A5022632094- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Growth Hormone and Insulin-like Growth Factors
- RNA regulation and disease
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Metabolism, Diabetes, and Cancer
- Circadian rhythm and melatonin
- Nuclear Receptors and Signaling
- Plant and animal studies
- Retinal Development and Disorders
- Aging and Gerontology Research
- Cancer, Hypoxia, and Metabolism
- Birth, Development, and Health
- Protein Degradation and Inhibitors
- Retinal Diseases and Treatments
- Lipid metabolism and disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mosquito-borne diseases and control
- NF-κB Signaling Pathways
- Skin and Cellular Biology Research
- Medicinal Plant Pharmacodynamics Research
- Heat shock proteins research
- FOXO transcription factor regulation
Synthego (United States)
2018-2024
University of Michigan
2002-2022
Stanford University
2010-2022
Menlo School
2020
BioMarin (United States)
2016-2017
Efficient and precise genome editing requires a fast, quantitative, inexpensive assay to assess genotype following editing. Here, we present ICE (Inference of CRISPR Edits), which enables robust analysis edits using Sanger data. proposes potential outcomes for with guide RNAs, then determines are supported by the data via regression. The algorithm is reproducible, it can be used analyze experiments within days after transfection. We also confirm that produces accurate estimates across...
Abstract Efficient precision genome editing requires a quick, quantitative, and inexpensive assay of outcomes. Here we present ICE (Inference C RISPR E dits), which enables robust analysis CRISPR edits using Sanger data. proposes potential outcomes for with guide RNAs (gRNAs) then determines are supported by the data via regression. Additionally, develop score called ICE-D (Discordance) that can provide information on large or unexpected edits. We empirically confirm through over 1,800...
Aging is accompanied by alterations in epigenetic marks that control chromatin states, including histone acetylation and methylation. Enzymes reversibly affect associated with active have recently been found to regulate aging Caenorhabditis elegans. However, relatively little known about the importance for of repressed chromatin. Here, we use a targeted RNAi screen C. elegans identify four demethylases significantly worm lifespan, UTX-1, RBR-2, LSD-1, T26A5.5. Interestingly, UTX-1 belongs...
Battle of the Sexes In many species, males compete with one another to propagate their own DNA, often detriment females (see Perspective by Promislow and Kaeberlein ). Shi Murphy (p. 536 , published online 19 December) discovered that mating in Caenorhabditis species causes mothers shrink die soon after they have ceased producing progeny. Males appear hijack longevity stress resistance pathways normally employed slow reproduction somatic aging times stress. Maures et al. 541 29 November)...
We have cloned and characterized cDNAs encoding the zebrafish IGF ligands receptors. Sequence comparison showed that primary structures of IGF-I, IGF-II, IGF-I receptors (IGF-IRs) been highly conserved in vertebrates. In contrast to presence a single IGF-IR gene mammals, two distinct genes, termed igf-1ra igf-1rb, were found zebrafish. Structural phylogenetic analyses indicated both genes are orthologous human igf-1r gene. Immunoprecipitation studies with specific antibodies expressed bind...
The biological activity and availability of IGFs are regulated by a group secreted proteins that belong to the IGF-binding protein (IGFBP) gene family. Although six IGFBPs have been identified studied in mammals, their nonmammalian orthologs remain poorly defined. In this study, we cloned characterized full-length zebrafish IGFBP-1. Sequence analysis indicated its structure is homologous mammalian Using situ RNA hybridization RT-PCR, discovered IGFBP-1 mRNA was present all early embryonic...
Abstract Following introduction of CRISPR-Cas9 components into a cell, genome editing occurs unabated until degradation its component nucleic acids and proteins by cellular processes. This uncontrolled reaction can lead to unintended consequences including off-target chromosomal translocations. To address this, we develop method for light-induced sgRNA termed CRISPRoff. Here show that inactivation ribonucleoprotein attenuates within cells allows titratable levels efficiency spatial...
Insulin-like growth factor binding protein (IGFBP)-5 is a conserved synthesized and secreted by vascular smooth muscle cells (VSMCs). IGFBP-5 binds to extracellular IGFs modulates IGF actions in regulating VSMC proliferation, migration, survival. also stimulates migration through an IGF-independent mechanism, but the molecular basis underlying this ligand-independent action unknown. In study, we show that endogenous or transiently expressed IGFBP-5-EGFP, not IGFBP-4-EGFP, localized nuclei of...
