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.

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.

The purpose of this collaborative project is to study neuronal mechanisms associated with social stress. In particular we will test whether the energy producing systems, known as mitochondria, in a specific set of brain cells are important to confer resilience to stressful stimuli. This research may lead to treatments of stress and anxiety disorders. 

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.

Stroke is the main cause of adult disability; 80% of survivors sustain motor (movement) deficits that interfere with activities of daily living. There exists no proven therapeutic strategy for motor recovery of the upper extremity following stroke.

Our ability to detect and interpret sounds relies on specialized sensory cells within the snail-shaped hearing organ of the inner ear—the cochlea. These hair cells sense physical movement and then convert that mechanical stimulus into a biological signal that we perceive as sound. These mechano-sensory cells perform this task within microseconds and can do so for sub-nanomechanical stimuli.

My proposed visit to the Van De Ville lab is centered on the idea to expand our methods beyond brain tumors to other neurological diseases using the Van De Ville lab’s expertise in neuro-imaging. Imaging genomics has been focused mainly on oncology; however, other neurological diseases can be studied in the same way.

Brain data analyses involves many steps and every step is prone to errors and uncertainties. Ignoring uncertainties can potentially leading to overconfident conclusions. To improve reproducibility it is important to propagate errors throughout the anlaysis.

Humans naturally learn to generate and process complicated sequential patterns. For example, a concert pianist can learn an enormous repertoire of memorized music. In neuroscience, it is widely thought that synaptic plasticity – the process by which the connections between neurons change response to experience – underlies such remarkable behavior.

A hallmark of the motor system is its ability to execute different skilled movements as the situation warrants, thanks to the flexibility of motor learning. Despite many behavioral studies on motor learning, the neural mechanisms of motor memory formation and modification remain unclear.

In the course of everyday functioning, animals (including humans) are constantly faced with real-world environments in which they are required to shift unpredictably between multiple, sometimes unfamiliar, tasks. But how brains support this rapid adaptation of decision making schema, and how they allocate resources towards learning novel tasks is largely unknown both neuroscientifically and algorithmically.

Human movement results from the coordination of muscles, tendons, joints, and other physiological elements.

Yi Lui's project aims to use deep brain microstimulation (DBMS), which causes even less brain damage and has higher spatial resolution than DBS, for memory recovery.