A5010372322- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Protein Structure and Dynamics
- Cholesterol and Lipid Metabolism
- Genomics and Chromatin Dynamics
- Microbial Natural Products and Biosynthesis
- Enzyme Structure and Function
- Single-cell and spatial transcriptomics
- Cellular Mechanics and Interactions
- Pluripotent Stem Cells Research
- Antimicrobial Peptides and Activities
- Bacterial biofilms and quorum sensing
- Muscle Physiology and Disorders
- Genetics and Neurodevelopmental Disorders
- Antimicrobial Resistance in Staphylococcus
- Protein Tyrosine Phosphatases
- Synthetic Organic Chemistry Methods
- 14-3-3 protein interactions
- Immune cells in cancer
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Developmental Biology and Gene Regulation
- Telomeres, Telomerase, and Senescence
- Down syndrome and intellectual disability research
University of California, San Diego
2013-2024
Massachusetts Institute of Technology
2019-2023
University of Colorado Denver
2014
Persistent DNA double-strand breaks (DSBs) in neurons are an early pathological hallmark of neurodegenerative diseases including Alzheimer's disease (AD), with the potential to disrupt genome integrity. We used single-nucleus RNA-seq human postmortem prefrontal cortex samples and found that excitatory AD were enriched for somatic mosaic gene fusions. Gene fusions particularly damage repair senescence signatures. In addition, structural variations burdened DSBs CK-p25 mouse model...
Eukaryotic protein kinases (EPKs) regulate numerous signaling processes by phosphorylating targeted substrates through the highly conserved catalytic domain. Our previous computational studies proposed a model stating that properly assembled nonlinear motif termed Regulatory (R) spine is essential for activity of EPKs. Here we define required intramolecular interactions and biochemical properties R-spine newly identified "Shell" surrounds using site-directed mutagenesis various in vitro...
A new model of kinase regulation based on the assembly hydrophobic spines has been proposed. Changes in their positions can explain mechanism activation. Here, we examined mutations human cancer for clues about by focusing initially to Phe. We identified a selected number Phe small group kinases that included BRAF, ABL1, and epidermal growth factor receptor. Testing some these found one impaired ATP binding catalytic activity but promoted noncatalytic allosteric functions. Other functioned...
Down syndrome (DS) is a genetic disorder driven by the triplication of chromosome 21 (T21) and characterized wide range neurodevelopmental physical disabilities. Transcriptomic analysis tissue samples from individuals with DS has revealed that T21 induces genome-wide transcriptional disruption. However, consequences on nuclear architecture its interplay transcriptome remain unknown. In this study, we find unlike human induced pluripotent stem cells (iPSCs), iPSC-derived neural progenitor...
Eukaryotic protein kinases regulate most cellular functions by phosphorylating targeted substrates through a highly conserved catalytic core. In the active state, core oscillates between open, intermediate, and closed conformations. Currently, intramolecular interactions that state mechanics are not well understood. Here, using cAMP-dependent kinase as representative model coupled with biochemical, biophysical, computational techniques, we define set of electrostatic hydrophobic working...
BlaI is a repressor of BlaZ, the beta-lactamase responsible for penicillin resistance in Staphylococcus aureus. Through screening transposon library S. aureus Newman susceptibility to cathelicidin antimicrobial peptide, we discovered as novel factor. Additionally, through integrational mutagenesis and MRSA Sanger 252 strains, confirmed role human murine cathelidicin showed that it contributes virulence whole blood infection models. We further demonstrated could be target innate immune-based...
Marine sponges harbour abundant and diverse bacterial communities, providing an ideal environment for cell-density-dependent cell–cell signalling, termed quorum sensing. The marine sponge symbiont Ruegeria sp. KLH11 produces mainly long chain acylhomoserine lactones (AHLs) has been developed as a sensing model roseobacterial symbionts. Two pairs of luxR/I homologues were identified by genetic screening designated ssaRI ssbRI (sponge-associated locus A or B, luxR/luxI homologue). In this...
Neural circuits governing all motor behaviors in vertebrates rely on the proper development of neurons and their precise targeting limb muscles. Transcription factors are essential for neuron development, regulating specification, migration, axonal targeting. While transcriptional regulation early stages specification is well-established, much less known about role transcription later maturation terminal arborization. Defining molecular mechanisms these critical elucidating how constructed....
Summary Apolipoprotein E4 (APOE4) is the greatest known genetic risk factor for developing late- onset Alzheimer’s disease and its expression in microglia associated with pro- inflammatory states. How interaction of APOE4 neurons differs from expressing disease-neutral allele APOE3 currently unknown. Here, we employ CRISPR-edited induced pluripotent stem cells (iPSCs) to dissect impact neuron-microglia communication. Our results reveal that induces a distinct metabolic program marked by...