Browse wide-ranging research at the frontiers of neuroscience supported by Wu Tsai Neurosciences Institute grants, awards, and training fellowships.
Projects
Investigating severe traumatic brain injury using a novel human CSF cell-free mRNA gene panel
This team aims to be the first to study the cellular and molecular impact of traumatic brain injury by studying genetic material in human cerebrospinal fluid. This will help clinicians and researchers ID markers of brain resilience after injury, and ultimately improve treatment for severe TBI.
Rejuvenating sleep to enhance brain resilience with age
Sleep is a critical behavioral state that fulfills essential needs for health, including clearing waste products (e.g., protein aggregates) from the brain. But sleep is not everlasting. As humans age, sleep quality strikingly deteriorates, and this decline is associated with dementias (e.g., Alzheimer’s disease).
Elucidating the role of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
With an aging population, neurodegenerative disorders contribute increasingly to our global health burden with no cure or effective treatments. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two neurodegenerative disorders that are distinct in clinical presentation (ALS impairs movement/breathing, whereas FTD impairs behavior/cognition).
Neuron-glia interactions in regulating protein aggregation in human cell models.
There is one characteristic of all neurodegenerative diseases: the accumulation and aggregation of abnormal proteins in the patient’s brain. These aggregations are thought to induce neuronal cell death and brain degeneration.
The origin of neurodegeneration: insight from a unique colonial chordate
With an aging population, neurodegenerative disorders contribute increasingly to our global health burden with no cure or effective treatments. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two neurodegenerative disorders that are distinct in clinical presentation (ALS impairs movement/breathing, whereas FTD impairs behavior/cognition).
Determining the role of circadian transcriptional control in myelin-forming precursors in neurodegeneration
The causes of neurodegenerative disorders like multiple sclerosis or Alzheimer’s disease are incompletely understood, hindering our ability to gain precise diagnoses and design effective therapeutics. Understanding how the circadian rhythms regulate myelin-forming precursors will impart unique insights into normal and aberrant myelination and will have a positive impact on developing therapeutic strategies to restructure myelin.
High-resolution profiling of Alzheimer’s brain resilience
Resilience to Alzheimer’s disease (RAD) describes those rare individuals who exhibit normal cognitive function
while harboring a high disease burden. Better understanding of the mechanisms that confer protection against
cognitive decline despite high-level AD pathology offers potential therapeutic insights for preventing dementia in AD. Recent advances in the field provide a unique opportunity to explore the spatial distribution of molecules in the human brain at an unprecedented level of detail.
TREM1 in peripheral myeloid cells exacerbates cognitive decline in aging and Alzheimer's disease
Alzheimer’s disease (AD) is the sixth leading cause of death in the United States and there is a tremendous need for improved therapeutic strategies to treat this prevalent neurodegenerative disease. A devastating symptom of AD is progressive memory loss; this particular disease feature has proven difficult to treat. However, research has begun to unravel novel drivers of AD, including the important role the body’s immune system plays in promoting memory loss.
Evaluating the immunomodulatory role of circular RNAs in microglia
Neuroinflammation is common in several neurodegenerative diseases, with brain immune cells, specifically
microglia, being a main driver of the inflammatory process. Understanding what triggers microglial activation and its pathways will lead to a better knowledge of inflammatory mechanisms involved in neurodegenerative disease pathology. Circular RNAs (circRNAs) have been studied extensively in the peripheral immune system due to their ability to induce innate immune responses.
Neural mechanisms of episodic memory resilience in longitudinal aging brains
Maintaining the health and function of the aging brain is crucial to improving the quality of older people’s lives and reducing societal burden. Aging is often accompanied by a decline in memory for life events (episodic memory), especially in those at risk for Alzheimer’s disease (AD). Yet some at-risk individual’s manage to maintain memory function, which raises important questions about the brain mechanisms that underly memory resilience.
Sleep and neuronal energy management in neurodegeneration
Sleep is critical for brain function in many animals, and chronic disruptions in sleep patterns are strongly linked to the emergence of neurodegenerative diseases like Alzheimer’s and Parkinson’s. When animals sleep, neural
activity and brain metabolism change dramatically; however, we do not know what the molecular functions of
sleep are in the brain, nor do we know how these processes are linked to brain health.
Predicting and promoting resilient brain aging trajectories
Using new animal models such as the African killifish, this team aims to develop approaches to predict individual brain aging trajectories early in life based on behaviors that can be modulated to promote healthy memory, executive function and processing speed as well as counter dementia.
Resilience to Synaptic Impairments in Neurodegenerative Disorders
This team will explore the idea that neurotoxic protein aggregates seen in neurodegenerative disorders act at the synaptic connections between cells, and that resilience against these disorders may come from natural synapse-supporting factors that could be transformed into new forms of therapy.
Preserving motor engrams in Parkinson's disease: Neural circuit and transcriptomic studies and strategies for resilient motor control
This team aims to better understand how Parkinson's disease attacks the brain's basic motor programs and to spawn novel therapies against the disease using gene-editing technology.
Mitochondrial DNA and Brain Resilience
This team proposes the first comprehensive study of how mitochondrial DNA is related to cognitive function and susceptibility to dementia in a diverse population of over 11,000 adults. The outcomes of this study will provide insight into possible racial disparities in brain health.
Sleep circuits in neurodegenerative disease and aging
This team plans to study whether changes in neurons in the midbrain that regulate sleep, wakefulness, and immunity could contribute to aging and neurodegeneration. If successful, this information could rescue deficits in sleep and restore a normal immune profile.
Defining the Subcellular Biology of Brain Aging and Neurodegeneration
This team plans to map how age-related dysfunction of cellular waste disposal in lysosomes could lead to neurodegenerative diseases, potentially laying the foundation for a map of organelle function in the brain.
Unlocking brain resilience with HDAC inhibition
This team aims to define a network of genes that contribute to stress resistance in neurons and identify how it could be activated to enhance brain resilience and protect against neurodegenerative disease.
Endocannabinoid metabolism as a driver of brain aging
This team aims to discover whether the brain’s endocannabinoid system is dysregulated during aging, triggering inflammation via molecules called prostaglandins. If so, a drug that decouples these systems might restore a youthful brain state and rescue cognitive function.
Characterizing the Genetic Architecture of Neuropathology with Machine Learning
This team will study the brains of individuals who lived past ninety with their cognitive function intact, using advanced tissue imaging and computer science to understand mechanisms of resilience that could slow neurodegeneration and preserve brain health.