Author interview: Shivangi Sharma was a Ph.D. graduate student (2023) at Prof. Anirban Basu’s lab, National Brain Research Centre, Haryana, India. She has an expertise in molecular neurobiology, focusing on the regenerative potential of NSPCs in neurodegenerative disorders. She is currently pursuing a Postdoc at University of Manitoba, Canada (2024-Present).
Lab: Prof. Anirban Basu, Ph.D., National Brain Research Centre, Manesar, Haryana, India
Research Summary: This research identifies PARP-16 as a key regulator of unfolded protein response in neural stem/progenitor cells during JEV infection, suggesting that targeting PARP-16 could mitigate NSPC dysfunction and help recover from long-term neurological impairments.
What was the core problem you aimed to solve with this research?
Neural stem/progenitor cells (NSPCs) are pluripotent cells that proliferate and differentiate into neurons and glia in response to CNS injury. In neurotropic viral infections like Japanese Encephalitis Virus (JEV), NSPC dysfunction, impaired neurogenesis, and neuronal loss contribute to neuropathology associated with the disease outcome. The core problem we aimed to solve was understanding how JEV infection activates the unfolded protein response (UPR) in NSPCs, leading to stem cell dysfunction and death. Specifically, we focused on identifying modulators of UPR signaling pathways in NSPCs during JEV infection. By investigating these pathways, we aimed to identify potential therapeutic strategies, highlighting the potential of targeting PARP-16 to alleviate NSPC dysfunction and improve long-term recovery for patients.
How did you go about solving this problem?
Japanese encephalitis virus (JEV) is known to induce the unfolded protein response (UPR), but the upstream regulators of this pathway during infection were unclear. Our study aimed to identify such modulators in neural stem and progenitor cells (NSPCs) during JEV infection. Based on our findings, we focused on PARP-16 as a candidate modulator. To validate its role, we performed in vitro knockout experiments using siRNA targeting PARP-16. This approach confirmed PARP-16 as a key regulator of the UPR, presenting it as a potential therapeutic target to protect the NSPC pool from viral-induced prolonged ER stress.
Targeting PARP-16 may reduce NSPC dysfunction and neurological damage caused by regulating the unfolded protein response during JEV infection.
How would you explain your research outcomes (Key findings) to the non-scientific community?
Japanese Encephalitis Virus (JEV) is a harmful virus that can cause inflammation in the brain, particularly in children. When the virus infects brain cells, it triggers a process called “ER stress,” where the cell’s protein-making machinery becomes overwhelmed. This stress can lead to cell damage or even death. Our research shows that a protein called PARP-16 plays a key role in helping cells manage this stress in brain stem cells, known as neural stem/progenitor cells (NSPCs). PARP-16 helps activate series of important signals that decide whether the cells will survive or undergo damage. Understanding how PARP-16 works during JEV infection could help us develop treatments to protect NSPCs, reduce long-term brain damage, and improve the quality of life for survivors of this viral infection.
What are the potential implications of your findings for the field and society?
Japanese Encephalitis Virus (JEV) is a neurotropic virus and a leading cause of encephalitis in South-East Asia, with ~30% of infections being fatal and nearly half of survivors developing long-term neuropsychiatric disorders. In pediatric cases, JEV disrupts the function of neural stem and progenitor cells (NSPCs), impairing motor and cognitive development and delaying neurodevelopmental milestones. JEV-induced damage to NSPCs, including cell death, cycle arrest, and impaired neurogenesis, worsens neurological deficits. Our study highlights the role of Poly ADP-ribose polymerase-16 (PARP-16) in regulating the ER stress response in NSPCs during JEV infection, activating key UPR sensors like PERK and IRE-1α. Targeting PARP-16 could offer therapeutic strategies to mitigate NSPC dysfunction, improve recovery, and reduce long-term cognitive impairments, leading to better outcomes for survivors, especially in case of pediatric patients which can benefit the most .
What was the exciting moment during your research?
An exciting moment during our research was when we observed that the in vitro knockdown of PARP-16 in neural stem/progenitor cells (NSPCs) effectively prevented apoptosis induced by prolonged ER stress. This was particularly thrilling because it suggested that modulating PARP-16 could help mitigate the cellular damage caused by sustained ER stress during viral infections like JEV. While we have not yet proven that this approach would directly promote recovery, the results indicate a promising potential for preserving NSPC function and preventing neuronal loss, which could ultimately pave the way for future therapeutic strategies.
Reference: Sharma, S., Satheesan, A., Majumdar, A. et al. PARP-16 regulates the PERK and IRE-1α Mediated Unfolded Protein Response in Japanese Encephalitis Virus–Infected Neural Stem/Progenitor Cells. Mol Neurobiol (2025). https://doi.org/10.1007/s12035-025-04748-1
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