Research

Translational Biology of Neurodegenerative Diseases

Our laboratory, through the integration of multidisciplinary approaches employing protein engineering, biochemical, biophysical, and cell biology methods, is interested in studying the molecular mechanisms that contribute to the development of neurodegenerative diseases such as motor neuron diseases and Parkinson’s disease. Proteins, the most abundant macromolecules in cells, in their native conformations, play diverse roles in cellular functions. In neurodegenerative diseases, specific proteins are found as abnormal oligomeric and filamentous assemblies in the cells of the nervous system and are believed to contribute to the pathogenesis of respective diseases. The major contributors to these diseases are primarily in the quest. However, factors such as aging and inherited mutations of specific proteins play a role in forming abnormal assemblies and concomitant disease mechanisms across scales of proteins, cells, and brain regions.

Interestingly, many of these neurodegenerative diseases share commonalities and heterogeneities, ranging from the levels of cellular proteins to clinical symptoms. However, the molecular basis of this phenomenon remains to be explored. Along with our efforts in studying disease mechanisms, our lab aims to translate laboratory findings into methodologies and tools to assist the academic community. We also focus on developing close-to-human disease models based on cellular systems, ultimately used to discover effective therapeutic options.

Publications and Patents

Selected Publications

1. Kumar, S. T., Nazarov, S., Porta, S., Maharjan, N., Cendrowska, U., Kabani, M., Finamore, F., Xu, Y., Lee, V. M., & Lashuel, H. A. (2023). Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage. Nature Neuroscience, 26(6), 983–996. https://doi.org/10.1038/s41593-023-01341-4
2. Kumar, S. T., Mahul-Mellier, A., Hegde, R. N., Rivière, G., Moons, R., De Opakua, A. I., Magalhães, P., Rostami, I., Donzelli, S., Sobott, F., Zweckstetter, M., & Lashuel, H. A. (2022). A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity. Science Advances, 8(17). https://doi.org/10.1126/sciadv.abn0044
3. Kumar, S. T., Jagannath, S., Francois, C., Vanderstichele, H., Stoops, E., & Lashuel, H. A. (2020). How specific are the conformation-specific α-synuclein antibodies? Characterization and validation of 16 α-synuclein conformation-specific antibodies using well-characterized preparations of α-synuclein monomers, fibrils and oligomers with distinct structures and morphology. Neurobiology of Disease, 146, 105086. https://doi.org/10.1016/j.nbd.2020.105086
4. Kumar, S. T., Donzelli, S., Chiki, A., Syed, M. M. K., & Lashuel, H. A. (2020). A simple, versatile and robust centrifugation‐based filtration protocol for the isolation and quantification of α‐synuclein monomers, oligomers and fibrils: Towards improving experimental reproducibility in α‐synuclein research. Journal of Neurochemistry, 153(1), 103–119. https://doi.org/10.1111/jnc.14955
5. Kumar, S. T., Meinhardt, J., Fuchs, A., Aumüller, T., Leppert, J., Büchele, B., Knüpfer, U., Ramachandran, R., Yadav, J. K., Prell, E., Morgado, I., Ohlenschläger, O., Horn, U., Simmet, T., Görlach, M., & Fändrich, M. (2014). Structure and Biomedical Applications of Amyloid Oligomer Nanoparticles. ACS Nano, 8(11), 11042–11052. https://doi.org/10.1021/nn503960h
6. Kumar, S. T., Leppert, J., Bellstedt, P., Wiedemann, C., Fändrich, M., & Görlach, M. (2015). Solvent Removal Induces a Reversible β-to-α Switch in Oligomeric Aβ Peptide. Journal of Molecular Biology, 428(2), 268–273. https://doi.org/10.1016/j.jmb.2015.05.002
7. Indu, S., Kumar, S. T., Thakurela, S., Gupta, M., Bhaskara, R. M., Ramakrishnan, C., & Varadarajan, R. (2009). Disulfide conformation and design at helix N‐termini. Proteins Structure Function and Bioinformatics, 78(5), 1228–1242. https://doi.org/10.1002/prot.22641
8. Altay, M. F., Kumar, S. T., Burtscher, J., Jagannath, S., Strand, C., Miki, Y., Parkkinen, L., Holton, J. L., & Lashuel, H. A. (2023). Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases. Npj Parkinson S Disease, 9(1). https://doi.org/10.1038/s41531-023-00604-y
9. Kavungal, D., Magalhães, P., Kumar, S. T., Kolla, R., Lashuel, H. A., & Altug, H. (2023). Artificial intelligence–coupled plasmonic infrared sensor for detection of structural protein biomarkers in neurodegenerative diseases. Science Advances, 9(28). https://doi.org/10.1126/sciadv.adg9644
10. Cendrowska, U., Silva, P. J., Ait-Bouziad, N., Müller, M., Guven, Z. P., Vieweg, S., Chiki, A., Radamaker, L., Kumar, S. T., Fändrich, M., Tavanti, F., Menziani, M. C., Alexander-Katz, A., Stellacci, F., & Lashuel, H. A. (2020). Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM. Proceedings of the National Academy of Sciences, 117(12), 6866–6874. https://doi.org/10.1073/pnas.1916176117

Complete publication list: https://scholar.google.com/citations?user=8gGsQzAAAAAJ&hl=en

Fellowships/Awards/Honors

Sep 2024 -   DBT-Ramalingaswami Re-entry Fellowship, India.

Nov 2015 -  High Honors (Magna cum Laude) for PhD thesis, Ulm University, Germany.

May 2014 - German Academic Exchange Service (DAAD) grant, German Federal Ministry of Education and Research (BMBF), Germany.

Sep 2009 -  Dec 2012: Max Planck PhD fellowship, Germany.

July 2007 -  Aug 2009: Junior Research Fellowship, Indian Institute of Science, India.

Current/Past Lab members:

Our laboratory is actively seeking qualified candidates for Ph.D. positions to work on exciting projects in neurodegenerative diseases. For PhD positions, please go through the joining process at NCCS as detailed here: https://www.nccs.res.in/Career/1

We also seek motivated candidates for postdoctoral positions. Write me to learn more about the opportunities.