Browse wide-ranging research at the frontiers of neuroscience supported by Wu Tsai Neurosciences Institute grants, awards, and training fellowships.
Projects
Rejuvenating sleep to enhance brain resilience with age
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).
Elucidating the role of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
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).
Neuron-glia interactions in regulating protein aggregation in human cell models.
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.
The origin of neurodegeneration: insight from a unique colonial chordate
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).
Determining the role of circadian transcriptional control in myelin-forming precursors in neurodegeneration
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.
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.
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.
A principled investigation into the heterogeneous coding properties of medial entorhinal cortex that support accurate spatial navigation
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.
Understanding why neurons die in disease
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.
Geometric analysis and variability mapping in human white matter brain structures
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.
Understanding cellular responses induced by chronic implantation of electrodes using a novel human neural differentiation platform
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.
Modeling proprioceptive deficits for the design of novel sensory augmentation for post-stroke movement rehabilitation
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.
Neural mechanisms of learning multiple motor skills and implications for motor rehabilitation
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.
Engineering versatile deep neural networks that model cortical flexibility
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.
Deep brain microstimulation for memory recovery
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.
Determining higher-order organization of control and epileptic brain networks at single cell resolution
Dr. Darian Hadjiabadi aims to identify higher-order features of neuronal circuits responsible for seizure initiation and propagation by quantifying mesoscale-network reorganization in genetic models of zebra sh that faithfully recapitulate seizure dynamics in humans.
Synaptic rules and circuit architectures for learning from feedback
Dr. Brandon Jay Bhasin will use engineering principles from modern control theory, experimental neuroscience and computational neuroscience to significantly advance understanding of how feedback driven plasticity in a tractable neural circuit is orchestrated across multiple synaptic sites and over various timescales so that circuit dynamics are changed to improve performance.
Weak supervision in medical multi-modal time series
The project aims to alleviate this bottleneck by developing a weak supervision system that optimally deals with time-series data and takes advantage of multiple data modalities.
A spatiotemporally-resolved circuit model of the physiologic and behavioral effects of subanesthetic ketamine activity in the limbic system
Developing a platform of biocompatible nanoparticles that uncage a drug payload upon ultrasound application.
A multi-rank statistical model to determine the impact of behavioral state on navigational coding by medial entorhinal cortex
Behavioral state—such as alertness or exhaustion—dramatically impacts how our brains function. Yet, in spite of the key role that it plays in cognition, how behavioral state influences brain function remains a central mystery in neuroscience.
How do Schwann cells sort and myelinate axons in the developing peripheral nervous system?
Schwann cells (SCs) sort and myelinate peripheral axons, and impairments in either process can cause long-term disability. There are no therapeutic strategies for targeting SC dysfunction, underscoring the need to investigate mechanisms of sorting and myelination. Both processes require highly motile SC cytoplasmic protrusions, but the basis of this motility is unclear.