Abstract Interactions between the sexes negatively impact health in many species. In Caenorhabditis , males shorten lifespan of opposite sex—hermaphrodites or females. Here we use transcriptomic profiling and targeted screens to systematically uncover conserved genes involved male-induced demise C. elegans . Some (for example, delm-2 acbp-3 ), when knocked down, are specifically protective against demise. Others sri-40 extend with without males, suggesting general mechanisms protection....
Sexual interactions have a potent influence on health in several species, including mammals. Previous work C. elegans identified strategies used by males to accelerate the demise of opposite sex (hermaphrodites). But whether hermaphrodites evolved counter-strategies against remains unknown. Here we discover that young are remarkably resistant brief sexual encounters with males, whereas older succumb prematurely. Surprisingly, it is not their youthfulness protects hermaphrodites, but fact...
Previous work showed that the adapter protein SH2B 1beta (SH2B1) (SH2-B) binds to activated form of nerve growth factor (NGF) receptor TrkA and is critical for both NGF-dependent neurite outgrowth maintenance. To identify SH2B1beta-regulated genes outgrowth, we performed microarray analysis control PC12 cells stably overexpressing SH2B1beta (PC12-SH2B1beta) or dominant-negative SH2B1beta(R555E) [PC12-SH2B1beta(R555E)]. NGF-induced expression Plaur Mmp10 was greatly enhanced in PC12-SH2B1beta...
The adapter protein SH2B1 (SH2-B, PSM) is recruited to multiple ligand-activated receptor tyrosine kinases, including the receptors for nerve growth factor (NGF), insulin, and IGF-I as well cytokine receptor-associated Janus kinase family kinases. In this study, we examine SH2B1's function in NGF signaling. We show that depleting endogenous using short hairpin RNA against inhibits NGF-dependent neurite outgrowth, but not NGF-mediated phosphorylation of Akt or ERKs 1/2. has been hypothesized...
An intriguing question in cell biology is what targets proteins to, and regulates their translocation between, specific cellular locations. Here we report that the polybasic nuclear localization sequence (NLS) required for entry of adapter protein candidate human obesity gene product SH2B1β, also localizes SH2B1β to plasma membrane (PM), most probably via electrostatic interactions. Binding PM requires its dimerization domain. Phosphorylation serine residues near this region, potentially by...
The tyrosine kinase Janus 2 (JAK2) is activated by many cytokine receptors, including receptors for GH, leptin, and erythropoietin. However, very few proteins have been identified as binding partners JAK2. Using a yeast 2-hybrid screen, we steroid-sensitive gene-1 (SSG1)/coiled-coil domain-containing protein 80 (Ccdc80) JAK2-binding partner. We demonstrate that Ccdc80 preferentially binds activated, tyrosyl-phosphorylated JAK2 but not kinase-inactive (K882E) in both mammalian systems....
Abstract SARS-CoV-2 infection of human cells is initiated by the binding viral Spike protein to its cell-surface receptor ACE2. We conducted a targeted CRISPRi screen uncover druggable pathways controlling cells. found that BRD2 required for ACE2 transcription in lung epithelial and cardiomyocytes, inhibitors currently evaluated clinical trials potently block endogenous expression cells, including those nasal epithelia. Moreover, pharmacological inhibition with drug ABBV-744 inhibited...
The adapter protein SH2B1 is recruited to neurotrophin receptors, including TrkB (also known as NTRK2), the receptor for brain-derived neurotrophic factor (BDNF). Herein, we demonstrate that four alternatively spliced isoforms of (SH2B1α-SH2B1δ) are important determinants neuronal architecture and neurotrophin-induced gene expression. Primary hippocampal neurons from Sh2b1-/- [knockout (KO)] mice exhibit decreased neurite complexity length, BDNF-induced expression synapse-related immediate...
Efficient engineering of T cells to express exogenous tumor-targeting receptors such as chimeric antigen (CARs) or T-cell (TCRs) is a key requirement effective adoptive cell therapy for cancer. Genome editing technologies, CRISPR/Cas9, can further alter the functional characteristics therapeutic through knockout genes interest while knocking in synthetic that recognize cancer cells. Performing multiple rounds gene transfer with precise genome editing, termed multiplexing, remains challenge,...