A5108047351- Alzheimer's disease research and treatments
- Supramolecular Self-Assembly in Materials
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Photoreceptor and optogenetics research
- Photochromic and Fluorescence Chemistry
- Machine Learning in Bioinformatics
- Luminescence Properties of Advanced Materials
- Neuroscience and Neuropharmacology Research
- Barrier Structure and Function Studies
- Neurological Disease Mechanisms and Treatments
- Antimicrobial Peptides and Activities
- Sperm and Testicular Function
- Ion channel regulation and function
- Marine Biology and Environmental Chemistry
- HIV Research and Treatment
- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
- Advanced NMR Techniques and Applications
- Pain Mechanisms and Treatments
- Solid State Laser Technologies
- Heat shock proteins research
- Retinal Development and Disorders
- Phosphodiesterase function and regulation
- Biochemical and Structural Characterization
Center for Drug Evaluation and Research
2019-2025
Icahn School of Medicine at Mount Sinai
2019-2024
Anhui Agricultural University
2024
United States Food and Drug Administration
2019-2022
National Institutes of Health
2002-2021
National Institute of Mental Health
2014-2021
National Cancer Institute
2019
National Institute on Deafness and Other Communication Disorders
2015-2018
Sun Yat-sen University
2018
South China University of Technology
2016-2017
The misfolding and aggregation of β-amyloid peptides (Aβ) into amyloid fibrils, a process that has been pathologically linked to the onset Alzheimer's disease, is dependent on presence heterogeneous surface (e.g., cell membrane). Understanding kinetics fibril formation associated structural transition from monomers intermediates eventually fibrils critical for development viable therapeutic agents. In this work, using circular dichroism (CD), atomic force microscopy (AFM), plasmon resonance...
The rapid rise of antibiotic resistance in pathogens becomes a serious and growing threat to medicine public health. Naturally occurring antimicrobial peptides (AMPs) are an important line defense the immune system against invading bacteria microbial infection. In this work, we present combined computational experimental study biological activity membrane interaction computationally designed Bac2A-based peptide library. We used MARTINI coarse-grained molecular dynamics with adaptive biasing...
Human islet amyloid polypeptide (hIAPP or amylin) is a causative agent in pancreatic deposits found patients with type 2 diabetes. The aggregation of full-length hIAPP(1-37) into small oligomeric species increasingly believed to be responsible for cell dysfunction and death. However, rat IAPP (rIAPP(1-37)), which differs from hIAPP only six 37 residues, loses its ability form toxic species. Atomic details the effect sequence on structure toxicity between amyloidogenic, peptide...
Tight junctions consist of a network sealing strands that create selective ion permeability barriers between adjoining epithelial or endothelial cells. The current model for tight junction consists paired rows claudins (Cldn) coupled by cis interface (X-1) derived from crystalline Cldn15. Here we show exhibit broad range lateral bending, indicating diversity in interactions. By combining protein-protein docking, coevolutionary analysis, molecular dynamics, and mutagenesis screen, identify...
We have developed a photochemical protecting group that enables wavelength selective uncaging using green versus violet light. Change of the exocyclic oxygen laser dye coumarin-102 to sulfur, gave thio-coumarin-102, new chromophore with an absorption ratio at 503/402 nm 37. Photolysis thio-coumarin-102 caged γ-aminobutyric acid was found be highly on neurons, normalized electrical responses >100-fold higher in channel. When partnered glutamate, we could use whole cell and irradiation fire...
The misfolding and aggregation of amyloid-β (Aβ) peptides into amyloid fibrils in solution on the cell membrane has been linked to pathogenesis Alzheimer's disease. Although it is well-known that presence different surfaces can accelerate Aβ fibrils, surface-induced conformation, orientation, aggregation, adsorption have not well understood at atomic level. Here, we perform all-atom explicit-water molecular dynamics (MD) simulations study orientation change, conformational dynamics, surface...
