Browse wide-ranging research at the frontiers of neuroscience supported by Wu Tsai Neurosciences Institute grants, awards, and training fellowships.
Projects
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.
Manipulating inflammation in the aging brain to promote brain resilience
Inflammation is a hallmark of brain aging, yet the source of inflammation in the old brain — and how to eliminate it — is unknown. This team aims to provide insight on how inflammation affects the aging brain that could potentially lead to the generation of new therapies to promote brain resilience.
Mechanistic dissection and therapeutic capture of an exercise-inducible metabolite signaling pathway for brain resilience
Exercise improves cognition and protects against age-associated neurodegenerative diseases, but further research is needed to understand exactly how this occurs. This project aims to pave the way for therapeutics that can capture the benefits of exercise for promoting brain resilience.
Mutant microglia and resilience to Alzheimer’s disease
This project aims to identify how mutant peripheral immune cells that invade the brain might actually reduce Alzheimer’s disease risk. The research will explore how to mimic these cells’ resilience-promoting effects to design new Alzheimer’s therapies.
From gut to brain: reprogramming peripheral macrophages at the intestinal barrier to prevent age-associated inflammation and cognitive decline
This team will investigate whether a decline in intestinal immune cell metabolism drives age-related inflammation and cognitive decline. By replacing aged intestinal macrophages with metabolically healthy ones, they hope to develop a novel approach to enhance cognitive resilience.
Unleashing engineered T cells as disease sensors and therapeutic actuators for neurodegenerative disease
This project will explore whether amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) result from immune cells attacking altered neurons. The team aims to pioneer the use of engineered immune cells as therapies for neurodegenerative disorders.
Role of Proteostasis and Organelle Homeostasis in Brain Resilience during Aging
This team aims to define how and why protein production breaks down in aging cells, leading to disease. This research may lead to new diagnostic and therapeutic approaches against neurodegenerative diseases and potentially aging itself.