Ulm
  • Dr. Alzbeta Mühlbäck, Department of Neurology, University of Ulm, Isar-Amper-Klinikum, Huntington-Zentrum-Süd, Klinik Taufkirchen
  • Prof. Katsuhiko Mikoshiba, Lab for Cell Calcium Signaling, Shanghai Institute for Immunochemical Studies (SIAIS), ShanghaiTech University


Research methods

  • Advanced cell culture techniques based on hiPSC lines: hiPSC line derivation from fibroblast patients and control individuals, characteristic of hiPSC lines, obtaining of hiPSC-derived NPC cultures, obtaining of hiPSC-derived MSN cultures (striatal neurons), culturing of striatal and cortical organoids derived from hiPSCs, generation of cortico-striatal assembloids, enrichment of organoids with microglia.
  • Obtaining directly reprogrammed neurons (iN)
  • Genome editing of iPSC lines using CRISPR-Cas9
  • Culturing of primary cultures of neurons and astrocytes from mice and rats
  • Derivation and culture of dental pulp stem cells (DPSCs)
  • Lentiviral production
  • Molecular biology and biochemistry methods
  • Single cell calcium imaging
  • Drug screening
  • Microscopic techniques: live imaging, immunocytochemistry; flow cytometry, RNA sequencing
  • Animal models: YAC128 mice (a transgenic mice model of Huntington’s disease)

 

scheme ang 2

 

Equipment

  • ESCO Class II BSC laminar flow cabinet
  • Cell culture incubators (CO2 MCO-171AICUVD, Heal Force Smart Cell)
  • Organoids shaker from Thermo Scientific
  • Water bath
  • ZEISS Axiovert 5 fluorescence microscope with an Axiocam microscope camera
  • LUNA II automatic cell counter
  • Eppendorf Mastercyceler
  • ANTECH Dewar for storing cell lines in liquid nitrogen
  • Centrifuges (Jouan CR3, M-Universal MPW, Eppendorf)

