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Nagendran Ramalingam, Ph.D.

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Available: 01/15/23, Expires: 03/31/23

In Parkinson’s disease and other synucleinopathies, the elevation of a-synuclein phosphorylated at Serine129 (pS129) is a widely cited marker of pathology. However, the physiological role of pS129 has remained undefined. Recently, using multiple approaches, we showed for the first time that pS129 functions as a physiological regulator of neurotransmission (in press, NPJ Parkinson's disease). This work has opened up several important avenues to understanding the pathophysiology of a-synuclein. One of them is to learn whether we can distinguish physiological pS129 from its pathological counterpart at the molecular level, which can help us design better pS129-based biomarkers and therapeutic approaches. This project requires multidisciplinary approaches (e.g., cell biology, biochemistry, mouse behavior, biophysics, imaging, and electrophysiology to address this question. Therefore, the project can be tailored depending on the student's interests and prior expertise.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. RF1AG079569 (Jasmeer Chatwal) Aug 12, 2022 - Jul 31, 2027
    Leveraging Heterogeneity in Autosomal Dominant AD to Elucidate Pathophysiology and Improve AD Biomarkers
    Role: Co-Investigator
  2. RF1NS122880 (Ulf Dettmer) Jul 1, 2022 - Jun 30, 2027
    Polo-like-kinase-2-dependent a-synuclein serine-129 phosphorylation: a physiological role during synaptic activity
    Role Description: The goal of this project is to understand the physiological role of a-synuclein serine-129 phosphorylation at active synapses during neuronal activity.
    Role: Co-Investigator
  3. PIN award (Nagendran Ramalingam) Jan 1, 2019 - Jan 31, 2022
    Program in Neuroscience, Brigham & Women's Hospital
    The role of alpha-synuclein tetramerization at the synapse
    Role Description: The goal of this project was to characterize the structure-function relationship of a-synuclein during neuronal activity.
    Role: Principal Inverstigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Ramalingam N, Jin SX, Moors TE, Fonseca-Ornelas L, Shimanaka K, Lei S, Cam HP, Watson AH, Brontesi L, Ding L, Hacibaloglu DY, Jiang H, Choi SJ, Kanter E, Liu L, Bartels T, Nuber S, Sulzer D, Mosharov EV, Chen WV, Li S, Selkoe DJ, Dettmer U. Dynamic physiological a-synuclein S129 phosphorylation is driven by neuronal activity. NPJ Parkinsons Dis. 2023 Jan 16; 9(1):4. PMID: 36646701; PMCID: PMC9842642.
  2. Brontesi L, Imberdis T, Ramalingam N, Dettmer U. The effects of KTKEGV repeat motif and intervening ATVA sequence on a-synuclein solubility and assembly. J Neurochem. 2023 Jan 10. PMID: 36625497.
    Citations:    Fields:    
  3. Tripathi A, Alnakhala H, Terry-Kantor E, Newman A, Liu L, Imberdis T, Fanning S, Nuber S, Ramalingam N, Selkoe D, Dettmer U. Pathogenic Mechanisms of Cytosolic and Membrane-Enriched a-Synuclein Converge on Fatty Acid Homeostasis. J Neurosci. 2022 03 09; 42(10):2116-2130. PMID: 35086904; PMCID: PMC8916762.
    Citations:    Fields:    Translation:AnimalsCells
  4. Kim TE, Newman AJ, Imberdis T, Brontesi L, Tripathi A, Ramalingam N, Fanning S, Selkoe D, Dettmer U. Excess membrane binding of monomeric alpha-, beta- and gamma-synuclein is invariably associated with inclusion formation and toxicity. Hum Mol Genet. 2021 11 16; 30(23):2332-2346. PMID: 34254125; PMCID: PMC8600006.
    Citations:    Fields:    Translation:HumansCells
  5. Ramalingam N, Dettmer U. Temperature is a key determinant of alpha- and beta-synuclein membrane interactions in neurons. J Biol Chem. 2021 Jan-Jun; 296:100271. PMID: 33428933.
    Citations: 4     Fields:    Translation:HumansAnimalsCells
  6. Ho GPH, Ramalingam N, Imberdis T, Wilkie EC, Dettmer U, Selkoe DJ. Upregulation of Cellular Palmitoylation Mitigates a-Synuclein Accumulation and Neurotoxicity. Mov Disord. 2021 02; 36(2):348-359. PMID: 33103814; PMCID: PMC8887921.
    Citations: 8     Fields:    Translation:HumansAnimalsCells
  7. Terry-Kantor E, Tripathi A, Imberdis T, LaVoie ZM, Ho GPH, Selkoe D, Fanning S, Ramalingam N, Dettmer U. Rapid Alpha-Synuclein Toxicity in a Neural Cell Model and Its Rescue by a Stearoyl-CoA Desaturase Inhibitor. Int J Mol Sci. 2020 Jul 22; 21(15). PMID: 32707907.
    Citations: 6     Fields:    Translation:HumansCells
  8. Imberdis T, Negri J, Ramalingam N, Terry-Kantor E, Ho GPH, Fanning S, Stirtz G, Kim TE, Levy OA, Young-Pearse TL, Selkoe D, Dettmer U. Cell models of lipid-rich a-synuclein aggregation validate known modifiers of a-synuclein biology and identify stearoyl-CoA desaturase. Proc Natl Acad Sci U S A. 2019 10 08; 116(41):20760-20769. PMID: 31548371.
