A5036068634- RNA modifications and cancer
- Hedgehog Signaling Pathway Studies
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- HVDC Systems and Fault Protection
- Kruppel-like factors research
- Chemical Reactions and Isotopes
- Amino Acid Enzymes and Metabolism
- Receptor Mechanisms and Signaling
- Photosynthetic Processes and Mechanisms
- Diatoms and Algae Research
- Chromatin Remodeling and Cancer
- Click Chemistry and Applications
- Galectins and Cancer Biology
- Algal biology and biofuel production
- Advanced Polymer Synthesis and Characterization
- Microfluidic and Bio-sensing Technologies
- Cholesterol and Lipid Metabolism
- Science, Research, and Medicine
- Cardiac tumors and thrombi
Yale University
2021-2024
Stanford University
2012-2022
University of Chicago
2008-2022
Howard Hughes Medical Institute
2016-2020
Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol not just but also sufficient to activate signaling by Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. influences Hh directly activating Smoothened (SMO), an orphan GPCR transmits signal across membrane all animals. Unlike GPCRs, which are regulated through their heptahelical transmembrane domains, SMO activated its extracellular cysteine-rich...
The Hedgehog (Hh) signal is transduced across the membrane by heptahelical protein Smoothened (Smo), a developmental regulator, oncoprotein and drug target in oncology. We present 2.3 Å crystal structure of extracellular cysteine rich domain (CRD) vertebrate Smo show that it binds to oxysterols, endogenous lipids activate Hh signaling. oxysterol-binding groove CRD analogous used Frizzled 8 bind palmitoleyl group Wnt ligands similar pockets other Frizzled-like CRDs hydrophobic ligands....
Ribosomal RNAs (rRNAs) have long been known to carry chemical modifications, including 2'O-methylation, pseudouridylation, N6-methyladenosine (m6A), and N6,6-dimethyladenosine. While the functions of many these modifications are unclear, some highly conserved occur in regions ribosome critical for mRNA decoding. Both 28S rRNA 18S single m6A sites, while methyltransferase ZCCHC4 has identified as enzyme responsible modification, modification remained unclear. Here, we show that METTL5-TRMT112...
Smoothened (SMO) transduces the Hedgehog (Hh) signal across plasma membrane in response to accessible cholesterol. Cholesterol binds SMO at two sites: one extracellular cysteine-rich domain (CRD) and a second transmembrane (TMD). How these sterol-binding sites mediate activation ligand Sonic (SHH) remains unknown. We find that mutations CRD (but not TMD) reduce fold increase activity triggered by SHH. SHH also promotes photocrosslinking of sterol analog intact cells. In contrast, binding TMD...
Dihydrouridine is a modified nucleotide universally present in tRNAs, but the complete dihydrouridine landscape unknown any organism. We introduce sequencing (D-seq) for transcriptome-wide mapping of D with single-nucleotide resolution and use it to uncover novel classes dihydrouridine-containing RNA yeast which include mRNA small nucleolar (snoRNA). The sites are concentrated conserved stem-loop regions consistent role folding many functional structures. demonstrate synthase (DUS)-dependent...
Abstract Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function this mark ESCs differentiating embryoid bodies. Transcriptome-wide mapping reveals hundreds messenger RNAs marked by 5hmC at sites characterized defined unique consensus sequence particular features....
ABSTRACT Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. oxysterols naturally occurring molecules that were shown osteogenic differentiation vitro fusion vivo. The purpose of this study was identify an oxysterol more suitable for clinical development than those previously reported, evaluate its ability osteogenesis rats Among 100 analogues synthesized, Oxy133 induced significant expression markers Runx2, osterix...
We studied the self-assembly of inorganic nanocrystals (NCs) confined inside nanoliter droplets (plugs) into long-range ordered superlattices. showed that a capillary microfluidic platform can be used for optimization growth conditions NC superlattices and provide insights kinetics assembly process. The utility our approach was demonstrated by growing large (up to 200 μm) three-dimensional (3D) various NCs, including Au, PbS, CdSe, CoFe2O4. also it is possible grow 3D binary nanoparticle in plugs.
The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of evolutionarily conserved Hedgehog (Hh) pathway. Although aspects Smo signaling are from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and ability vertebrate induce distinct protein-dependent independent signals response ligand. Whereas canonical Gli transcriptional effectors occurs a protein-independent manner,...