A5050005867- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- Neurobiology and Insect Physiology Research
- Circadian rhythm and melatonin
- Plant Molecular Biology Research
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Cholinesterase and Neurodegenerative Diseases
- Lipid metabolism and biosynthesis
- Tissue Engineering and Regenerative Medicine
- Congenital Diaphragmatic Hernia Studies
- Neonatal Respiratory Health Research
- CAR-T cell therapy research
- Retinal Development and Disorders
- Nuclear Structure and Function
- Chromosomal and Genetic Variations
- Endoplasmic Reticulum Stress and Disease
- Sleep and Wakefulness Research
- melanin and skin pigmentation
- Integrated Circuits and Semiconductor Failure Analysis
University of Pennsylvania
2015-2024
Cardiovascular Institute of the South
2020-2024
University of Illinois Chicago
2023-2024
Children's Hospital of Philadelphia
2015
During the stepwise specification and differentiation of tissue-specific multipotent progenitors, lineage-specific transcriptional networks are activated or repressed to orchestrate cell specification. The gas-exchange niche in lung contains two major epithelial types, alveolar type 1 (AT1) AT2 cells, timing lineage these cells is critical for correct formation this postnatal survival. Integrating cell-specific tracing studies, spatially specific mRNA transcript protein expression,...
Background: Gene regulatory networks control tissue homeostasis and disease progression in a cell type–specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how specificity of their function is achieved are poorly understood. BRD4 (bromodomain-containing protein 4), member BET (bromo- extraterminal domain) family ubiquitously acetyl-lysine reader proteins, plays pivotal role as coactivator enhancer signaling across diverse types...
Across species, sleep in young animals is critical for normal brain maturation. The molecular determinants of early life remain unknown. Through an RNAi-based screen, we identified a gene, pdm3, required maturation Drosophila. Pdm3, transcription factor, coordinates developmental program that prepares the to later execute high levels juvenile adult sleep. PDM3 controls wiring wake-promoting dopaminergic (DA) neurites sleep-promoting region, and loss prematurely increases DA inhibition...
Autophagy is a major catabolic degradation and recycling process that maintains homeostasis in cells especially important postmitotic neurons. We implemented high-content phenotypic assay to discover small molecules promote autophagic flux completed target identification validation studies identify protein targets modulate the autophagy pathway neuronal health survival. Efficient syntheses of prioritized compounds were developed readily access analogues initial hits, enabling...
Abstract In diseased organs, stress-activated signaling cascades alter chromatin, triggering broad shifts in transcription and cell state that exacerbate pathology. Fibroblast activation is a common stress response worsens lung, liver, kidney heart disease, yet its mechanistic basis remains poorly understood 1,2 . Pharmacologic inhibition of the BET family transcriptional coactivators alleviates cardiac dysfunction associated fibrosis, providing tool to mechanistically interrogate...
Abstract Abnormal increase in axonal lysosome abundance is associated with multiple neurodegenerative diseases including Alzheimer’s disease. However, the underlying mechanisms and disease relevance are not fully understood. We have recently identified RH1115 as a small molecule modulator of autophagy-lysosomal pathway that regulates positioning neurons. This allowed us to manipulate neuronal distribution axons interrogate its contribution both optimal functioning pathology. demonstrate only...
Abstract Gene regulatory networks control tissue plasticity during basal homeostasis and disease in a cell-type specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how tissue-specificity of their function is achieved are poorly understood. BRD4, member BET (Bromo- Extra-Terminal domain) family ubiquitously acetyl-lysine reader proteins, plays pivotal role as coactivator enhancer signaling across diverse types both health disease,...
Abstract Our ability to identify the particular transcription factors that maintain cell type is limited. Identification of by their type-specific expression or participation in developmental regulation has been only modestly successful. We hypothesized because often resilient perturbations, transcriptional response perturbations would identity-maintaining factors. developed Perturbation Panel Profiling (P 3 ) as a framework for perturbing cells dozens conditions and measuring gene...
Summary Across species, sleep in young animals is critical for normal brain maturation. In contrast to mature adult sleep, the molecular determinants of early life remain unknown. Through an RNAi-based screen, we identified a gene, pdm3 , required maturation Drosophila . Pdm3 transcription factor, acts during nervous system development coordinate ingrowth wake-promoting dopaminergic neurites sleep-promoting region. Loss PDM3 prematurely increases inhibition center, abolishing juvenile state....