RESEARCH



Traumatic brain injury (TBI) is a growing global health challenge, with more than 20 million new cases reported worldwide in 2021 and long-term disability affecting tens of millions. In India alone, an estimated one million people sustain a TBI each year, with roughly 200,000 deaths, while the downstream risk of chronic traumatic encephalopathy (CTE) driven by repetitive head impacts and tau pathology remains poorly understood. Our laboratory investigates how physical forces are transduced across biological scales - from organ-level impact mechanics to mesoscale protein aggregation - to uncover the physical principles that drive progressive neuropathology following repeated traumatic brain injuries (TBIs). Our research is organized into three interconnected verticals that span the relevant length-scales.

MESOSCALE & MOLECULAR TAU BIOPHYSICS

Tissue scale brain injury modeling and translation
Protein-protein interactions with active post-translational modifications can explain the formation of membraneless protein condensates

Our research seeks to uncover the physical principles that govern how tau proteins condense, transform, and misfold into pathological aggregates. We develop mechanochemical models that couple tau phosphorylation and hyperphosphorylation dynamics with intermolecular interactions and ionic environments to explain how normal condensates evolve into fibrillar tangles seen in CTE and related tauopathies. By integrating quantitative modeling with collaborative experimental validation, we aim to reveal how non-equilibrium biochemical regulation drives mesoscale organization and pathological transitions. This framework aspires to identify new physical biomarkers and intervention strategies targeting early stages of neurodegeneration.


CELL SCALE CYTOSKELETAL MECHANICS

Tissue scale brain injury modeling and translation
Active microtubules network reorganization in response to MAP-tau dysregulation can explain chronic neurodegeneration related injury predisposition.

We investigate how tau phosphorylation dynamics orchestrate the self-organization of the axonal cytoskeleton. Building on our models of tau phase separation, we explore how optimally phosphorylated tau drives microtubule growth, alignment, and cross-linking to form mechanically resilient axonal bundles. By coupling biochemical regulation with cytoskeletal force transmission, our work bridges molecular kinetics and cellular mechanics to reveal how structure and stability emerge from active processes. Extending this framework, we aim to uncover how hyperphosphorylation and injury disrupt cytoskeletal architecture, offering new insights into the mechanical fragility and progressive degeneration of axons following traumatic brain injury.


TISSUE SCALE BRAIN INJURY SIMULATIONS

Tissue scale brain injury modeling and translation
Tissue-scale brain injury simulations must be guided by meso- and cell-scale neurodegeneration to gain chronic insights into repeated traumatic brain injuries.

Our long-term goal is to bridge cellular pathology with brain-scale mechanics to better understand the progression of traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE). While current TBI models largely focus on stress and strain distribution, we seek to integrate the secondary biochemical and neurodegenerative effects emerging from tau dysregulation and cytoskeletal disruption. By coupling multi-scale mechanochemical models—from axonal dynamics to tissue-level deformation—we aim to uncover how local cellular injury cascades into global brain dysfunction. This framework aspires to redefine predictive modeling of brain injury by incorporating the feedback between neurons, glial cells, and the surrounding tissue microenvironment.