    Citations: 27     Fields:    Translation:HumansAnimalsCells
  9. Litschko C, Brühmann S, Csiszár A, Stephan T, Dimchev V, Damiano-Guercio J, Junemann A, Körber S, Winterhoff M, Nordholz B, Ramalingam N, Peckham M, Rottner K, Merkel R, Faix J. Functional integrity of the contractile actin cortex is safeguarded by multiple Diaphanous-related formins. Proc Natl Acad Sci U S A. 2019 02 26; 116(9):3594-3603. PMID: 30808751; PMCID: PMC6397521.
    Citations: 16     Fields:    Translation:HumansAnimalsCells
  10. Imberdis T, Fanning S, Newman A, Ramalingam N, Dettmer U. Studying a-Synuclein Conformation by Intact-Cell Cross-Linking. Methods Mol Biol. 2019; 1948:77-91. PMID: 30771172.
    Citations: 6     Fields:    Translation:Cells
  11. Fanning S, Haque A, Imberdis T, Baru V, Barrasa MI, Nuber S, Termine D, Ramalingam N, Ho GPH, Noble T, Sandoe J, Lou Y, Landgraf D, Freyzon Y, Newby G, Soldner F, Terry-Kantor E, Kim TE, Hofbauer HF, Becuwe M, Jaenisch R, Pincus D, Clish CB, Walther TC, Farese RV, Srinivasan S, Welte MA, Kohlwein SD, Dettmer U, Lindquist S, Selkoe D. Lipidomic Analysis of a-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment. Mol Cell. 2019 03 07; 73(5):1001-1014.e8. PMID: 30527540; PMCID: PMC6408259.
    Citations: 81     Fields:    Translation:HumansAnimalsCells
  12. Sun X, Aimé P, Dai D, Ramalingam N, Crary JF, Burke RE, Greene LA, Levy OA. Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease. Exp Neurol. 2018 05; 303:95-107. PMID: 29432724; PMCID: PMC5864566.
    Citations: 15     Fields:    Translation:HumansAnimalsCells
  13. Dettmer U, Ramalingam N, von Saucken VE, Kim TE, Newman AJ, Terry-Kantor E, Nuber S, Ericsson M, Fanning S, Bartels T, Lindquist S, Levy OA, Selkoe D. Loss of native a-synuclein multimerization by strategically mutating its amphipathic helix causes abnormal vesicle interactions in neuronal cells. Hum Mol Genet. 2017 09 15; 26(18):3466-3481. PMID: 28911198; PMCID: PMC5884392.
    Citations: 42     Fields:    Translation:HumansAnimalsCells
  14. Bartolini F, Andres-Delgado L, Qu X, Nik S, Ramalingam N, Kremer L, Alonso MA, Gundersen GG. An mDia1-INF2 formin activation cascade facilitated by IQGAP1 regulates stable microtubules in migrating cells. Mol Biol Cell. 2016 06 01; 27(11):1797-808. PMID: 27030671; PMCID: PMC4884070.
    Citations: 24     Fields:    Translation:AnimalsCells
  15. Ramalingam N, Franke C, Jaschinski E, Winterhoff M, Lu Y, Brühmann S, Junemann A, Meier H, Noegel AA, Weber I, Zhao H, Merkel R, Schleicher M, Faix J. A resilient formin-derived cortical actin meshwork in the rear drives actomyosin-based motility in 2D confinement. Nat Commun. 2015 Sep 29; 6:8496. PMID: 26415699.
    Citations: 21     Fields:    Translation:AnimalsCells
  16. Morris EJ, Nader GP, Ramalingam N, Bartolini F, Gundersen GG. Kif4 interacts with EB1 and stabilizes microtubules downstream of Rho-mDia in migrating fibroblasts. PLoS One. 2014; 9(3):e91568. PMID: 24658398; PMCID: PMC3962350.
    Citations: 22     Fields:    Translation:AnimalsCells
  17. Bartolini F, Ramalingam N, Gundersen GG. Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1. Mol Biol Cell. 2012 Oct; 23(20):4032-40. PMID: 22918941.
    Citations: 40     Fields:    Translation:AnimalsCells
  18. Ramalingam N, Zhao H, Breitsprecher D, Lappalainen P, Faix J, Schleicher M. Phospholipids regulate localization and activity of mDia1 formin. Eur J Cell Biol. 2010 Oct; 89(10):723-32. PMID: 20619927.
    Citations: 43     Fields:    Translation:AnimalsCells
  19. Joseph JM, Fey P, Ramalingam N, Liu XI, Rohlfs M, Noegel AA, Müller-Taubenberger A, Glöckner G, Schleicher M. The actinome of Dictyostelium discoideum in comparison to actins and actin-related proteins from other organisms. PLoS One. 2008 Jul 09; 3(7):e2654. PMID: 18612387.
    Citations: 19     Fields:    Translation:AnimalsCells
  20. Arasada R, Son H, Ramalingam N, Eichinger L, Schleicher M, Rohlfs M. Characterization of the Ste20-like kinase Krs1 of Dictyostelium discoideum. Eur J Cell Biol. 2006 Sep; 85(9-10):1059-68. PMID: 16842885.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  21. Ranga U, Shankarappa R, Siddappa NB, Ramakrishna L, Nagendran R, Mahalingam M, Mahadevan A, Jayasuryan N, Satishchandra P, Shankar SK, Prasad VR. Tat protein of human immunodeficiency virus type 1 subtype C strains is a defective chemokine. J Virol. 2004 Mar; 78(5):2586-90. PMID: 14963162; PMCID: PMC369202.
    Citations: 92     Fields:    Translation:HumansCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.