Senthil Kumar Thangaraj

Scientist-D, BRIC-NCCS

Profile

Senthil Thangaraj received his M.Sc. in Medical Biochemistry from the University of Madras. Later, he moved to Germany for his PhD at the Max Planck Research Unit for Enzymology of Protein Folding and Ulm University. His PhD work elucidated the structural properties and biotechnological applications of protein aggregates commonly associated with neurodegenerative diseases (NDs). Subsequently, he joined postdoctoral positions at the University of Twente in the Netherlands and EPFL in Switzerland. His postdoctoral work provided molecular insights into the regulation of seeding and the pathological properties of TDP-43 aggregates associated with Amyotrophic Lateral Sclerosis (ALS). He also developed novel methods, in vitro assays, and improved preclinical cellular models for advancing drug discovery efforts for NDs. Now that he has returned to India and joined NCCS, he is establishing a research program to elucidate the molecular and cellular mechanisms of abnormal protein aggregation and their roles in NDs such as ALS and Parkinson’s disease. He is also the recipient of a DBT-Ramalingaswami re-entry fellowship.

Current Focus Areas

  • Investigation of common protein assembly mechanisms and their cellular role in the etiology and progression of ALS

  • Elucidation of molecular and biological properties of diverse morphologies of TDP-43 assemblies in related NDs.

  • Examination of the molecular basis of lysosomal dysfunctions association in NDs.

  • Development of personalized cellular models and Biomarker discovery for NDs.

Selected Publications

  • 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.

  • 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).

  • 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.

  • 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.

  • 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.

Skills & Proficiency

Neurodegenerative diseases Protein Biology Protein Engineering Cellular disease models Structural biology Biomarker discovery Drug discovery Parkinson's disease Amyotrophic lateral sclerosis Protein biotechnology
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