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The nervous system depends on the precise coordination of diverse cell types and molecular interactions to establish and maintain functional neural circuits. Disruptions in these tightly regulated processes can alter neuronal connectivity and cellular communication, contributing to a wide range of neurodevelopmental and neurodegenerative disorders. Understanding the fundamental mechanisms that govern the correct formation, maintenance, and remodeling of these neuronal connections is therefore essential for understanding both normal brain function and disease. Through the NeuroWeave framework, our research investigates how dynamic cell-surface signaling and neuron-glia interactions shape neural connections, with the long-term goal of uncovering mechanisms that may guide future therapeutic strategies.
We use cell-surface labeling and surface biotinylation approaches to capture dynamic changes in the cell-surface proteome under defined experimental conditions. Candidate molecules identified through these analyses are functionally validated using a range of cellular and developmental assays, including axon growth and guidance, neurite outgrowth, and circuit-related phenotypes. These studies are performed across multiple model systems, including mouse embryonic primary neurons, explant cultures, neurospheres, and human iPSC-derived neuronal models, enabling us to link molecular mechanisms with functional outcomes across developmental contexts. (Image was generated by Dr. Gorla at Bashaw Lab at the University of Pennsylvania,, Philadelphia, USA)
Project 1: Decoding Cell Surface Dynamics in Neural Development
Project 1: Decoding Cell Surface Dynamics in Neural Development
Commissural neurons rely on highly dynamic cell-surface axon guidance receptors to sense and respond to their surrounding environment during development. Small changes in the composition, localization, and turnover of these receptors can profoundly influence how neurons establish precise connections. We investigate how neuronal surface proteomes are dynamically regulated to control guidance decisions and circuit assembly. Using biochemistry, proteomic approaches, live-cell imaging, and human iPSC-derived neuronal systems, our goal is to uncover molecular mechanisms that orchestrate neural wiring and determine how their disruption contributes to developmental disorders.
We use hiPSC-derived neurons and microglia to study how neuron-glia surface signaling controls synaptic remodeling and how its disruption contributes to neurological disease. (Image was generated by Dr. Gorla at Annette Lab at MDC, Berlin, Germany)
Project 2: Neuron-Glia Communication in Development and Disease
Project 2: Neuron-Glia Communication in Development and Disease
Neural circuits are shaped not only by neurons but also by dynamic interactions with glial cells that actively regulate connectivity and tissue homeostasis. We investigate how the cell-surface proteomes of neurons and microglia coordinate intercellular communication to control synaptic remodeling, phagocytosis, and circuit integrity during development and neuroinflammatory conditions. By integrating advanced imaging, molecular and proteomic approaches, and stem-cell-based neuronal and glial models, we seek to uncover how neuron-glia surface signaling maintains healthy brain function and how its disruption contributes to neurological disease.
Mouse embryonic dorsal spinal cord explant with neurons projecting from the cell bodies. (Image was generated by Dr. Gorla and Dr. Karina at Bashaw Lab at the University of Pennsylvania, Philadelphia, USA)
Project 3: Molecular Mechanisms Linking Development and Neurodegeneration
Project 3: Molecular Mechanisms Linking Development and Neurodegeneration
Molecular pathways that guide neural development are frequently reused later in life to regulate cellular homeostasis, inflammatory signaling, and neuronal survival. We investigate how ubiquitin adaptor proteins, classically known for their roles in neurodevelopmental regulation, are used in the adult nervous system and whether their regulatory mechanisms and signaling functions are distinctly maintained or reprogrammed under neuroinflammatory and neurodegenerative conditions. Through genetic manipulation, biochemical approaches, and human and mouse model systems, we aim to uncover molecular principles that connect developmental signaling networks with mechanisms of neurodegeneration and identify pathways with therapeutic potential.
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