Neuronal survival and proper function depends on cell-cell communication mediated by ligand-receptor mechanisms. During neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), there is considerable synapse/neuromuscular junction (NMJ) disruption and neuronal cell death. It is non-autonomous processes involve interactions between the neurons to its diverse extracellular microenvironments. The molecular basis for this neuronal dysfunction and death is still poorly understood. One possible reason for it is alterations in the nature, directed movement and spatial localization of vital extra and intra cellular signals.
The long-term research goal of the lab is to understand the vital molecular communications mechanisms between the neurons to its environment. More specifically we seek to understand the role that retrograde signaling plays in:
- Neuronal survival
- Synapse stability
We believe that our research will generate novel insights into neurodegenerative mechanisms and ultimately, provide a molecular basis for new drugs as well as delivery methods to treat a range of neurodegenerative diseases.
Axonal transport and Neurodegeneration
One of the fundamental tasks of a cell in order to control its fate and function is to create a dynamic system of spatial specificity and fidelity of signaling pathways that can respond to internal or external changes over space and time. Cell signal must be at the right place and at the right time, alterations in its specific localization may lead to dysfunction and death. In the case of neurons that have long processes, this spatial specificity task is daunting. The neuron regulates this process by protein trafficking mechanisms. Consequently, the precise targeting and delivery of cellular signals to specific, distinct sub-cellular compartments in neurons is largely achieved via axonal transport mechanisms.
Axonal transport is the cellular process of moving proteins, organelles, vesicles, RNA and other cellular factors to (retrograde) and from (anterograde) the neuron cell body. Axonal transportis is vital to maintain neuronal function and survival. The molecular motor kinesin drives anterograde transport from the cell body outward along the axon. The dynein/dynactin complex drives retrograde axonal transport, moving signaling molecules like neurotrophins from cell periphery to cell body. Alterations in axonal transport have shown to lead to neurodegenerative diseases.
Our current efforts are focused on studying molecular mechanisms of:
- Axonal transport
- Communication between the neuron and its environments
- Local protein synthesis in Axons and NMJs
- Retrograde signaling and cell survival
- Synapse stability and maintenenance
- RNA transport in health and disease
- Receptors spatial targeting
- Virus trafficking
- Membrane dynamics
- Microfluidic system, single molecule and nanotechnology