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.
Structural and mechanistic analysis of the protein-protein interface between ABCA1 and ApoE as a potential therapeutic target for Alzheimer’s Disease
We propose a new line of research whose goal is to examine the druggability of a protein-protein interface involving ApoE, an apolipoprotein whose gene variants represent the strongest genetic risk factor for AD.
Dissecting mechanisms of gut-brain communication in Parkinson’s Disease
People with Parkinson’s Disease (PD) have different types of bacteria in their guts compared to people without neurological diseases. We will study which gut bacteria for people with PD to gain a better understanding of how gut bacteria contribute to inflammation in the body and in the brain or people with this condition.
Novel ketone-derived anticonvulsant agents for the treatment of childhood refractory epilepsy
We propose to apply mass spectrometry techniques to measure BHB-Phe and other KD metabolites in children undergoing KD for refractory epilepsy at Stanford. Further, in a mouse model of refractory genetic epilepsy, we will compare targeted BHB-Phe treatment to full KD treatment using transcriptomics, EEG assessment of seizures and cognitive testing.
Life-long, minimally invasive, and multiplex transcriptional profiling of the cerebellum
Why do all our brains mature and age in different ways, leading to different cognitive and behavioral outcomes? We envision a novel method that “copies” the information from the RNAs made by the neurons to sensor RNAs we artificially introduce into live animals.
Use of gut-brain electrophysiology to study interoception in eating disorders
In this study, we aim to (i) perform a feasibility study to determine the acceptance and feasibility of performing such recordings in the AN and ARFID eating disorders population and (ii) test the hypothesis that the electrophysiologic monitoring of the brain and stomach is associated with a clinically validated behavioral measure of interoception involving water distention of the stomach.
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.
In vivo selection for gene mutations that counteract photoreceptor degeneration
Massively parallel microwire arrays for deep brain stimulation
Brain mechanisms of spatial reasoning in mathematics
Creating an advanced transgenic animal model of autism
Autism is a highly genetic developmental brain disorder which is characterized by social impairments. Autism affects 1 in 68 US children, with an annual cost in the US of $250 billion dollars. Unfortunately, the basic biology of autism remains poorly understood.