Dr. Sivaprakasam Ramamoorthy
Education and training:
MSc, Annamalai University, India.
PhD, Medical University of Vienna, Austria.
Postdoc, Duke University Medical Center, North Carolina, USA.
Senior postdoc, Icahn School of Medicine, New York, USA.
Protein homeostasis is a complex cellular process that regulates protein synthesis and degradation. This homeostatic process is critical for cellular health and the overall health of the organism. The ubiquitin-proteasome system and the autophagolysosome are the primary degraders of aged or misfolded proteins. Impaired functional protein degradation pathways result in the accumulation of misfolded toxic proteins, which have been linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Protein degradation pathways have been extensively studied using single cell models such as yeast. Neurodegenerative diseases, on the other hand, are associated with higher organisms such as humans, where multiple cell types or organs coexist to influence each other. However, it is unclear how the interaction of different cell types or organs influences one’s proteostasis (cell non-autonomous proteostasis). Efforts to elucidate the systemic regulation of proteostasis will aid in the comprehension of the molecular underpinnings of the normal aging process and neurodegenerative diseases. To this end, our lab seeks to understand 1) how systemic inflammation influences neuronal proteostasis in aging and neurodegenerative diseases; 2) the role of senescent glial cells in neuronal proteostasis; and 3) the molecular basis of tau protein propagation across the brain regions.
- Saroja SR, Gorbachev K, TCW J, Goate AM, Pereira AC. Astrocyte-secreted glypican-4 drives APOE4-depedent tau phosphorylation. PNAS. 2022. https://www.biorxiv.org/content/10.1101/2021.07.07.451493v2.
- Saroja SR, Sharma A, Hof PR, Pereira AC. Differential expression of tau species and the association with cognitive decline and synaptic loss in Alzheimer’s disease. Alzheimer’s & Dementia (2021).
- Kazim SF*, Sharma A*, Saroja SR*, Seo J, Larson CS, Ramakrishnan A, Blitzer RD, Shen L, Peña CJ, Crary JF, Shimoda LA, Nestler EJ, Pereira AC. Chronic intermittent hypoxia enhances pathological tau seeding, propagation, and accumulation, and exacerbates Alzheimer’s-like memory and synaptic plasticity deficits and molecular signatures. Biological Psychiatry (2021), doi:10.1016/j.biopsych.2021.02.973. *co-first authors
- Kalaba, P., Aher, N. Y., Ilic, M., Dragacevic, V., … Saroja SR… et al. (2017). Heterocyclic Analogues of Modafinil as Novel, Atypical Dopamine Transporter Inhibitors. Journal of Medicinal Chemistry, 60(22), 9330–9348.
- Saroja SR, Aher YD, Kalaba P, Aher NY, Zehl M, Korz V, et al (2016). A novel heterocyclic compound targeting the dopamine transporter improves performance in the radial arm maze and modulates dopamine receptors D1-D3. Behav Brain Res 312: 127–137.
- Aher YD, Subramaniyan S, Shanmugasundaram B, Sase A, Saroja SR, Holy M, et al (2016). A Novel Heterocyclic Compound CE-104 Enhances Spatial Working Memory in the Radial Arm Maze in Rats and Modulates the Dopaminergic System. Front Behav Neurosci 10: 20.
- Sase A, Aher YD, Saroja SR, Ganesan MK, Sase S, Holy M, et al (2016). A heterocyclic compound CE-103 inhibits dopamine reuptake and modulates dopamine transporter and dopamine D1-D3 containing receptor complexes. Neuropharmacology 102: 186–196.
- Karabacak Y, Sase S, Aher YD, Sase A, Saroja SR, Cicvaric A, et al (2015). The effect of modafinil on the rat dopamine transporter and dopamine receptors D1-D3 paralleling cognitive enhancement in the radial arm maze. Front Behav Neurosci 9: 215.
- Saroja SR, Kim E-J, Shanmugasundaram B, Höger H, Lubec G (2014). Hippocampal monoamine receptor complex levels linked to spatial memory decline in the aging C57BL/6J. Behav Brain Res 264:1–8.
- Saroja SR, Sase A, Kircher SG, Wan J, Berger J, Höger H, et al (2014). Hippocampal proteoglycans brevican and versican are linked to spatial memory of Sprague-Dawley rats in the morris water maze. J Neurochem 130: 797–804.
We are looking for a Project Assistant or Postdoctoral Fellow to study the molecular basis of tau pathology in Alzheimer’s disease using human postmortem brains along with in vitro and in vivo models.
Qualifications: Applicants for the Project Assistant position should preferably have a master’s degree in Life Sciences. Postdoctoral candidates should have a PhD and a strong publication record.
Centre for Brain Research
Indian Institute of Science Campus
CV Raman Avenue
Bangalore 560012. India.
Telephone: Office +91 80 2293 3748