Research

Research in the Ramakrishnan Lab aims to uncover how disruptions in vesicular communication networks drive diabetes and neurodegeneration. Our current research projects include the molecular pathology of dense core vesicle secretion for neuropeptides and insulin, the complex dysregulation of neuron-islet communication in diabetes, and pathophysiological roles of extracellular vesicles. Our approach is multi-faceted and highly interdisciplinary, operating at the intersection of experimental pathology and nanobiology. To understand how these communication networks fail at the cellular and tissue levels, we rely on advanced molecular, biochemical, and high-resolution imaging techniques to track aberrant vesicle fusion and exocytosis in real-time. Uniquely, our biological investigations are driven by the development of cutting-edge lab-on-a-chip platforms, empowering us to manipulate, isolate, and analyze pathological cellular communication with unprecedented spatiotemporal precision.

  • Protein Aggregates

Pathological Protein Aggregation and Secretory Dysfunction

The accumulation of pathological protein aggregates fundamentally disrupts cellular communication. Our lab investigates how these misfolded proteins physically and biochemically impair the tightly regulated machinery of dense core vesicle (DCV) fusion. By examining the precise interactions between pathogenic aggregates and the exocytotic proteins at the nanoscale, our lab is decoding how early-stage aggregation affects exocytosis and neuropeptide release, blunts cellular signaling, and ultimately drives cellular secretion.

  • Neuon-Islet Signaling

Neuron-Islet Communication & Neuro-Metabolic Axis

Pancreatic islets are densely innervated by peripheral nerves, forming a bidirectional communication network that regulates systemic glucose metabolism. Dissecting how neural inputs modulate islet hormone release and how islet-derived signals influence local nerve activity remains a major challenge in endocrine biology.

Our lab develops co-culture models and functional imaging assays to record live intercellular signaling between neurons and pancreatic islet cells. By resolving these neuro-endocrine circuits at cellular resolution, we investigate how circuit disruption contributes to metabolic disorders like diabetes.

  • Lab-on-Chip Engineering

Lab-on-a-Chip Engineering & Computational Pipelines

Our biological inquiries are continuously driven by the development of microfluidic lab-on-a-chip technologies, enabling high-throughput, precision manipulation of cells and extracellular vesicles.

To process the massive datasets generated by these platforms, we build robust computational architectures. Utilizing custom Python and MATLAB scripts, we automate image masking, batch processing, and quantitative data analysis, seamlessly bridging physical hardware with automated digital discovery.