Accumulation of small soluble oligomers amyloid-β (Aβ) in the human brain is thought to play an important pathological role Alzheimer's disease. The interaction these Aβ with cell membrane and other artificial surfaces for understanding aggregation toxicity mechanisms. Here, we present a series exploratory molecular dynamics (MD) simulations study early adsorption conformational change from dimer hexamer on three different self-assembled monolayers (SAMs) terminated CH(3), OH, COOH groups....
The number of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in synapses determines synaptic strength. AMPAR expression can be regulated locally dendrites by activity. mechanisms activity-dependent local regulation expression, however, remain unclear. Here, we tested whether microRNAs (miRNAs) are involved N-methyl-d-aspartate (NMDA) receptor (NMDAR)–dependent expression. We used the 3′ untranslated region Gria1, which encodes AMPA subunit GluA1, to pull down miRNAs...
Associative learning and memory are essential to logical thinking cognition. How the neurons recruited as associative cells encode multiple input signals for their associated storage distinguishable retrieval remains unclear. We studied this issue in barrel cortex by vivo two-photon calcium imaging, electrophysiology neural tracing our mouse model that simultaneous whisker olfaction stimulations led odorant-induced motion. After cross-modal reflex arose, piriform cortices connected. More...
Azobenzenes are the most widely studied photoswitches, and have become popular optical probes for biological systems. The cis configuration is normally metastable, meaning trans always thermodynamically favored. unique exception to this rule an azobenzene having a two-carbon bridge between ortho positions, substitutions that lock photoswitch in its configuration. Only thoroughly chemically characterized relatively recently, we describe first applications of locked-azobenzene (or "LAB")...
Immune check point inhibitors targeting programmed cell death protein-1 (PD-1) and its ligand (PD-L1) have shown clinical success in treatment of human malignancies. Triple negative breast cancer (TNBC), which is primarily characterized by high heterogeneity presence tumor infiltrating lymphocytes, remains therapeutic challenge due to unavailability approved targeted therapy. Therapeutic potential immune for TNBC patients under active investigation. In this study, we show that FDA-approved...
Alzheimer's disease is characterized by the extracellular deposition of beta-amyloid peptide (Abeta) in cerebral plaques and evidence accumulating that amyloid neurotoxic. Abeta derived from precursor protein (APP). Proteolytic processing APP enzyme, beta-secretase, produces N terminus Abeta, releases a secreted ectodomain (beta-s-APP). To develop animal models for measuring beta-secretase activity specific brain cells vivo, we have targeted expression full-length human to either neurons or...
The ability of peptides to construct specific secondary structures provides a useful function for biomaterial design that cannot be achieved with traditional organic molecules and polymers. Inhibition amyloid formation is promising therapeutic approach the treatment neurodegenerative diseases. Existing peptide-based inhibitors are mainly derived from original sequences, which have very limited sequence diversity activity. It highly desirable explore other not directly sequences. Here, we...
The adsorption and aggregation of the amyloid-β (Aβ) peptides on cell membrane plays a causal role in pathogenesis Alzheimer's disease. Here, we report all-atom molecular dynamics (MD) simulations to study interactions Aβ oligomer with self-assembled monolayers (SAMs) terminated hydrophobic CH3 hydrophilic OH functional groups, particular interests how surface chemistry orientation affect behavior Aβ. Simulation results show that CH3-SAM has stronger binding affinity than OH-SAM does,...
A 37-residue of human islet amyloid polypeptide (hIAPP or amylin) is a main component plaques found in the pancreas ∼90% type II diabetes patients. It reported that hIAPP oligomers, rather than mature fibrils, are major toxic species responsible for pancreatic β-cell dysfunction and even cell death, but molecular structures these oligomers remain elusive. In this work, on basis recent solid-state NMR mass-per-length (MPL) data, we model series with different β-layers (one, two, three...
Nerve cells program the brain codes to manage well-organized cognitions and behaviors. It remains unclear how a population of neurons astrocytes work coordinately encode their spatial temporal activity patterns in response frequency intensity signals from sensory inputs.With two-photon imaging electrophysiology record cellular functions barrel cortex vivo, we analyzed whisker stimuli with increasing frequency, an environmental stimulus pattern that rodents experience accelerated motion....