Neural modulation and the control of skeletal health and brain/skeletal signaling after injury
Research in the Elefteriou laboratory indicates that sympathetic input to bone cells is critical for growth and maintenance. Further, there is an evolving understanding of a network of brain-stem neurokines that promote bone remodeling and a reciprocal network of bone-derived hormones that impact brain health. This project seeks to model how motor and/or autonomic neuromodulation effects bone remodeling in the brain and bone hormone network. The Horner and Elefteriou laboratories will collaborate to measure bone marrow activation, bone signaling, and central neural signals that change due to neuromodulation in a model of spinal cord injury.
Biomimetic nanoparticles to promote neural connectivity
Defining the functional consequence of astrocyte activity upon neural networks
In parallel, astrocyte states will be manipulated, using transgenic mouse models, and similar physiological measurements will be conducted (Deneen Laboratory). Astrocytes in both models will be profiled with RNA sequencing to uncover potential mechanisms underlying astrocyte activity-induced neuronal communication. It is expected that high priority intercellular signaling pathways will be identified to translate into preclinical testing regarding restoring normative function that is dysregulated in inflammatory environments post-injury and post-disease.
Manipulation of RNA compartmentalization to facilitate regenerative responses
Top candidates will be manipulated in mouse spinal cord injury models to assess their function in promoting axon regeneration (Horner Laboratory). Data gained from this systematic analysis and functional validation will offer new opportunities for the development of effective RNA therapy and treatment strategies for spinal cord and brain injury.
Spinal neuromodulation and recovery of bladder control after injury
This project will combine advanced neuroimaging approaches, urodynamics, and non-invasive spinal neuromodulation to identify the patterns of supraspinal-spinal activation and connectivity during the initiation, maintenance, and completion of voiding (or attempt of voiding) in intact, or paralyzed due to spinal cord injury and multiple sclerosis, subjects and to elucidate the neuromodulatory mechanisms of spinal stimulation on bladder control. The central hypothesis is that neural activation profiles can be used to selectively target specific regions within the central nervous system using spinal neuromodulation. Thus, the spinal and supraspinal effects of transcutaneous spinal stimulation on voiding will be examined.
Modulating the gut microbiome to reduce neurodegeneration
The laboratory of Dr. Jeannie Chin is devoted to characterizing patterns of brain activity in mice and correlated neuronal activity with performance in behavioral paradigms that test different aspects of memory and cognition, especially using animal models of Alzheimer's disease (AD). Furthermore, the relationship between the microbiome and the development of cognitive impairment in dementia or the development of AD is unknown. This project will deplete the microbiome in AD animals and will restore it with the pre-AD microbiome. Specifically, the Villapol and Chin laboratories will identify the link between the modulation of the microbiome in AD mice and brain connectivity, amyloid beta accumulation, and memory impairment, with the goal of identifying novel treatments to restore cognition and behavior in neurodegenerative diseases.
Sajedeh Nasr, PhD
Sajedeh Nasr Esfahani, PhD was selected as the inaugural NIH-funded postdoctoral fellow in our NeuralCODR postdoctoral training program for her project developing cell-based therapeutics to improve neuron reconnectivity after various nervous system injuries. As a NeuralCODR trainee, her primary mentor is Robert C. Krencik, PhD (Neural Development and Tools), her secondary mentor is Mary C. "Cindy" Farach-Carson, PhD (Neural Innervation and Organ Engineering), and her clinical mentor is Amir Faraji, MD, PhD. Her project titled “Generating and Validating Astrocyte-Inspired Functionalized Hydrogels to Promote Synaptic Regeneration” addresses the lack of bioengineering strategies to promote neuroregeneration in the human central and peripheral nervous system. Dr. Nasr is developing methods to use alginate hydrogels to stably encapsulate human astrocytes and permit the secretion of proteins for the repair of either the injured central nervous system or the injured peripheral nervous system.
Laura Montier, PhD
Laura Montier's current work examines changes in mitochondrial regulation in response to therapeutic stimulation after spinal cord injury. Her primary mentor is Philip Horner, PhD (Nervous System and Peripheral Organ Disorders). Her secondary mentor is Shu-hsia Chen, PhD (Nervous System and Peripheral Organ Disorders) and her clinical mentor is Dimitry Sayenko, MD, PhD. Dr. Montier's project uses neurostimulation after injury of the spinal cord to overcome the harmful effects of neuroinflammation and restore axonal projections and synapse organization to regain lost motor skill function. Her study aims to address the timing of mitochondrial turnover after neurostimulation to meet the increased energy demands for neuronal growth in an inflammatory environment.
Sirena Soriano, PhD
Sirena Soriano is investigating the role that the gut microbiota plays in the link between traumatic brain injury and Alzheimer's disease. Dr. Soriano's primary mentor is Sonia Villapol, PhD (Nervous System and Peripheral Organ Disorders). Her secondary mentor is Muralidhar Hegde, PhD (Nervous System and Peripheral Organ Disorders) and her clinical mentor is Eamonn Quigley, MD. Her research aims to restore the gut microbiota in a mouse model of Alzheimer's disease in order to reduce neurodegeneration that occurs following a traumatic brain injury. The results from her research will provide the foundation for pursuing novel therapies based in manipulating the microbiota for Alzheimer's disease-related pathologies consequence of traumatic brain injury.
Matthew Hogan, PhD
Caroline Cvetkovic, PhD
Betsy Salazar, PhD