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Translational diseases models and neurodegeneration

Laboratory of Experimental Medicine
Junior research group

Our group, Translational Disease Models and Neurodegeneration, investigates the molecular and cellular mechanisms that drive neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and frontotemporal dementias. We study how disease-associated proteins misfold, aggregate, and spread, and how these events contribute to neuronal dysfunction and disease progression.

We aim to identify strategies that can slow or prevent these pathological processes. Our work encompasses peptide- and small–molecule–based approaches, as well as emerging technologies such as targeted protein degradation, with a focus on modulating protein aggregation, neuroinflammatory signaling, and other mechanisms central to neurodegeneration. A major emphasis is placed on linking mechanistic insights to translational applications through the development of biomarker platforms that can detect early molecular changes and support therapeutic evaluation.

We use a diverse set of experimental systems, including iPSC-derived neurons, 3D neural cultures, organoids, microfluidic co-culture platforms, and established rodent models. Together, these complementary approaches enable us to construct a comprehensive understanding of disease mechanisms and contribute to the development of effective diagnostic tools and disease-modifying therapies.

  • Mechanisms of protein aggregation and spreading
    We study how tau and α-synuclein aggregates form, how mutations alter their structure, and how these assemblies propagate through neural systems.
  • Targeted modulation of disease-driving proteins
    We design and evaluate peptide inhibitors and small-molecule modulators targeting disease-defining motifs such as the VQIVYK region of tau and the NAC domain of α-synuclein, alongside BTK-centered strategies including PROTAC approaches.
  • Functional biomarkers for early detection
    We advance seed amplification assays (RT-QuIC and IP/RT-QuIC) to detect and characterize pathological tau and α-synuclein seeds in patient samples, aiming to improve diagnostic precision and therapeutic monitoring.
  • Human-relevant cellular and tissue models
    We employ iPSC-derived neurons, 3D neural cultures, organoids, and microfluidic BBB models to recreate disease mechanisms and evaluate therapeutic interventions in physiologically meaningful settings.
  • Translational pharmacology and drug repurposing
    We explore kinase-driven pathways, including BTK, and assess repurposed anticancer and targeted agents for their relevance to neurodegenerative disease mechanisms.
  • Peptide inhibitors targeting α-synuclein seed activity
    Developing and validating NAC-focused peptide inhibitors in cellular models, patient-derived seed assays, and mouse models of synucleinopathy.
  • Tau mutation–sensitive inhibitor profiling
    Investigating how specific tau mutations alter aggregation behavior and determining which VQIVYK-targeting agents are most effective against mutation-driven forms of tau pathology.
  • Seed-based biomarker platforms
    Applying automated immunoprecipitation and RT-QuIC workflows to analyze α-synuclein and tau seeds from clinical samples, linking seed biology to therapeutic testing.
  • Advanced iPSC and 3D disease models
    Building and applying iPSC-derived neuronal systems, organoids, and engineered 3D co-cultures to test aggregation, spreading, neuroinflammation, and responses to targeted therapeutics.
  • BTK-directed therapeutic development
    Designing and evaluating BTK inhibitors and BTK-oriented PROTAC degraders, and assessing their impact on neuroinflammatory signaling and aggregation-linked pathology.
ALLADI, C., I. KOZLOV, P. SKOUPILOVÁ, L. MALINA, S. ROY, V. DAS
Structural and functional insights into the selective inhibition of mutant tau aggregation by purpurin and oleocanthal in frontotemporal dementia. Protein Science. 2025, 34(9), e70240, ISSN: 0961-8368, PMID: 40862394,  PDF.
DAS, V., L. DIOMEDE, L. MALINA, M. MOSCONI, N. ANNADURAI
Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system. Biophysical Journal. 2025, ISSN: 0006-3495 , PMID: 40515399,
DEVIATOV, A., I. KOZLOV, V. DAS
Differentiation of SH-SY5Y Cells into Cortical Neuron-like Cells for Tauopathy Modeling and Seeding Assays. Molecular Neurobiology. 2025, ISSN: 0893-7648, PMID: 40467940,  PDF.
Projekt: The role of tumor hypoxia in the emergence of acquired resistance to drugs aimed at microtubules
Vedoucí: Das Viswanath M.Sc., Ph.D.
K dispozici: 1
Určeno pro: Doktorské studium
Souhrn: 1 place in full-time study
Projekt: Generation of 3D human neuronal cultures: application to modeling CNS diseases
Vedoucí: Das Viswanath M.Sc., Ph.D.
K dispozici: 1
Určeno pro: Magisterské studium
Souhrn: -
Projekt: Biochemical and cellular analysis of amyloid staining agents in models of tauopathies and synucleopathies
Vedoucí: Das Viswanath M.Sc., Ph.D.
K dispozici: 1
Určeno pro: Magisterské studium
Souhrn: -
Projekt: Investigating Effects of Aggregates of Intrinsically Disordered Proteins on Microglia: Implication for Neurodegenerative Diseases
Vedoucí: Das Viswanath M.Sc., Ph.D.
K dispozici: 1
Určeno pro: Magisterské studium
Souhrn: -
Projekt: Efficacy of Bruton Tyrosine Kinase Inhibitors Against Neuroinflammation in Neurodegenerative Diseases
Vedoucí: Das Viswanath M.Sc., Ph.D.
K dispozici: 1
Určeno pro: Magisterské studium
Souhrn: -
Projekt: Systems approaches to understanding aging and neurodegeneration
Vedoucí: Das Viswanath M.Sc., Ph.D.
K dispozici: 2
Určeno pro: Doktorské studium
Projekt: Role of axonal transport and pathology in neurodegeneration
Vedoucí: Das Viswanath M.Sc., Ph.D.
K dispozici: 2
Určeno pro: Doktorské studium
Projekt: Research and development of agents for cancer, neurodegenerative and infectious diseases
Vedoucí: De Sanctis Juan Bautista Ph.D., Hajdúch Marián M.D., Ph.D., Džubák Petr M.D., Ph.D., Urban Milan Ph.D., Das Viswanath M.Sc., Ph.D.
K dispozici: 5
Určeno pro: Doktorské studium
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