Funded Projects

We understand a lot about how the brain gets rewired when learning a new skill by repetitive practice, such as hitting a curveball. However, how learning and experience alter the innate behaviors that we are born with is poorly understood.

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).

Millions of people are blind, yet we still don’t have the technology to satisfactorily restore vision. I aim to create a prosthetic device to do so. This device can be implanted in the eyes of a blind patient, resting on a tissue layer called the retina.

Brain-computer interfaces (BCIs) are systems that enable using neural activity to control and interact with external devices. For people who lose the ability to move or speak due to injury or disease, BCIs provide a potential avenue to restore this loss of function.

It is more common nowadays for people to have their own wearable devices to measure physiological signals like heart rate and respiration to keep track of physical diseases. However, monitoring decline in cognitive functions or development of neurodegenerative diseases, such as Parkinson’s (PD), is still complex and tricky.

While acute pain is an important biological signal in response to injured tissue, chronic pain occurs when the pain signaling outlasts the initial injury and has deleterious effects on health and quality of life. Chronic pain represents an enormous public health burden with few therapeutic options.

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.

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.

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.

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. 

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.

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.

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.

One in three people will develop Alzheimer’s disease or another dementia during their lifetime, but effective treatment still does not exist despite intense efforts. Recently, blood from young mice has been found to rejuvenate several tissues of old mice, including the brain.

Precise neural circuit assembly is critical for appropriate function of the nervous system. A functional circuit requires proper targeting and matching of axons and dendrites of pre- and post-synaptic neurons. However, our understanding of the mechanisms that establish wiring specificity of complex neural circuit is far from complete.

    More than 60 million people in the United States currently suffer from a serious mental illness, and the associated financial, productivity and human suffering costs are only projected to rise in the near future.

Cyclic adenosine monophosphate (cAMP) is an important intracellular messenger that plays a critical role in the development of the central and peripheral nervous system. However, the mechanisms of action of cAMP in the nervous system development are poorly understood and there are currently no suitable methods to visualize cAMP in the cells of living animals.