A5075448735- Pancreatic function and diabetes
- RNA modifications and cancer
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Diabetes and associated disorders
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Diabetes Management and Research
- Cell Image Analysis Techniques
- Ubiquitin and proteasome pathways
- ATP Synthase and ATPases Research
- Genomic variations and chromosomal abnormalities
- RNA and protein synthesis mechanisms
- Phagocytosis and Immune Regulation
- FOXO transcription factor regulation
- Advanced Fluorescence Microscopy Techniques
- Spectroscopy Techniques in Biomedical and Chemical Research
- Plant Molecular Biology Research
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
Rockefeller University
2024
Columbia University Irving Medical Center
2018-2021
Columbia University
2011-2019
Tel Aviv University
2007
Many pancreatic transcription factors that are essential for islet cell differentiation have been well characterized; however, because they often expressed in several different populations, their functional hierarchy remains unclear. To parse out the spatiotemporal regulation of differentiation, we used a Neurog3-Cre allele to ablate Nkx2.2, one earliest and most broadly factors, specifically Neurog3+ endocrine progenitor lineage (Nkx2.2△endo). Remarkably, many components β transcriptional...
Regulation of cell differentiation programs requires complex interactions between transcriptional and epigenetic networks. Elucidating the principal molecular events responsible for establishment maintenance fate identities will provide important insights into how lineages are specified maintained improve our ability to recapitulate in vitro. In this study, we demonstrate that Nkx2.2 is part a large repression pancreatic β cells includes DNMT3a, Grg3, HDAC1. Mutation endogenous tinman (TN)...
Inactivation of the β-cell transcription factor NEUROD1 causes diabetes in mice and humans. In this study, we uncovered novel functions during murine islet cell development differentiation human embryonic stem cells (HESCs) into insulin-producing cells. mice, determined that Neurod1 is required for perinatal proliferation α- β-cells. Surprisingly, apoptosis only makes a minor contribution to loss when deleted. HESCs severely impaired their from pancreatic progenitors insulin-expressing...
The homeodomain transcription factor Nkx2.2 is essential for pancreatic development and islet cell type differentiation. We have identified Tm4sf4, an L6 domain tetraspanin family member, as a transcriptional target of that greatly upregulated during pancreas in Nkx2.2–/– mice. Tetraspanins proteins recruit other membrane receptors to form active signaling centers coordinate processes such adhesion, migration In this study, we determined Tm4sf4 localized the ductal epithelial compartment...
Summary The roles of individual eukaryotic translation initiation factor 3 (eIF3) subunits are largely unclear, although some essential, while others thought to have regulatory roles. ‘e’ subunit, also known as Int‐6/Int6, is a candidate for subunit it not essential in yeasts. eIF3e associates with the COP9 signalosome, and localizes nucleus certain tissues. To further elucidate eIF3e, we taken genetic approach using Arabidopsis model system. Overexpression results defects similar mutations...
Danforth's short tail mutant (Sd) mouse, first described in 1930, is a classic spontaneous exhibiting defects of the axial skeleton, hindgut, and urogenital system. We used meiotic mapping 1,497 segregants to localize mutation 42.8-kb intergenic segment on chromosome 2. Resequencing this region identified an 8.5-kb early retrotransposon (ETn) insertion within highly conserved regulatory sequences upstream Pancreas Specific Transcription Factor, 1a (Ptf1a). This resulted up tenfold increased...
The COP9 signalosome protein complex has a central role in the regulation of development multicellular organisms. While function this ubiquitin-mediated degradation is well established, results over past few years have hinted that may more broadly gene expression. Here, using DamID technology, we show subunit 7 functionally associates with large number genomic loci Drosophila genome, and expression many genes within these signalosome-dependent. This association likely direct as CSN7 binds...
Groucho-related genes (GRGs) are transcriptional co-repressors that crucial for many developmental processes. Several essential pancreatic transcription factors capable of interacting with GRGs; however, the in vivo role GRG-mediated repression pancreas development is still not well understood. In this study, we used complex mouse genetics and transcriptomic analyses to determine GRG3 β cell development, absence Grg3 there compensatory upregulation Grg4Grg3/4 double mutant mice have severe...
Neuronal diversity and function are intricately linked to the dynamic regulation of RNA metabolism, including splicing, localization, translation. Electrophysiologic studies synaptic plasticity, models for learning memory, disrupted in Fragile X Syndrome (FXS). FXS is characterized by loss FMRP, an RNA-binding protein (RBP) known bind suppress translation specific neuronal RNAs. Since molecular have demonstrated that plasticity CA1 excitatory hippocampal neurons protein-synthesis dependent,...
The neuronal RNA-binding protein (RBP) family nELAVL regulates key processes by binding directly to target RNA transcripts. In this study, we demonstrate that ELAVL3 is the predominant paralog expressed in D1 and D2 medium spiny neurons of striatum. To investigate its function, developed cTag-crosslinking immunoprecipitation (CLIP) generate RBP-RNA interaction maps from these neurons. By integrating data ELAVL3-cTag Elavl3 knockout mice, identified distinct regulatory effects on alternative...