A5055140288- Calcium signaling and nucleotide metabolism
- Ion Channels and Receptors
- PARP inhibition in cancer therapy
- Adenosine and Purinergic Signaling
- Sirtuins and Resveratrol in Medicine
- Toxin Mechanisms and Immunotoxins
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Parasitic Infections and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Reservoir Engineering and Simulation Methods
- Hydraulic Fracturing and Reservoir Analysis
- Gastric Cancer Management and Outcomes
- Coccidia and coccidiosis research
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
- Signaling Pathways in Disease
- SARS-CoV-2 and COVID-19 Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Cellular transport and secretion
- Prosthetics and Rehabilitation Robotics
Peking University
2016-2025
Chinese University of Hong Kong, Shenzhen
2021-2025
University of British Columbia
2025
Wuhan University of Technology
2025
Chinese University of Hong Kong
2009-2024
First People's Hospital of Yunnan Province
2024
Xuzhou Medical College
2024
Knexus Research (United States)
2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2008-2024
Shanxi Agricultural University
2022-2024
Abstract SARS-CoV-2 is the pathogen responsible for COVID-19 pandemic. The papain-like cysteine protease (PLpro) has been implicated in playing important roles virus maturation, dysregulation of host inflammation, and antiviral immune responses. multiple functions PLpro render it a promising drug target. Therefore, we screened library approved drugs also examined available inhibitors against PLpro. Inhibitor GRL0617 showed vitro IC 50 2.1 μM an effective inhibition cell-based assays....
SARM1, an NAD-utilizing enzyme, regulates axonal degeneration. We show that CZ-48, a cell-permeant mimetic of NMN, activated SARM1 in vitro and cellulo to cyclize NAD produce Ca
The identification of two forms a transmembrane enzyme suggests that flipping the catalytic domain from outside to inside cell may regulate its activity.
Peptide modulators targeting protein–protein interactions (PPIs) exhibit greater potential than small-molecule drugs in several important aspects including facile modification and relative large contact surface area. Stabilized peptides constructed by variable chemistry methods improved peptide stability cell permeability compared to that of the linears. Herein, we designed a stabilized peptide-based proteolysis-targeting chimera (PROTAC) estrogen receptor α (ERα) tethering an N-terminal...
The S4 transmembrane segments of voltage-gated ion channels move outward on depolarization, initiating a conformational change that opens the pore, but mechanism movement is unresolved. One structural model predicts sequential formation pairs between gating charges and negative in neighboring S2 S3 during gating. Here, we show paired cysteine substitutions for third charge (R3) D60 bacterial sodium channel NaChBac form disulfide bond activation, thus "locking" segment inducing slow...
CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be good target for immunotherapy of the disease. CD38 also signaling enzyme responsible metabolism two novel calcium messenger molecules. To able this multifunctional protein, we generated series nanobodies against with high affinities. Crystal structures complexes were solved, identifying three separate epitopes on carboxyl domain. Chromobodies,...
Chimeric antigen receptor T cells (CAR-Ts) are a promising strategy for the treatment of many cancers, including multiple myeloma (MM), hematological malignancy characterized by high expression CD38. To broaden applications using CD38 as therapeutic target disease, we developed new nanobody against and constructed CD38-CAR that was composed this targeting domain, 4-1BB CD3ζ costimulatory activating domains, in lentiviral vector. CD3+ from healthy individuals were transduced with at an...
cADPR is a well-recognized signaling molecule by modulating the RyRs, but considerable debate exists regarding whether can bind to and gate TRPM2 channel, which mediates oxidative stress in diverse physiological pathological processes. Here, we show that purified evoked channel currents both whole-cell cell-free single-channel recordings specific binding of NUDT9-H domain surface plasmon resonance. Furthermore, combining computational modeling with electrophysiological recordings, channels...
The cell surface ecto-enzyme CD38 is a promising target antigen for the treatment of hematological malignancies, as illustrated by recent approval daratumumab multiple myeloma. Our aim was to evaluate potential CD38-specific nanobodies novel diagnostics malignancies. We successfully identified 22 nanobody families using phage display technology from immunized llamas. Crossblockade analyses and in-tandem epitope binning revealed that recognize three different non-overlapping epitopes, with...
SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed synthesized fluorescent conjugates of styryl derivative with pyridine to serve as substrates SARM1, which exhibited large red shifts after conversion. With the conjugates, activation was visualized in live cells following elevation endogenous NMN or treatment cell-permeant NMN-analog. In neurons, imaging documented mouse preceded vincristine-induced by...
We recently showed that ischemia/reperfusion (I/R) of the heart causes CD38 activation with resultant depletion cardiac NADP(H) pool, which is most marked in endothelium. This was shown to limit production nitric oxide by endothelial synthase (eNOS), requires NADPH for production, resulting greatly altered function. Therefore, intervention inhibitors could reverse postischemic eNOS-mediated dysfunction. Here, we evaluated potency inhibitor luteolinidin, an anthocyanidin, at blocking activity...
CD38 catalyzes the synthesis of Ca2+ messenger, cyclic ADP-ribose (cADPR). It is generally considered to be a type II protein with catalytic domain facing outside. How it can catalyze intracellular cADPR that targets endoplasmic stores has not been resolved. We have proposed also exist in an opposite III orientation its cytosol. Here, we developed method using specific nanobodies immunotarget two different epitopes simultaneously on and firmly established naturally occurring human multiple...
Tyrosine is decarboxylated to tyramine by TYDC (Tyrosine decarboxylase) and then hydroxylated dopamine, which involved in plant response abiotic stress. However, little known about the function of MdTyDc alkaline stress plants. In our study, it was found that expression induced Therefore, apple plants overexpressing treated with alkali stress, we played an important role plants’ resistance Our results showed restriction on growth, decrease membrane permeability accumulation Na + were...