Funded Projects

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).

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).

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.

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).

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.

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.

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. 

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.

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. 

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.

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.

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. 

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. 

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 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. 

Navigation through an environment to a remembered location is a critical skill we use every day. How does our brain accomplish such a task? Over the last few decades, several lines of evidence have suggested that a brain region called medial entorhinal cortex (MEC) supports navigation by encoding information our location and movement within an environment.

Many neurological diseases feature the death of neurons, but the mechanisms that mediate cell death in these disorders are unknown. Astrogliosis, the response of a cell-type called “astrocytes” to injury, is common to most diseases of the central nervous system (CNS), and recent studies in our lab suggest that some reactive astrocytes may release a protein that is potently toxic to neurons.

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.

Understanding the relationship between structure and function in the human brain is a key interest in neuroscience. In recent years the focus is turning to understanding the role of the white matter in human cognition, brain function and neurological disorders.

Electrodes implanted in the brain have great potential, with applications in neurodegenerative disease, brain-computer interfaces, and more. However, the presence of electrodes in brain tissue causes a response known as gliosis, in which a scar forms around the electrode, reducing its effectiveness and access to neurons.