A5030835317- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- SARS-CoV-2 and COVID-19 Research
- Genomic variations and chromosomal abnormalities
- SARS-CoV-2 detection and testing
- Parasites and Host Interactions
- Health Systems, Economic Evaluations, Quality of Life
- Family and Patient Care in Intensive Care Units
- Infection Control and Ventilation
- Memory and Neural Mechanisms
- Neuroscience and Neuropharmacology Research
- 14-3-3 protein interactions
- Biosensors and Analytical Detection
- Intensive Care Unit Cognitive Disorders
- Geriatric Care and Nursing Homes
- Stress Responses and Cortisol
- Cardiac, Anesthesia and Surgical Outcomes
- Neurogenesis and neuroplasticity mechanisms
- Plant nutrient uptake and metabolism
- Amino Acid Enzymes and Metabolism
- COVID-19 epidemiological studies
- Polyamine Metabolism and Applications
The Francis Crick Institute
2018-2024
University College London
2020
National Hospital for Neurology and Neurosurgery
2020
University College London Hospitals NHS Foundation Trust
2020
Massachusetts Institute of Technology
2016-2018
Laureate Institute for Brain Research
2016
Stanford University
2016
University of Calgary
2016
Palo Alto University
2016
National Institute of Mental Health
2016
The basolateral amygdala (BLA) mediates associative learning for both fear and reward. Accumulating evidence supports the notion that different BLA projections distinctly alter motivated behavior, including to nucleus accumbens (NAc), medial aspect of central (CeM), ventral hippocampus (vHPC). Although there is consensus regarding existence distinct subsets neurons encoding positive or negative valence, controversy remains anatomical arrangement these populations. First, we map location more...
Loss-of-function mutations in CDKL5 kinase cause severe neurodevelopmental delay and early-onset seizures. Identification of substrates is key to understanding its function. Using chemical genetics, we found that phosphorylates three microtubule-associated proteins: MAP1S, EB2 ARHGEF2, determined the phosphorylation sites. Substrate phosphorylations are greatly reduced knockout mice, verifying these as physiological substrates. In mouse neurons, dendritic microtubules have longer...
Abstract CDKL5 is a brain-enriched serine/threonine kinase, associated with profound developmental and epileptic encephalopathy called deficiency disorder (CDD). To design targeted therapies for CDD, it essential to determine where expressed active in the brain test if compensatory mechanisms exist at cellular level. We generated conditional Cdkl5 knockout mice excitatory neurons, inhibitory neurons astrocytes. assess activity, we utilized phosphospecific antibody phosphorylated EB2,...
Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (
Despite mediating several essential processes in the brain, including during development, cyclin-dependent kinase-like 5 (CDKL5) remains a poorly characterized human protein kinase. Accordingly, its substrates, functions, and regulatory mechanisms have not been fully described. We realized that availability of potent selective small molecule probe targeting CDKL5 could enable illumination roles normal development as well diseases where it has become aberrant due to mutation. prepared analogs...
Despite mediating several essential processes in the brain, including during development, cyclin-dependent kinase-like 5 (CDKL5) remains a poorly characterized human protein kinase. Accordingly, its substrates, functions, and regulatory mechanisms have not been fully described. We realized that availability of potent selective small molecule probe targeting CDKL5 could enable illumination roles normal development as well diseases where it has become aberrant due to mutation. prepared analogs...
Abstract Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 ( CDKL5 ) cause deficiency disorder (CDD), a rare and severe neurodevelopmental associated with medically refractory early-life epilepsy, motor, cognitive, visual autonomic disturbances the absence of any structural brain pathology. Analysis genetic variants CDD have indicated that kinase function is central to disease encodes serine-threonine significant homology GSK3β, which has also been linked synaptic...