A5040766930- 3D Printing in Biomedical Research
- Molecular Junctions and Nanostructures
- Advanced biosensing and bioanalysis techniques
- Cell Image Analysis Techniques
- Biosensors and Analytical Detection
- Cancer, Hypoxia, and Metabolism
- Crystallization and Solubility Studies
- Advanced Biosensing Techniques and Applications
- X-ray Diffraction in Crystallography
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Capillary Electrophoresis Applications
- Metabolomics and Mass Spectrometry Studies
- Enzyme function and inhibition
- Liver physiology and pathology
- Pluripotent Stem Cells Research
- Cancer Cells and Metastasis
- CO2 Reduction Techniques and Catalysts
- Mass Spectrometry Techniques and Applications
- ATP Synthase and ATPases Research
- Optical Imaging and Spectroscopy Techniques
- Mitochondrial Function and Pathology
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Electrochemical sensors and biosensors
University of North Carolina at Chapel Hill
2016-2025
UNC Lineberger Comprehensive Cancer Center
2017-2020
Communities In Schools of Orange County
2015-2019
Segeberger Kliniken
2017-2018
Harvard University
2011-2016
University of Wisconsin–Madison
2006-2012
Energy Center of Wisconsin
2009
University of California, Irvine
2008
The hydrophobic effect--a rationalization of the insolubility nonpolar molecules in water--is centrally important to biomolecular recognition. Despite extensive research devoted effect, its molecular mechanisms remain controversial, and there are still no reliably predictive models for role protein-ligand binding. Here we describe a particularly well-defined system protein ligands--carbonic anhydrase series structurally homologous heterocyclic aromatic sulfonamides--that use characterize...
The mechanism (or mechanisms) of enthalpy-entropy (H/S) compensation in protein-ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) which hypotheses ligand can be readily tested. Here we describe a particularly well-defined system protein ligands--human carbonic anhydrase (HCA) series benzothiazole sulfonamide ligands with different patterns fluorination--that use to define enthalpy/entropy this thermodynamically structurally....
ONC201 is a first-in-class imipridone molecule currently in clinical trials for the treatment of multiple cancers. Despite enormous potential, mechanism action controversial. To investigate and identify compounds with improved potency, we tested series novel analogues (TR compounds) effects on cell viability stress responses breast other cancer models. The TR were found to be ∼50–100 times more potent at inhibiting proliferation inducing integrated response protein ATF4 than ONC201. Using...
In vitro models of ischemia have not historically recapitulated the cellular interactions and gradients molecules that occur in a 3D tissue. This work demonstrates paper-based culture system mimics some among populations cells heart during ischemia. Multiple layers paper containing cells, suspended hydrogels, are stacked to form layered model Mass transport oxygen glucose into this can be modulated induce an ischemic environment bottom stack. stress induces cardiomyocytes at stack secrete...
Organosulfates have been proposed as contributors to aerosol growth and detected in both chamber atmospheric samples. We present a simple method for the synthesis of quantitative analytical standards two small hydroxycarboxylic acid-derived organosulfates, glycolic lactic acid sulfate. Additionally, we discuss stability organosulfates their previously sulfate hemiacetal isomers commonly used solvents filter extraction. The were found be stable under acidic conditions comparable those ambient...
Molecular rectification is a particularly attractive phenomenon to examine in studying structure-property relationships charge transport across molecular junctions, since the tunneling currents same junction are measured, with only change sign of bias, electrodes, molecule(s), and contacts. This type experiment minimizes complexities arising from measurements current densities at one polarity using replicate junctions. paper describes new organic rectifier: having structure...
This paper uses the binding pocket of human carbonic anhydrase II (HCAII, EC 4.2.1.1) as a tool to examine properties Hofmeister anions that determine (i) where, and how strongly, they associate with concavities on surfaces proteins (ii) how, upon binding, alter structure water within those concavities. Results from X-ray crystallography isothermal titration calorimetry show most HCAII by forming inner-sphere ion pairs Zn(2+) cofactor. In these pairs, free energy anion-Zn(2+) association is...
Eleven 2,2'-bipyridine (bpy) ligands functionalized with attachment groups for covalent immobilization on silicon surfaces were prepared. Five of the feature silatrane functional to metal oxide coatings surfaces, while six contain either alkene or alkyne hydrogen-terminated surfaces. The bpy coordinated Re(CO)5Cl form complexes type Re(bpy)(CO)3Cl, which are related known catalysts CO2 reduction. Six new characterized using X-ray crystallography. As proof principle, four molecular Re...
Recent studies have demonstrated that carbon, in the form of diamond, can be functionalized with molecular and/or biomolecular species to yield interfaces exhibiting extremely high stability and selectivity binding target biomolecules solution. However, diamond most other crystalline forms carbon involve high-temperature deposition or processing steps restrict their ability integrated materials. Here, we demonstrate photochemical functionalization amorphous films followed by covalent...
