PhD Researcher · Biophysics & Bioengineering

Tharun Selvam Mahendran

State University of New York at Buffalo

My research asks how biomolecular condensates — liquid-like compartments that concentrate RNA and protein inside cells — tip from functional to pathological. Using optical tweezers, microfluidics, and bottom-up reconstitution, I showed that condensate microenvironments can enhance RNA percolation and aggregation, and that homotypic RNA clustering drives a liquid-to-solid transition at condensate cores. A parallel line of work demonstrates that decoupling phase separation from fibrillization preserves condensate biochemical activity — a strategy with direct therapeutic implications for ALS, FTD, and related neurodegenerative diseases.

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Nature Communications · 2026

Decoupling Phase Separation and Fibrillization Preserves Activity of Biomolecular Condensates

Mahendran, T.S., Singh, A., Srinivasan, S., …, Parekh, S.H., Banerjee, P.R.

We demonstrate that the conversion of protein condensates into amyloid fibrils is not an inevitable consequence of phase separation. By identifying small molecules that selectively inhibit fibrillization without disrupting condensate formation, we show that decoupling these two processes preserves the biochemical activity of the condensate — with direct implications for therapeutic targeting of condensate-driven neurodegeneration.

Nature Chemistry · 2025 · Media: EurekAlert, Phys.org

Homotypic RNA Clustering Accompanies a Liquid-to-Solid Transition Inside the Core of Multi-Component Biomolecular Condensates

Mahendran, T.S., Wadsworth, G., Singh, A.S., Gupta, R., Banerjee, P.R.

Using single-droplet biophysical methods, we reveal that repeat-expanded RNAs undergo homotypic clustering within condensate interiors, driving a liquid-to-solid phase transition at the core. This percolation transition is mechanistically distinct from bulk gelation and represents a critical checkpoint in the pathway from functional condensate to pathological aggregate.

bioRxiv Preprint · 2025

Viscoelasticity and Interface Properties of Multi-Component Condensates Govern Protein Sequestration and Suppression of Amyloid Formation

Mahendran, T.S., Bremer, A., Gui, X., …, Mittag, T., Banerjee, P.R.

We develop an optical tweezers and microfluidic platform to quantify client partitioning and efflux in multicomponent condensates. We find that condensate viscoelasticity and interfacial tension together govern how efficiently the condensate interior suppresses pathological self-assembly — revealing a physical basis for the protective role of stress granules in disease.

Frontiers in Aging Neuroscience · 2020

Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics

Mahendran, T.S., Suresh, S.N., Garimella, L., Manjithaya, R.

We show that soluble tau — prior to forming tangles — disrupts endocytic vesicle trafficking in cells, implicating pre-aggregate tau species as an early driver of neuronal dysfunction in Alzheimer's disease. Live-cell imaging reveals that tau overexpression stalls vesicle dynamics in a 4R0N isoform-specific manner.

Research Focus

RNA Phase Transitions

Characterizing the thermodynamic and kinetic drivers of RNA condensation, including repeat-expanded RNAs that drive liquid-to-solid transitions linked to ALS and FTD.

Biomolecular Condensates

Using optical tweezers, microfluidics, and single-droplet rheology to quantify how condensate microenvironments regulate client recruitment, sequestration, and pathological self-assembly.

Decoupling Phase Separation & Fibrillization

Identifying small molecules and strategies that uncouple condensate formation from amyloid fibril nucleation, preserving the functional biochemistry of condensates.

Programmable Therapeutics

Engineering condensate behavior for next-generation RNA-based biologics, oral peptide delivery, and programmable biological materials.

Selected Publications

Nature Communications · 2026

Decoupling Phase Separation and Fibrillization Preserves Activity of Biomolecular Condensates

Mahendran, T.S., Singh, A., Srinivasan, S., …, Parekh, S.H., Banerjee, P.R.

Nature Communications

Nature Chemistry · 2025

Homotypic RNA Clustering Accompanies a Liquid-to-Solid Transition Inside the Core of Multi-Component Biomolecular Condensates

Mahendran, T.S., Wadsworth, G., Singh, A.S., Gupta, R., Banerjee, P.R.

Nature Chemistry · Media: EurekAlert, Phys.org

Molecular Cell · 2025

Tunable Metastability of Condensates Reconciles Their Dual Roles in Amyloid Fibril Formation

Das, T., Zaidi, F., Farag, M., Ruff, K.M., Mahendran, T.S., …, Banerjee, P.R., Pappu, R.V., Mittag, T.

Molecular Cell · Commentary in Cell Chemical Biology

Science Advances · 2025

ASPL Couples the Assembly and Dissolution of Stress Granules: Implications for Disease

Pareek, G., Li, D., Wang, B., …, Mahendran, T.S., …, Banerjee, P.R., Kundu, M.

Science Advances

bioRxiv Preprint · 2025

Viscoelasticity and Interface Properties of Multi-Component Condensates Govern Protein Sequestration and Suppression of Amyloid Formation

Mahendran, T.S., Bremer, A., Gui, X., …, Mittag, T., Banerjee, P.R.

bioRxiv

Frontiers in Aging Neuroscience · 2020

Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics

Mahendran, T.S., Suresh, S.N., Garimella, L., Manjithaya, R.

Frontiers in Aging Neuroscience

Chemosphere · 2021

Role of Cerium Oxide Nanoparticles in Improving Oxidative Stress and Developmental Delays in Drosophila melanogaster

Sarkar, A., Mahendran, T.S., …, Sahabudeen, S.

Chemosphere

Transcription · 2021

Long Noncoding RNAs: Role and Contribution in Pancreatic Cancer

Ramya Devi, K.T., Karthik, D., Mahendran, T.S., Jaganathan, M.K., Hemdev, S.P.

Transcription

Full list → Google Scholar · PubMed · bioRxiv

About Me

Education

Ph.D. in Biophysics

State University of New York at Buffalo · Dissertation: The Balancing Act of Biomolecular Condensates in Pathological Aggregation · Supervisor: Prof. Priya R. Banerjee

Jan 2021 – May 2026 (Expected)

B.Tech. in Biotechnology

SRM University, Tamil Nadu, India · First class with distinction

Aug 2015 – May 2019

Next Position

Incoming ODBI Innovator Fellow at Princeton University, with a long-term goal of building an independent research group.

Technical Expertise

Optical Tweezers + Microfluidics Flicker Spectroscopy Live-Cell Confocal Imaging Single-Droplet Rheology Particle-Tracking Nanorheology RNA Biochemistry FPLC Protein Purification Phase Diagram Mapping Fluorescence Lifetime Imaging In Vitro Condensation Assays Python / Image Analysis Adobe Illustrator Drosophila & Mouse Models

Selected Recognition

Best Presentation Award

Buffalo RNA Society, USA

2025

Student Research Achievement Award

Biophysical Society, USA

2025

Sigma Xi Companions in Zealous Research Award

Sigma Xi Society, USA

2025

Dissertation Fellowship

State University of New York at Buffalo

2025

Presidential Fellowship

State University of New York at Buffalo

2021

Tharun Selvam Mahendran

Research Focus

Selected Publications

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