Nance Lab
Disease-Directed Engineering
Research Overview
To dive deeper or read about active project areas, head to our Research Thrusts Page!
Develop tunable, developmentally appropriate models of brain disease
We have pioneered the use of organotypic whole hemisphere (OWH) brain slices and demonstrated the use of these slices in (1) studying inflammation, oxidative stress, cell death, and metabolic failure and in (2) screening promising therapeutics for treatment of these pathological processes in the brain. We have cultured whole hemisphere brain slices from a range of species, including rat, ferret, mouse, rabbit, and OR-obtained human samples, and can study donor age, sex-dependent and brain-region dependent responses to various stimuli. We have published a range of molecular, cellular, and functional assessments in slices to study changes in the cellular and extracellular space and these slice platforms allow high throughput live tissue imaging in the acute and chronic windows after injury, or to study aspects of neurodevelopment, while retaining the 3D cytoarchitecture and in vivo physiological function of brain cells. In addition, microfluidic model systems are effective in representing how the blood-brain barrier (BBB) functions in response to stimuli by enabling multiple cell types to engage in crosstalk in a physiologically relevant 3-dimentional architecture in the presence of flow.
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Learn more about active project areas in slice model and microfluidic model development!
Design principles for nanotherapeutic delivery to the brain
We have identified general design principles for engineering therapeutics for delivery to the brain, with the goal that the design principles are adaptable to any nanoparticle system. We have shown that nanoparticles of sizes ranging from 10s of nanometers to larger than 100mm can overcome the BBB when it is impaired, or when the BBB is intact, by leveraging receptor transports , osmotically induced permeability, or with external non-invasive BBB permeability strategies. Our growing evidence also demonstrates that particles reaching the brain from systemic administration should have near-neutral or anionic net surface charge, and that cationic surface charges on nanoparticles result an inability to cross even in an impaired BBB. Within the brain parenchyma, we have shown that the estimated upper limit for rapid nanoparticle transport is around 120nm, with potential for larger sizes based on results by us and others that show effective spaces in the brain can range up to 1µm in size. We have also identified the importance of surface charge and functionalization in increasing nanoparticle penetration in the brain, with neutral or anionic net surface charges imparted by hydroxyl, methoxy, or carboxyl groups driving maximum diffusive ability in the brain. Thus far, we have applied these general design criteria to nanoparticles made from polymer, quantum dot, cellulose, peptoid, dendrimer, or extracellular vesicle materials.
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Learn more about active project areas in establishing design principles for delivery to the brain!
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Evaluating neurotherapeutics for improving brain health in newborns and children
Therapies intended for use in children can take up to 7 years longer to go from the first clinical trial in adults to the first trial in children; often, many approved adult therapeutics are used off-label for children. There is a significant gap in technological development for the neonatal and pediatric populations, particularly in technology that focuses on improving therapeutic outcomes for children and newborns with a range of conditions. Our research seeks to develop and evaluate therapeutic delivery systems for newborns and children, who have unique physiologies compared to adults. We focus specifically on engineering therapeutics that mitigate or attenuate ongoing injury in the brain, with the goal of improving neurological function and quality of life across the lifespan.
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Learn more about active project areas in screening and evaluating therapies for treating brain disease!
Research Tools
Data Science & Machine Learning
Biological imaging of brain tissue produces large, complex datasets that are difficult to parse and analyze manually. Development of open source, scientific software improves the speed and reproducibility of analyzing these datasets, while modern data science methods can be used to uncover patterns and connections that would otherwise be hidden.
Image & Image Analysis
Immunofluorescent imaging is one of the most common ways
to acquire cell images and quantify cell features. We use live and fixed imaging of brain cells, nanoparticles, and subcellular compartments in cells. We also analyze cellular responses via imaging, which requires transparent, reproducible image processing practices.
Multiple Particle Tracking
Multiple particle tracking (MPT) is a powerful imaging tool with high spatial and temporal resolution. It is a microrheological technique that simultaneously tracks 100s of probe particles. We apply MPT to nanoparticle probes in living brain tissue to measure spatial microrheology in different brain regions and brain conditions.
Research Training
Training in scientific research to support the current and next generation of STEM leaders is core to who we are and what we do.
We embrace living practices for mentoring trainees with a range of lived experiences and identities. To learn more about our mentoring practices and resources, head to our training page.
