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.
High-speed force probes for deconstructing the biophysics of mechanotransduction
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.
High-speed nanomechanical probing of auditory mechano-sensitive cells
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.
Quantitative imaging for multi-scale modeling of neurological diseases
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.
Improve reproducibility and transparency in the field of neuroimaging by applying nonparametricstatistical methods and writing R packages.
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.
Biologically plausible neural algorithms for learning structured sequences
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.
Answering research questions in neural control through crowdsourced challenges
Human movement results from the coordination of muscles, tendons, joints, and other physiological elements.
Novel haptic interfaces for studying human perception in virtual environments
Modelling the Pupil Light Reflex for Non-Image Forming Vision
Although you’re aware of the light that you see, light also affects us in ways that you might not appreciate. These so called “non-image forming” (NIF) pathways were recently discovered, they start in the human eye before projecting to over a dozen brain regions. They modulate aspects of human function including our daily rhythms, our sleep patterns, the way we feel and the way we think.
Controlling schistosomiasis via CRISPR/CAS9-mediated gene drive
Schistosomiasis is a parasitic disease second only to malaria in its human health and economic impact on tropical nations.