Selected publications

* corresponding author

  • Piechota M, Latoszek E, Liszewska E, Hansíková H, Klempíř J, Mühlbäck A, Landwehrmeyer GB, Kuźnicki J, Czeredys M*. Generation of two human iPSC lines from dermal fibroblasts of adult- and juvenile-onset Huntington's disease patients and two healthy donors. Stem Cell Res. 2023 Sep;71:103194. doi: 10.1016/j.scr.2023.103194.
  • Latoszek E, Piechota M, Liszewska E, Hansíková H, Klempíř J, Mühlbäck A, Landwehrmeyer GB, Kuznicki J, Czeredys M*. Generation of three human iPSC lines from patients with Huntington's disease with different CAG lengths and human control iPSC line from a healthy donor. Stem Cell Res. 2022 Oct;64:102931. doi: 10.1016/j.scr.2022.102931.
  • Markowska-Barkic A, Lewicka E, Czeredys M, Mitura M, Jagura-Burdzy G*. Deciphering the Regulatory Circuits of RA3 Replication Module - Mechanisms of the Copy Number Control. Int J Mol Sci. 2022 Sep 1;23(17):9964. doi: 10.3390/ijms23179964.
  • Latoszek E, Wiweger M, Ludwiczak J, Dunin-Horkawicz S, Kuznicki J*, Czeredys M*. Siah-1-interacting protein regulates mutated huntingtin protein aggregation in Huntington's disease models. Cell Biosci. 2022 Mar 19;12(1):34. doi: 10.1186/s13578-022-00755-0.
  • Latoszek E, Czeredys M*. Molecular Components of Store-Operated Calcium Channels in the Regulation of Neural Stem Cell Physiology, Neurogenesis, and the Pathology of Huntington's Disease. Front Cell Dev Biol. 2021 Apr 1;9:657337. doi: 10.3389/fcell.2021.657337.
  • Czeredys M*. Dysregulation of Neuronal Calcium Signaling via Store-Operated Channels in Huntington's Disease. Front Cell Dev Biol. 2020 Dec 23;8:611735. doi: 10.3389/fcell.2020.611735.
  • Grzeczkowicz A, Gruszczynska-Biegala J, Czeredys M, Kwiatkowska A, Strawski M, Szklarczyk M, Koźbiał M, Kuźnicki J, Granicka LH*. Polyelectrolyte membrane scaffold sustains growth of neuronal cells. J Biomed Mater Res A. 2019 Apr;107(4):839-850. doi: 10.1002/jbm.a.36599.
  • Czeredys M*, Vigont VA, Boeva VA, Mikoshiba K, Kaznacheyeva EV, Kuznicki J. Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington's Disease. Front Cell Neurosci. 2018 Oct 26;12:381. doi: 10.3389/fncel.2018.00381.
  • Czeredys M*, Maciag F, Methner A, Kuznicki J. Tetrahydrocarbazoles decrease elevated SOCE in medium spiny neurons from transgenic YAC128 mice, a model of Huntington's disease. Biochem Biophys Res Commun. 2017 Feb 19;483(4):1194-1205. doi: 10.1016/j.bbrc.2016.08.106.
  • Czeredys M, Gruszczynska-Biegala J, Schacht T, Methner A, Kuznicki J*. Expression of genes encoding the calcium signalosome in cellular and transgenic models of Huntington's disease. Front Mol Neurosci. 2013 Nov 25;6:42. doi: 10.3389/fnmol.2013.00042.
  • Czeredys M, Samluk Ł, Michalec K, Tułodziecka K, Skowronek K, Nałęcz KA*. Caveolin-1--a novel interacting partner of organic cation/carnitine transporter (Octn2): effect of protein kinase C on this interaction in rat astrocytes. PLoS One. 2013 Dec 13;8(12):e82105. doi: 10.1371/journal.pone.0082105. PMID: 24349196; PMCID: PMC3862573.
  • Tułodziecka K, Czeredys M, Nałęcz KA*. Palmitoylcarnitine affects localization of growth associated protein GAP-43 in plasma membrane subdomains and its interaction with Gα(o) in neuroblastoma NB-2a cells. Neurochem Res. 2013 Mar;38(3):519-29. doi: 10.1007/s11064-012-0944-5. Epub 2012 Dec 9. Erratum in: Neurochem Res. 2013 Nov;38(11):2450-1.
  • Samluk L, Czeredys M, Skowronek K, Nałęcz KA*. Protein kinase C regulates amino acid transporter ATB(0,+). Biochem Biophys Res Commun. 2012 May 25;422(1):64-9. doi: 10.1016/j.bbrc.2012.04.106.
  • Samluk Ł, Czeredys M, Nałęcz KA*. Regulation of amino acid/carnitine transporter B 0,+ (ATB 0,+) in astrocytes by protein kinase C: independent effects on raft and non-raft transporter subpopulations. J Neurochem. 2010 Dec;115(6):1386-97. doi: 10.1111/j.1471-4159.2010.07040.x.
  • Czeredys M, Mysiorek C, Kulikova N, Samluk Ł, Berezowski V, Cecchelli R, Nałecz KA*. A polarized localization of amino acid/carnitine transporter B(0,+) (ATB(0,+)) in the blood-brain barrier. Biochem Biophys Res Commun. 2008 Nov 14;376(2):267-70. doi: 10.1016/j.bbrc.2008.08.122.
  • Kulinska A, Czeredys M, Hayes F, Jagura-Burdzy G*. Genomic and functional characterization of the modular broad-host-range RA3 plasmid, the archetype of the IncU group. Appl Environ Microbiol. 2008 Jul;74(13):4119-32. doi: 10.1128/AEM.00229-08.
  • Miecz D, Januszewicz E, Czeredys M, Hinton BT, Berezowski V, Cecchelli R, Nałecz KA*. Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood-brain barrier. J Neurochem. 2008 Jan;104(1):113-23. doi: 10.1111/j.1471-4159.2007.05024.x.
  • Nałecz KA*, Szczepankowska D, Czeredys M, Kulikova N, Grześkiewicz S. Palmitoylcarnitine regulates estrification of lipids and promotes palmitoylation of GAP-43. FEBS Lett. 2007 Aug 21;581(21):3950-4. doi: 10.1016/j.febslet.2007.07.027.