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Nagendran Ramalingam, Ph.D.

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Overview

Mentoring
Available: 01/01/00, Expires: 04/30/24

a-Synuclein (aS), a product of SNCA, is an abundant presynaptic protein that regulates neurotransmission. aS orchestrates neurotransmitter release by synaptic vesicle cycling, SNARE assembly, clustering of synaptic vesicles, and dilation of the fusion pore during exocytosis. aS is also a key protein implicated in a broad class of neurodegenerative disorders termed “synucleinopathies”, which encompasses Parkinson’s disease (PD), dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). The pathological aS deposits, Lewy Bodies (LBs), and Lewy Neurites (LNs) are also documented in Alzheimer’s disease and related forms of dementia, thus extending the list of dementias with LB pathology. DLB and PD with dementia (PDD) are collectively termed Lewy Body Dementia (LBD). Remarkably, about 90% of aS in the LB and LN is acknowledged to be present in its serine-129 phosphorylated form (pS129). Therefore, pS129 is widely used as a surrogate marker for pathology. However, we recently demonstrated that physiological pS129, triggered by neuronal activity, positively regulates synaptic transmission. These unexpected and intriguing results raise the critical question of whether normal and abnormal pS129 can be distinguished. Given our expertise in studying normal pS129, we are in the unique position to test whether the properties of normal pS129 are different from abnormal pS129. This medical student project will a) help distinguish normal and abnormal pS129, b) help us better understand the process leading to the pathology, c) further our understanding and refine pS129 as a biomarker for diseases of LBD and related synucleinopathies including PD, and eventually contribute to devising meaningful therapeutic interventions. An ideal full-time student: 1) is expected to design and perform experiments in a collaborative wet lab environment, and 2) will work with mice & rats, cultured rodent neurons, and postmortem human brain lysates.


Research
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. RF1NS133979 (Ulf Dettmer and Nagendran Ramalingam) Aug 1, 2023 - Jul 31, 2028
    NIH
    How serine-129 phosphorylation status affects the spreading of a-synuclein pathology in vivo: a study in knock-in animals.
    Role Description: The goal of this project is to explain the contribution of a-synuclein serine-129 phosphorylation in synucleinopathies mechanistically.
    Role: Principal Investigator
  2. RF1AG079569 (Jasmeer Chatwal) Aug 12, 2022 - Jul 31, 2027
    NIH
    Leveraging Heterogeneity in Autosomal Dominant AD to Elucidate Pathophysiology and Improve AD Biomarkers.
    Role Description: The goal of this project is to stratify AD pathophysiology using plasma and CSF biomarkers.
    Role: Co-Investigator
  3. RF1NS122880 (Ulf Dettmer and Nagendran Ramalingam) Jul 1, 2022 - Jun 30, 2027
    NIH
    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: Principal Investigator
  4. 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

Bibliographic
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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.