A5100610135- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Spine and Intervertebral Disc Pathology
- Lipid Membrane Structure and Behavior
- Alzheimer's disease research and treatments
- Musculoskeletal pain and rehabilitation
- Photoreceptor and optogenetics research
- Force Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Supramolecular Self-Assembly in Materials
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Retinal Development and Disorders
- Pregnancy-related medical research
- Spinal Hematomas and Complications
- Mechanical and Optical Resonators
- Cholinesterase and Neurodegenerative Diseases
- Photochromic and Fluorescence Chemistry
- Computational Drug Discovery Methods
- Radiation Detection and Scintillator Technologies
- RNA Interference and Gene Delivery
- Nanofabrication and Lithography Techniques
- Near-Field Optical Microscopy
- Extracellular vesicles in disease
- Nuclear Receptors and Signaling
Weill Cornell Medicine
2019-2025
Cornell University
2009-2025
Konyang University
2024
Kim's Eye Hospital
2024
Harvard University
2024
Boston Children's Hospital
2024
Severance Hospital
2023
Yonsei University
2010-2023
University of Pittsburgh
2008-2023
Johns Hopkins University
2023
Mechanistic understanding of the endocytosis and intracellular trafficking nanoparticles is essential for designing smart theranostic carriers. Physico-chemical properties, including size, clustering surface chemistry regulate their cellular uptake transport. Significantly, even single could cluster intracellularly, yet state subsequent are not well understood. Here, we used DNA-decorated gold (fPlas-gold) as a dually emissive fluorescent plasmonic probe to examine states Evidence from...
Significance We describe the first, to our knowledge, integrated dynamic DNA nanotechnology and 2D material electronics overcome current limitations for detection of single-nucleotide polymorphism (SNP). Electrical has been advancing rapidly achieve high specificity, sensitivity, portability. However, actual implementation is still in infancy because low especially analytically optimal practically useful length target strands. Most research date focused on enhancement sensitivity biosensors,...
Abstract Electronic DNA‐biosensor with a single nucleotide resolution capability is highly desirable for personalized medicine. However, existing DNA‐biosensors, especially polymorphism (SNP) detection systems, have poor sensitivity and specificity lack real‐time wireless data transmission. DNA‐tweezers graphene field effect transistor (FET) are used SNP transmitted wirelessly analysis. Picomolar of quantitative achieved by observing changes in Dirac point shift resistance change. The use...
Integrins link the extracellular environment to actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside inside is essential. Single-molecule fluorescence dynamics show that ligand binding bent-closed integrin conformation, which predominates on surfaces, followed within milliseconds by two concerted changes, leg extension headpiece opening, give high-affinity conformation. The extended-closed conformation not an intermediate but can be directly...
Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors, moonlight as constitutively active phospholipid scramblases. The plasma metazoan cells is replete with GPCRs yet has strong resting trans-bilayer asymmetry, the lipid phosphatidylserine confined to cytoplasmic leaflet. To account for persistence this asymmetry in presence GPCR scramblases, we hypothesized that GPCR-mediated scrambling regulated by cholesterol, major constituent membrane. We now...
Calcific aortic valve disease is a leading cardiovascular in the elderly, and progressive calcification results failure of valvular function. Aortic interstitial cells (AVICs) from stenotic valves express higher levels bone morphogenetic protein-2 response to Toll-like receptor 4 stimulation. We recently found that interacts with Notch1 human AVICs. This study tests hypothesis promotes pro-osteogenic AVICs.AVICs isolated diseased expressed alkaline phosphatase after lipopolysaccharide The...
Amyloid β (Aβ) oligomers are the predominant toxic species in pathology of Alzheimer's disease. The prevailing mechanism for toxicity by Aβ includes ionic homeostasis destabilization neuronal cells forming ion channels. These channel structures have been previously studied model lipid bilayers. In order to gain further insight into interaction with natural membrane compositions, we examined and conductivities a composed brain total extract (BTLE). We utilized two complementary techniques:...
