Following a traumatic brain or spinal cord injury, there is limited nerve regeneration, and patients are often left with devastating and long-lasting neurological impairments.
Researchers at Mount Sinai are actively studying molecular mechanisms by which adult neurons can be triggered into an active growth state to regenerate axons and reestablish lost connections in order to restore function. Our scientists are also engaged in innovative research using stem cells to repair and/or replace dead or affected cells (cell replacement therapy).
Areas of Research
Our research in brain and spinal cord injury is focused on a number of different areas.
Transcriptional Control of Axon Growth and Regeneration
The molecular mechanisms that control the capability of adult neurons to regenerate axons are an important unsolved question in neurobiology. Neurons of the mammalian central nervous system (CNS) regenerate axons minimally after injury. Failure of CNS-axon regeneration is attributed to an inhibitory environment and the age-related decline of the intrinsic potential of axons to grow. In contrast to CNS neurons, injured neurons in the peripheral nervous system (PNS) can regenerate axons, but this requires both activation of a neuronal pro-regenerative transcription program and glial cell plasticity. Our scientists are studying the close collaboration between regeneration-associated transcription factors and epigenetic machinery that modifies chromatin landscape in adult neurons to activate a growth state. Researchers also are exploring the molecular mechanisms underlying glial cell plasticity after injury. We hope that insights gained in this research will help to identify molecular targets to promote axon regeneration after an injury to the central nervous system.
Neural Stem Cells and Neural Repair after CNS Injury
Functional recovery after an injury to the central nervous system hinges on axonal sprouting of surviving neurons and plasticity of cortical circuits to reconstruct connectivity. Adult neural stem cells (NSCs) play an important role in modulating injury response after injury. In addition, transplantation of NSCs or reprogramming stem cells holds tremendous promise as cell replacement therapy. Our scientists are investigating novel molecular players in mediating axonal sprouting and cortical circuits plasticity after a CNS injury. They employ a variety of tools including mouse genetics, NSC biology, stroke models, imaging, and tissue-engineering techniques.
Scientists involved: Thomas N. Bryce, Marcel J. Dijkers, Gregory A. Elder, Colette Seter Elliott, Roland Friedel, Samuel E. Gandy, Wayne A. Gordon, Maria Kajankova, Allan J. Kozlowski, Jason W. Krellman, William Lu, Nicole Murray, Kristen Dams O'Connor, Kristjan T. Ragnarsson, Hongyan Zou