Browse wide-ranging research at the frontiers of neuroscience supported by Wu Tsai Neurosciences Institute grants, awards, and training fellowships.
Projects
Investigating severe traumatic brain injury using a novel human CSF cell-free mRNA gene panel
This team aims to be the first to study the cellular and molecular impact of traumatic brain injury by studying genetic material in human cerebrospinal fluid. This will help clinicians and researchers ID markers of brain resilience after injury, and ultimately improve treatment for severe TBI.
AI to model and boost brain repair and resilience during aging
This team aims to use the power of artificial intelligence to make new findings about brain aging, with the goal of boosting brain repair and resilience. They are particularly interested in spatial changes in the brain during aging. Their goal is to understand how aging renders the brain susceptible to injuries that accentuate neurodegenerative diseases.
Convergence of signals for pruning at a synaptic receptor implicated in Alzheimer's disease
Memories are stored at synapses and circuits, which tragically are pruned and deconstructed in Alzheimer's disease (AD). Genetic mutations including APP generate high levels of soluble oligomeric beta amyloid (oAbeta42), leading to insoluble beta amyloid plaques - hallmarks of late-stage disease. Clinical trials have designed "plaque-busting" drugs assuming that plaques cause disease.
Unconventional IRE1 activation for promoting brain resilience
It has been appreciated for decades years 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 more or less resilient are not fully understood.
Myelin – an untapped target for preventing or reversing brain aging
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.
Clinically translating ultrasonic CSF clearing to enhance brain resilience
Recent data suggest that increased circulation of cerebrospinal fluid (CSF) to clear the brain and spinal cord of waste is associated with improved outcomes in aging and recovery from brain injury, suggesting that inducing CSF clearing could enhance brain resilience. However, a therapeutic modality for directly inducing CSF clearing has not been available.
Towards rescuing diverse forms of proteinopathies by induction of autophagic flux
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.
Identifying the intrinsic biological factors of APOE risk and resilience across relevant iPSC-derived brain cell types
Brain resilience, the ability to withstand adverse outcomes despite significant risk factors, is crucial in late-onset Alzheimer’s disease (AD), where the Apolipoprotein E4 (APOE4) gene is a major risk factor. Carrying APOE4 increases AD risk up to 15-fold compared to the ApoE3 allele.
Harnessing ketone metabolites for brain health and brain resilience
The ketogenic diet, fasting, and ketone supplements switch the body's fuel source from carbs to fats, a state known as ketosis. This switch can be good for your brain, helping to keep it healthy and resilient to damage. In ketosis, your liver makes a special fat-derived fuel called beta-hydroxybutyrate, or BHB for short.
The role of microglia in brain resilience to pathological protein aggregates
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.
Identifying mechanisms of dopaminergic neuron resilience and their roles in Parkinson’s disease
Parkinson’s disease (PD) is the second most common neurodegenerative disease, characterized by progressive motor deficits such as tremor, muscle stiffness, and slowness of movement, and affects 6 million worldwide. Despite ongoing efforts to discover the mechanisms underlying this disease, PD remains an incurable disorder.
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.