This paper describes a method for determining the density of contact trace objects with magnetic levitation (MagLev). MagLev measurements accurately determine (± 0.0002 g/cm(3) ) diamagnetic object and are compatible that nonuniform in shape size. The device (composed two permanent magnets like poles facing) described provide means objects. is inexpensive, rapid, verifiable provides numerical values--independent specific apparatus or analyst--that correspond to absolute sample may be entered...
This paper describes a method to detect the presence of bacteria in aqueous samples, based on capture syringe filter, and infection targeted bacterial species with bacteriophage (phage). The use phage as reagent provides two opportunities for signal amplification: (i) replication inside live host (ii) delivery expression complementing gene that turns enzymatic activity produces colored or fluorescent product. Here we demonstrate phage-based amplification scheme an M13KE delivers small...
Semiconductor photoelectrodes are regularly coupled to solid-state heterogeneous catalysts perform solar-driven reduction of CO2. Less frequently, molecular employed better control the reactivity toward desired products, yet development robust semiconductor/molecule interfaces has proven challenging. Here, we demonstrate that a 2-3 nm thermal oxide layer on Si exhibits stability in aqueous solution, high photovoltage, and photocurrent density ∼10 mA/cm2 for photoelectrochemical homogeneous...
Abstract Per- and polyfluoroalkyl substances (PFAS) are “forever chemicals” pervasive environmental contaminants associated with cancer. Epidemiological studies found that an increased incidence of hormone-sensitive breast cancer is correlated PFAS exposure. Cell-based assays provide a well-controlled experimental platform to quantify cellular responses as function Given the nearly 15,000 known on Environmental Protection Agency's toxicity database (DSSTox), in vitro models only feasible...
A tetrafluorophenyl (TFP) ester-terminated self-assembled monolayer (SAM) for the fabrication of DNA arrays on gold surfaces is described. Activated ester SAMs are desirable biomolecule array because they readily react with amine-containing molecules to form a stable amide linkage. N-Hydroxysuccinimide (NHS) commonly used this purpose but subject competing hydrolysis side reaction, limiting their effectiveness under basic conditions. TFP was evaluated here as an alternative activated leaving...
Surface plasmon resonance (SPR) imaging affords label-free monitoring of biomolecule interactions in an array format. A surface conducting metal thin film is required for SPR measurements. Gold films are traditionally used experiments as they readily functionalized with thiol-containing molecules through formation a gold−sulfur bond. The lability this gold−thiol linkage upon exposure to oxidizing conditions and ultraviolet light renders these surfaces incompatible light-directed synthetic...
It's the water that matters. Pairs of benzo- and perfluorobenzoarylsulfonamide ligands bind to human carbonic anhydrase with a conserved binding geometry, an enthalpy-driven binding, indistinguishable affinities (see picture). These data support pervasive theory lock-and-key model disregards important component binding: water, which fills pocket protein surrounds ligand. As service our authors readers, this journal provides supporting information supplied by authors. Such materials are peer...
Cellular migration is the movement of cells, cultured as a monolayer; cellular invasion similar to migration, but requires cells move through three-dimensional material such basement membrane extract or synthetic hydrogel. Migration assays, transwell assay, are widely used study because they amenable high-throughput screens with minimal experimental setup. These assays offer limited information about responses gradients in vivo oversimplify threedimensional (3D) environment tissue. There...
Paper-based cultures are an emerging platform for preparing 3D tissue-like structures. Chemical gradients can be imposed upon these cultures, generating microenvironments similar to those found in poorly vascularized tumors. There is increasing evidence that the tumor microenvironment responsible promoting drug resistance and increased invasiveness. Acidosis, or acidification of extracellular space, particularly important aggressive cancer phenotypes. To better understand how cells respond...
Paper-based scaffolds support the three-dimensional culture of mammalian cells in tissue-like environments. These Tissue Papers, a name that highlights use materials obtained from (plant) tissue to generate newly functioning (human) structures, are promising analytical tool quantify cellular responses physiologically relevant extracellular gradients and coculture architectures. Here, we highlight current examples commonly used methods analysis, measurement challenges.
Cellular movement is essential in the formation and maintenance of healthy tissues as well disease progression such tumor metastasis. In this work, we describe a paper-based Transwell assay capable quantifying cellular invasion through an extracellular matrix. The assays generate similar datasets, with equivalent reproducibility, to commercially available assays. With different culture configurations, quantify invasion: upon addition exogenous factor or presence medium obtained from other...
Paper-based scaffolds are an attractive material for culturing mammalian cells in a three-dimensional environment. There number of previously published studies, which utilize these to generate models aortic valves, cardiac ischemia and reperfusion, solid tumors. These have largely relied on fluorescence imaging microscopy quantify the scaffolds. We present here polymerase chain reaction (PCR)-based method, capable quantifying multiple cell types single culture with aid DNA barcodes: unique...