Browse wide-ranging research at the frontiers of neuroscience supported by Wu Tsai Neurosciences Institute grants, awards, and training fellowships.
Projects
A synthetic ultrasound neural interface for non-invasive and spatiotemporally precise chemogenetic and pharmacological neuromodulation
Controlling brain activity using chemicals and drugs is instrumental in neuroscience research, but current delivery methods for these compounds are imprecise. A proposed synthetic neural interface will allow for more controlled chemical and drug release by using ultrasound to precisely penetrate neural tissue.
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.
Assessing the feasibility of an autologous cell/gel therapy for spinal cord injury
This team has developed a new therapy for patients with spinal cord injury, involving injection into the spinal cord of patient-derived stem cells within an engineered protective gel. They will use their Neuroscience:Translate award to further test and develop this novel therapy in preparation for first-in-human clinical trials.
Assessing whether inhibitory rTMS improves brain pathology and language function in Self-limited Epilepsy with Centro-temporal Spikes (SeLECTS)
This team will use their Koret pilot grant award to study if language difficulties in children with epilepsy are caused by excessive connectivity in the brain. The team previously found that elevated connectivity is associated with poorer language, and that inhibitory transcranial magnetic stimulation (TMS) can reduce connectivity.
Assessment of MAP4K4 in regulating tumor cell invasion in a preclinical model of pediatric high-grade glioma
Pediatric high-grade gliomas (pHGGs) carry a poor prognosis with limited therapeutic options. This is in part due to the highly invasive behavior of malignant glioma cells, which infiltrate into normal brain parenchyma where they are inaccessible to surgical intervention and are poised to drive tumor recurrences.
Biomarkers of awareness and response to treatment in obsessive-compulsive disorder (BARTOC): Implementing EEG-based biomarkers of cognitive control in a pilot study of nitrous oxide inhalation vs placebo in OCD
This project is focused on developing EEG-based measures of cognitive control and conflict processing in patients with obsessive-compulsive disorder (OCD). OCD is characterized by recurrent, intrusive, and distressing thoughts, and patients are often limited by rigid, inflexible behavioral routines as well as poor clinical insight into their illness.
Brain response to influenza virus infection in the lung
The immune system is subjected to neuroendocrine regulation and control by the brain. One such example is the induction of glucocorticoid (GC) in infectious diseases. GC is synthesized and released by the adrenal glands via the hypothalamic-pituitary-adrenal gland (HPA) axis which is initiated from the hypothalamic paraventricular nucleus (PVN).
Clinical translation of a new PET radiotracer for mapping innate immune activation in multiple sclerosis and other neurodegenerative diseases
This team recently identified a selective biomarker of inflammation-promoting immune cells in the central nervous system. They will use their Neuroscience:Translate award to develop non-invasive molecular imaging strategies to distinguish between harmful (pro-inflammatory) and helpful (anti-inflammatory) immune cells in patients with Multiple sclerosis (MS).
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.
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.
Creating a pharmacologic stroke recovery therapy
This team has identified a promising protein-based therapeutic to improve stroke recovery. The team will use the Neuroscience:Translate award to identify key components of this protein to maximize its therapeutic potential for stroke treatments.
Decoding stem cell-induced recovery in time and space: a longitudinal DTI and MRS study to assess microstructural and metabolic changes following stem cell transplantation in stroke-injured rat brains
Intraparenchymal transplantation of human neural stem cells (hNSCs) shows therapeutic potential for patients with chronic ischemic stroke. However, the underlying mechanisms of how hNSCs drive recovery remain elusive.
Defining the temporal and spatial CSF secretome by TurboID labeling
The cerebrospinal fluid (CSF) influences the development, maturation, and aging of the nervous system in ways that are not fully understood. TurboID, a synthetically engineered enzyme, can label CSF proteins to track their sources and development, providing insight into the roles the CSF plays in development, health, and disease.
EEG markers of self-efficacy and self-regulation in chronic pain patients with and without heavy drinking
This project aims to identify brain-based EEG markers of self-efficacy and self-regulation, which are the two critical treatment targets for people with chronic pain and comorbid heavy alcohol use. Such objective markers will assist in accurate diagnosis and assessment of treatment responses, which may enable a precision medicine approach for chronic pain and substance use disorders.
Engineering objective physiologic measures to characterize nonmotor aspects of Parkinson’s disease
Parkinson’s disease (PD) is a complex, heterogeneous neurodegenerative disorder whose prevalence is increasing rapidly. Not only do patients experience motor symptoms, but many experience debilitating nonmotor symptoms caused by peripheral degeneration in the autonomic nervous system, including atrophy of the vagus nerve, and the enteric nervous system.
Evaluating the immunomodulatory role of circular RNAs in microglia
First-in-class RNA sensors for studying myelin dynamics and disease
RNA sensors are a cutting edge tool in synthetic biology for probing complex molecular pathways and creating “smart” molecular circuits in cells. This team leverages state-of-the-art synthetic biology tools to understand how oligodendrocytes contribute to Alzheimer’s disease and other demyelinating disorders.
Genetically-encoded voltage integrators for stable tagging of activated or inhibited neural ensembles in vivo
A major goal in systems neuroscience is to discover how patterns of activity in neural circuits produce and regulate behavior. Using synthetic biology tools, this team aims to develop first-in-class genetically encoded voltage integrators (GEVIns) capable of sensing and responding to both activation and inhibition of neurons.
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.
High-resolution profiling of Alzheimer’s brain resilience
How do early life experiences shape the neural underpinnings of caregiver olfactory recognition?
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.
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.
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.
Interpretable machine learning to decipher gene regulation in brain development and disruption in disease
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.