Mariajose Metcalfe-Lilliewood

Spinal cord injuries (SCI) disrupt ascending and descending pathways in the spinal cord, compromising motor control of muscles below the site of injury and sensory signals that go to the brain. Damage to the spinal cord doesn’t heal because the injured nerve cells fail to regenerate. Regrowth of injured axons is hindered by the lack of growth capacity of adult neurons and by external inhibitory factors present in the injury site. As such, axonal regeneration is an unsolved problem in neuroscience. My research is focused on the  development of combinatorial strategies to promote axonal growth after SCI using viral vector approaches (AAV). On April 2020, I was awarded an NIH supplement to promote re-entry into Biomedical Research Careers. As part of this effort, I have designed and tested retrogradely transported vectors to study neuron-intrinsic growth regulators. These vectors can be injected in the spinal cord and transported retrogradely to cells of origin of different pathways to achieve recovery of function of more complex behaviors and functions. To address the contribution of extrinsic growth factors in the injury site, I have designed AAVs to degrade molecules that impede axonal growth after injury. Having the same AAVs express different cargos make combinatorial strategies more translational. Also, I am developing a novel rapid and sensitive approach for screening viral transgene expression in vivo where individual animals can be tested repeatedly to assess transgene expression at multiple timepoints. This state-of-the-art technique will provide a valuable tool to accelerate AAV-based research that can be used by any group studying vector-based delivery of cargos in the spinal cord or other brain regions. My research is creative, innovative, and significant since it will uncover mechanisms of spinal cord regeneration that may inform therapeutic strategies to promote recovery in individuals with spinal cord injury.