Research Article5 December 2017Open Access Transparent process The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology Ana Martinez Hernandez Department Epigenetics Systems Medicine Neurodegenerative Diseases, German Center Diseases (DZNE), Göttingen, Germany Genes Behavior, Max Planck Institute Biophysical Chemistry, Search more papers by this author Hendrik Urbanke Alan L Gillman orcid.org/0000-0002-1312-047X of...
The eight metabotropic glutamate receptors (mGluRs) serve critical modulatory roles throughout the nervous system. molecular diversity of mGluRs is thought to be further expanded by formation heterodimers, but co-expression mGluR subtypes at cellular level and relative propensities heterodimer are not well known. Here, we analyze single-cell RNA sequencing data find that cortical pyramidal cells express multiple with distinct profiles for different receptor combinations. We then develop...
Androgenetic alopecia (AGA) is a prevalent hair loss disorder with psychological repercussions. Traditional treatments have limitations, leading to the exploration of regenerative therapies such as exosomes derived from adipose tissue stem cells (ASC-Exosomes).
The cullin family of ubiquitin ligases can potentially assemble hundreds RING-type E3 complexes (CRLs) by utilizing different substrate receptors that share common interaction domains. Cullin dictate specificity, and cullin-mediated degradation controls a wide range cellular processes, including proliferation, differentiation, apoptosis. Dysregulation activity has been shown to contribute oncogenesis through the accumulation oncoproteins or excessive tumor suppressors. In this review, we...
Sulfonated rhodamine dyes allow SNAP- and Halo-tag labelling of cell surface protein fusions. A far-red version can be used for STED nanoscopy.
The metabotropic glutamate receptors (mGluRs) are family C, dimeric G protein–coupled (GPCRs), which play critical roles in synaptic transmission. Despite an increasing appreciation of the molecular diversity this family, how distinct mGluR subtypes regulated remains poorly understood. We reveal that different group II/III show markedly beta-arrestin (β-arr) coupling and endocytic trafficking. While mGluR2 is resistant to internalization mGluR3 shows transient β-arr coupling, enables...
The metabotropic glutamate receptors (mGluRs) are neuromodulatory family C G protein coupled which assemble as dimers and allosterically couple extracellular ligand binding domains (LBDs) to transmembrane (TMDs) drive intracellular signaling. Pharmacologically, mGluRs can be targeted at the LBDs by synthetic orthosteric compounds or TMDs allosteric modulators. Despite potential of therapeutics, an understanding functional structural basis their effects is limited. Here we use multiple...
Abstract Despite the widespread physiological roles of beta-arrestin (β-arr) coupling in G protein-coupled receptor (GPCR) regulation, molecular basis GPCR/β-arr interaction has been studied primarily monomeric family A GPCRs. Here we take an integrative biophysical and structural approach to uncover extreme diversity β-arr neuromodulatory metabotropic glutamate receptors (mGluRs), prototypical, dimeric C Using a new single molecule pulldown assay, find that mGluRs couple β-arrs with 2:1 or...
Impermeable SNAP-tag substrates allow exclusive labelling of receptors on the cell membrane for nanoscopy, SiMPull and <italic>in vivo</italic> use.
The kainate receptors (KARs) are members of the ionotropic glutamate receptor family and assemble into tetramers from a pool five subunit types (GluK1-5). Each confers distinct functional properties to receptor, but compositional stoichiometric diversity KAR is not well understood. To address this, we first solve structure GluK1 homomer, which enables systematic assessment structural compatibility among subunits. Next, analyze single-cell RNA sequencing data, reveal extreme in combinations...
Abstract Tobacco smoking increases the risk of intervertebral disc degeneration (IDD) and back pain, but mechanisms underlying adverse effects are largely unknown. Current hypotheses predict that contributes to IDD indirectly through nicotine‐mediated vasoconstriction which limits exchange nutrients between discs their surroundings. We alternatively hypothesize direct contact cells, is, cells in outermost annulus those present along fissures degenerating discs, with vascular system...