Funded Projects

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.

Myelin, traditionally thought of as the brain's electrical insulator, has emerged as an active and dynamic regulator of brain functions including neuroprotection, learning, and memory. Myelin dysfunction and loss is increasingly found to be central to brain aging and neurodegenerative diseases including Alzheimer's.

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 individuals manage to maintain memory function, which raises important questions about the brain mechanisms that underly memory resilience.

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.

The intricate workings of signaling pathways are well-established with regard to neurodevelopment. Yet, the implications of these pathways for sustaining brain health and resilience during the aging process are not clear.

This team is working on understanding which patients with mild cognitive impairment (MCI) will best benefit from cognitive training. They are researching a multimodal approach to understand this question and will use their Koret pilot grant award to evaluate high-density EEG biomarkers for successful cognitive training in MCI. 

This project's goal is to enhance brain resilience by promoting vascular brain health during aging. The research team's overarching hypothesis is that many people experience cognitive decline and dementia due to pathological aging.

This team is developing new transcranial magnetic stimulation methods that optimize neuromodulation effects using music-induced brain state dynamics.

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.

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.

Fang Wang has been developing novel steady-state EEG techniques to reveal the underlying neural dynamics involved in the acquisition of reading skills in children. She will use the Koret award to extend her findings in typically developing children to children with dyslexia, illustrating how cortical challenges in the temporal dynamics of visual processing can contribute to dyslexia.

More and more studies suggest that infections may be an important cause of dementia and possibly brain aging more generally. The most convincing evidence exists for herpesviruses, which “hibernate” in the nervous system. Recently,  an innovative causal approach in data from the United Kingdom has been used to suggest that shingles (herpes zoster) vaccination prevents or delays dementia.

Normal aging and neurodegenerative disease are typically characterized by accumulation of waste products inside the brain and in particular by aggregation of various types of proteins like Amyloid-beta outside of cells or the proteins Tau, alpha-synuclein, and TDP-43 inside cells.

Current treatments for neurodegenerative disorders (proteinopathies) offer limited efficacy and typically target specific genetic forms. The goal of this research project is to discover targets shared across proteinopathies and advance the development of early diagnostic/prognostic tools and disease-modifying pan-proteinopathy approaches.

Psychedelics profoundly alter human consciousness through activation of 5-HT2A receptor proteins in the brain. This team aims to develop a molecular probe to permanently illuminate 5-HT2A receptors without modifying their function or expression, allowing scientists to better study the effects of psychedelics on these receptors.

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. 

It has been appreciated for decades that cognitive decline and dementia are frequently accompanied by changes that cause proteins within brain cells to clump abnormally into structures called neurofibrillary tangles. Resilient brains are better able to resist this process but the underlying mechanisms for why individuals’ brains are either more or less resilient are not fully understood.

The medial entorhinal cortex (MEC), the brain’s “inner GPS”, contains an internal map of external space. Rather than representing a static spatial map, however, MEC neurons can spontaneously switch between multiple maps (Low et al., 2021). In this project, we will investigate if spontaneous map switches reflect changes in an animal’s latent internal state.

Constipation and diarrhea, caused by aberrant water absorption in the colon, impose substantial health burdens. The enteric nervous system (ENS) harbors a specialized circuit for water absorption, the secretomotor/vasodilator circuit, but its role in the proximal colon remains poorly understood.

Understanding representational drift—the brain’s evolving representation of its environment—is pivotal to gaining insights into neural computation. Despite its significance, the study of representational drift has been constrained by the scarcity of suitable datasets and methods.

This team aims to understand differences in language processing between bilingual and monolingual speakers and how these differences contribute to neuroplasticity. Their Koret project will use EEG to discover how semantic predictions are formed and whether knowledge of multiple languages influences these predictions.

In this highly interdisciplinary project, PhD candidate Alberto Tono is pursuing the novel application of combined EEG and immersive reality to streamline workflows in building design and construction.

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.