Browse wide-ranging research at the frontiers of neuroscience supported by Wu Tsai Neurosciences Institute grants, awards, and training fellowships.
Projects
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.
Small molecule ion channel modulator to treat acute episodes of peripheral vertigo
This team is developing a small molecule that targets a voltage-gated ion channel within the inner ear for the symptomatic relief of peripheral vertigo attacks. They will use their Neuroscience:Translate award to further develop this molecule to restore normal function and improve activities of daily living for patients experiencing peripheral vertigo.
Multifunctional vascular-like electronics for integration and monitoring of human neural organoids
This study will introduce a vascular-like electronic system that merges seamlessly with neural organoids,
establishing an integrated vascular-electronic-neural network. This envisaged platform holds the promise of heralding a transformative phase in the evolution of human neural organoid research and elucidating the
fundamental understanding on the roles of oxygen and nutrient perfusion during neural development.
Neuronal innervation dynamics in uterine function and maternal age-associated miscarriage
This proposal addresses three interconnected, yet independent aims focused on the neural mechanisms implicated in age-associated miscarriages. First, the proposal aims to construct a comprehensive neuro-uterine atlas delineating neuronal subtypes innervating the uterus, elucidating how innervation patterns and transcriptome profiles evolve with age. Second, the proposal aims to implement cutting-edge tissue clearing techniques on extracted uteri to discern alterations in uterine innervation patterns and signaling across the rodent estrous cycle and the first trimester of pregnancy.
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.
Creating a pharmacologic stroke recovery therapy
This team has identified a promising protein-based therapeutic to improve stroke recovery. The team will use the Neuroscience:Translate award to identify key components of this protein to maximize its therapeutic potential for stroke treatments.
Clinical translation of a new PET radiotracer for mapping innate immune activation in multiple sclerosis and other neurodegenerative diseases
This team recently identified a selective biomarker of inflammation-promoting immune cells in the central nervous system. They will use their Neuroscience:Translate award to develop non-invasive molecular imaging strategies to distinguish between harmful (pro-inflammatory) and helpful (anti-inflammatory) immune cells in patients with Multiple sclerosis (MS).
Assessing the feasibility of an autologous cell/gel therapy for spinal cord injury
This team has developed a new therapy for patients with spinal cord injury, involving injection into the spinal cord of patient-derived stem cells within an engineered protective gel. They will use their Neuroscience:Translate award to further test and develop this novel therapy in preparation for first-in-human clinical trials.
Targeting mitochondria in glioblastoma
This team recently discovered that a small molecule they had originally developed to treat Parkinson’s disease can also reduce the volume of glioblastoma tumors – the most common form of aggressive brain tumor — by targeting the mitochondrial protein Miro1. They will use their Neuroscience:Translate award to study the mechanisms of the compound’s anti-tumor action and prepare to apply for investigational-new-drug status to move this discovery toward the clinic.
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.
How do early life experiences shape the neural underpinnings of caregiver olfactory recognition?
The ability of an infant to distinguish caregivers from strangers is fundamental for survival early in life. Across
many taxa, newborns use olfactory cues to recognize caregivers. Caregiver odors induce proximity-seeking
behavior and alleviate stress in neonatal mammals, including humans. Since all altricial animals rely on parental
care for survival and children with developmental disorders (e.g., fragile X syndrome and autism) often have
deficits in the olfactory system, it is essential to understand the mechanisms for linking caregiver odors with
affiliative behavior.
Interrogating the effects of serotonin and dopamine on neural activity in the nucleus accumbens during aggression
Studying the brain circuits involved in aggression will help us tackle big social issues like hate crimes, antisocial
behavior, and violence. Imagine if we could better understand why some people act aggressively towards
others—we could use this knowledge to protect people from harm and create a world where everyone feels safe. Chemicals in our brain, such as dopamine and serotonin, affect neural activity to modulate behavior. When we experience something rewarding, like having good food or meeting friends, dopamine is released in the brain.
Interpretable machine learning to decipher gene regulation in brain development and disruption in disease
Brain development is a complex process where cells must self-renew and differentiate at the right place and right time. Gene regulation during development involves sequences in the genome which affect the expression of genes locally, and transcription factors, proteins that bind these sequences and activate genes throughout the genome. At active regulatory sequences and genes, DNA is accessible to these proteins, while inactive DNA is tightly compacted.