Scientist Profile

Senthil Kumar Thangaraj, Ph.D.

Email

senthiltk@nccs.res.in

Research Areas

Pathogenesis and Cellular Response, Macromolecular Structure and Function, Neuroscience

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.

Education

Dr.rer.nat., Max Planck Research Unit for Enzymology of Protein Folding and Ulm University, Ulm, Germany, 2015.

 

Experience

Scientist-D, National Centre for Cell Science, Pune, Maharashtra

Oct 2024-Present

Visiting Professor, EPFL, Lausanne, Switzerland

July 2024

NIH Research Scientist, Center for Brain & Disease Research, VIB-KU Leuven, Leuven, Belgium

2023-2024

Senior Postdoctoral Scientist, Brain Mind Institute, EPFL, Lausanne, Switzerland

2017-2022

Postdoctoral Scientist, University of Twente, the Netherlands

2014-2016

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

 

 

 

Preprints (under Peer Review)

1

Pradhan B, Kumar ST, Wagner J, Gallardo R, Orlando G, De Vleeschouwer M, Madine J, Louros N, Neher JJ, Rousseau F, Schymkowitz J. Medin drives Aβ40 to adopt Aβ42-like fibril polymorphs in vitro. https://doi.org/10.1101/2025.07.17.665283

2

Shafiei N, Mohammed I, Kumar ST, Mahul-Mellier AL, Ekundayo B, Stähli D, Lewis AJ, Stahlberg H. Cryo-EM structure of α-Synuclein Fibrils Harboring the Dementia with Lewy Bodies–Associated E83Q Mutation. https://doi.org/10.64898/2025.12.23.696295

3

Donzeli S, OSullivan SA*, Mahul-Mellier AL*, Ulusoy A, Fusco G, Kumar ST, Syed MMK, Chiki A, Burtscher J, Boussouf MLD, Rostami I, Simone AD, Di Monte DA, Lashuel HA. Post-fibrillization nitration of alpha-synuclein abolishes its seeding activity and pathology formation in primary neurons and in vivo. https://doi.org/10.1101/2023.03.24.534149

 

All Publications (in reverse chronological order)

 

1

Kavungal D, Morro E, Kumar ST, Dagli B, Lashuel HA, Altug H. (2025) Nanoplasmonic Infrared Microarray Sensor Enabling Structural Protein Biomarker-Based Drug Screening for Neurodegenerative Diseases. Adv Sci (Weinh). 2025 Oct;12(39):e00320. https://doi.org/10.1002/advs.202500320.

2

Altay, M. F., Kumar, S. T., Burtscher, J., Jagannath, S., Strand, C., Miki, Y., Parkkinen, L., Holton, J. L., & Lashuel, H. A. (2024). 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

3

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

4

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

5

Kumar ST#, Mahul-Mellier AL#, Hegde RN, Rivière G, Moons R, Ibáñez de Opakua A, Magalhães P, Rostami I, Donzelli S, Sobott F, Zweckstetter M, Lashuel HA. A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity. Sci Adv. 2022 Apr 29;8(17):eabn0044. https://doi.org/10.1126/sciadv.abn0044

6

Kumar ST#, Jagannath S#, Francois C, Vanderstichele H, Stoops E and Lashuel HA*. 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: How specific are the conformation-specific α-synuclein antibodies?. Neurobiol Dis. 2020 Dec; 146:105086. https://doi.org/10.1016/j.nbd.2020.105086

7

Cendrowska U#, Silva PJ#, Ait-Bouziad N, Müller M, Guven ZP, Vieweg S, Chiki A, Radamaker L, Kumar ST, Fändrich M, Tavanti F, Menziani MC, Alexander-Katz A, Stellacci F, Lashuel HA*. Unraveling the Complexity of Amyloid Polymorphism Using Gold Nanoparticles and Cryo-EM. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6866-6874. https://doi.org/10.1073/pnas.1916176117

8

Kumar ST, Donzelli S, Chiki A, Syed MMK and Lashuel HA*. 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. J Neurochem. 2020 Jan 11. https://doi.org/10.1111/jnc.14955

9

Burtscher J, Copin JC, Rodrigues J, Kumar ST, Chiki A, Guillot de Suduiraut I, Sandi C and Lashuel HA*. Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology. Neurobiol Aging. 2019 Nov;83:11-20. https://doi.org/10.1016/j.neurobiolaging.2019.08.007

10

Garvey M#, Baumann M#, Wulff M, Kumar ST, Markx D, Morgado I, Knüpfer U, Horn U, Mawrin C, Balbach J and Fändrich M*. Molecular architecture of Aβ fibrils grown in cerebrospinal fluid solution and in a cell culture model of Aβ plaque formation. Amyloid. 2016, Jun; 23(2):76-85. 10.3109/13506129.2016.1146989

11

Kumar ST, Leppert J, Bellstedt P, Fändrich M* and Görlach M*. Solvent removal induces a reversible β to α switch in oligomeric Aβ peptide. J Mol Biol. 2016, Jan 29; 428(2 Pt A):268-73. https://doi.org/10.1016/j.jmb.2015.05.002

12

Gopalswamy M#, Kumar A#, Adler J, Baumann M, Henze M, Kumar ST, Scheidt HA, Huster D, Fändrich M*, Balbach J*. Structural characterization of amyloid fibrils from the human parathyroid hormone. Biochim Biophys Acta. 2015, Apr; 1854(4):249-57. doi: 10.1016/j.bbapap.2014.12.020

13

Kumar ST, Meinhardt J, Fuchs A-K, Aumuller T, Leppert J, Büchele B, Knüpfer U, Ramachandran R, Yadav JK, Prell E, Morgado I, Ohlenschläger O, Horn U, Simmet T, Görlach M, Fändrich M*. Structure and applicative potential of amyloid oligomer nanoparticles. ACS Nano. 2014, 8: 11042-52. https://doi.org/10.1021/nn503960h

14

Roan N, Liu H, Usmani S, Neidleman J, Muller J, Gawanbacht A, Zirafi O, Chu S, Dong M, Kumar ST, Smith J, Pollard K, Fändrich M, Kirchhoff F, Münch J, Witkowska E and Greene W*. Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection. J Virol. 2014, 88(13):7221-34. doi: 10.1128/JVI.00269-14

15

Haupt C, Bereza M, Kumar ST, Kieninger B, Morgado I, Hortschansky P, Fritz G, Röcken C, Horn U and Fändrich M*. Pattern recognition with a fibril-specific antibody fragment reveals the surface variability of natural amyloid fibrils. J Mol Biol. 2011, 408: 529-40. doi: 10.1016/j.jmb.2011.02.032

16

Haupt C, Morgado I, Kumar ST, Parthier C, Bereza M, Hortschansky P, Stubbs MT, Horn U and Fändrich M*. Amyloid fibril recognition with the conformational B10 antibody fragment depends on electrostatic interactions. J Mol Biol. 2011, 405: 341-8. doi: 10.1016/j.jmb.2010.10.059.

17

Indu S#, Kumar ST#, Thakurela S, Gupta M, Bhaskara RM, Ramakrishnan C and Varadarajan R*. Disulfide conformation and design at helix N-termini. Proteins. 2010, 78: 1228-42. https://doi.org/10.1002/prot.22641

 

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.

 

Funding/Collaborations

DBT Ramalingaswami Re-entry Fellowship (Research grant)

ANRF Prime Minister Early Career Research Grant

NCCS Intramural funds

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.


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Last updated On : 29 January 2026 04:21

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