Current Position: Postdoctoral Research Associate
Affiliation: Department of Anesthesiology & Perioperative Medicine, University of Rochester Medical Center, USA
Publications:
- First Author: “Tauopathy-associated tau modifications selectively impact neurodegeneration and mitophagy in a novel C. elegans single-copy transgenic model” – Molecular Neurodegeneration (2020)
- Corresponding Author: “The Crosstalk Between Pathological Tau Phosphorylation and Mitochondrial Dysfunction as a Key to Understanding and Treating Alzheimer’s Disease” – Molecular Neurobiology (2020)
Author Interview
How would you explain your paper’s key results to the non-scientific community?
Our research is focused on Alzheimer’s disease (AD), specifically on a protein called tau. Under normal conditions, tau is essential for neurons, helping them maintain structure and function. However, when tau undergoes specific post-translational modifications (PTMs)—like phosphorylation and acetylation—it becomes toxic and leads to neuronal damage.
We used C. elegans, a tiny nematode worm, as a model. By introducing human tau into their genome and using CRISPR/Cas9 to induce disease-relevant mutations, we created a system that mimics the neurodegenerative effects seen in Alzheimer’s.
One key finding: these tau modifications severely impact mitochondrial health—a crucial energy system in cells—thus accelerating neurodegeneration.
“[…] led us to uncover novel molecular pathways and logic by which pathological tau impair neuronal shape and function.”
What are the possible consequences of these findings for your research area?
We established a mechanistic link between toxic tau and mitochondrial dysfunction, clarifying how tau contributes to neurodegeneration. We focused on PTMs like phosphorylation at Threonine 231 (T231E) and acetylation at Lysine 274/281—sites that can be targeted using immunotherapy, acetylation modulators, and kinase inhibitors. These are potential drug targets in AD therapy.
What was the exciting moment (eureka moment) during your research?
We examined mitophagy—a process cells use to clean out damaged mitochondria. Under stress (e.g., via the toxin paraquat), mitophagy normally increases. But in our tau-mutant worms, this response was blocked, leading to a dangerous buildup of damaged mitochondria. This mimics a known human brain condition called “system overload.”
We validated this with a fluorescent probe called mito-mKeima, targeted specifically to mitochondria. Seeing this mechanism mirrored in our worm model was a breakthrough moment.
What do you hope to do next?
We’re working on a CRISPR/Cas9-based approach to insert a 44-amino acid “Degron” motif into our system. This motif targets toxic tau for degradation in the presence of a plant hormone, auxin. If we succeed in degrading tau, we’ll test whether the neurodegeneration can be reversed.
In the future, we plan a dual therapy approach:
- Enhance mitochondrial health, and
- Simultaneously clear toxic tau,
using C. elegans as a platform for drug screening.
Where do you seek scientific inspiration?
My inspiration comes from my family.
- My grandfather, a civil surgeon, and
- My father, an electrical engineer with the West Bengal State Electricity Board.
Their dedication and work ethic inspired me deeply.
Also, my wife, Sree, is a huge inspiration. She is a faculty member at the University of Rochester and a senior embryologist at Strong Memorial Hospital. Her accomplishments and work ethic make me incredibly proud.
“[…] grateful to my Alma mater, Heritage Institute of Technology, Kolkata (HITK), to shape my career path and provide all the support and needs for me to pursue higher education abroad.”
How do you intend to help Indian science improve?
Whenever I visit India, I deliver talks at universities, sharing insights on pursuing a scientific career and global opportunities. I’m grateful to Heritage Institute of Technology (HITK), Kolkata, for supporting my journey.
I’ve started a HITK alumni group, organizing monthly seminars featuring alumni, faculty, and students.
I also volunteer with Freedom English Academy (FEA), mentoring students on English fluency, job interview prep, resume writing, and study abroad options—via regular Zoom sessions.
References
- Guha S, Fischer S, Johnson G.V.W., Nehrke K.
“Tauopathy-associated tau modifications selectively impact neurodegeneration and mitophagy in a novel C. elegans single-copy transgenic model”
Molecular Neurodegeneration, 15, 65 (2020)
Link - Guha S*, Johnson G.V.W., Nehrke K.
“The Crosstalk Between Pathological Tau Phosphorylation and Mitochondrial Dysfunction as a Key to Understanding and Treating Alzheimer’s Disease”
Molecular Neurobiology, 57(12) (2020)
Link
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