- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Cholinesterase and Neurodegenerative Diseases
- Prostate Cancer Diagnosis and Treatment
- Ion channel regulation and function
- Cancer, Lipids, and Metabolism
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- Ion Transport and Channel Regulation
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- Cancer, Hypoxia, and Metabolism
- Radiation Therapy and Dosimetry
- Protein Kinase Regulation and GTPase Signaling
- Urologic and reproductive health conditions
- Health Systems, Economic Evaluations, Quality of Life
- Drug Transport and Resistance Mechanisms
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Advanced Radiotherapy Techniques
- Spinal Dysraphism and Malformations
- Urological Disorders and Treatments
- Immune Cell Function and Interaction
- Bladder and Urothelial Cancer Treatments
- Mass Spectrometry Techniques and Applications
University of California, Los Angeles
2012-2023
Hauptman-Woodward Medical Research Institute
2021-2023
Ludwig-Maximilians-Universität München
2014
Weizmann Institute of Science
2007-2012
University of California System
2011
Barzilai Medical Center
2004-2011
East China University of Science and Technology
2009
Fudan University
2009
Louisiana State University Health Sciences Center Shreveport
2008
Asher Consulting (United States)
2007
In recent years, there has been a vast increase in structural and functional understanding of VDAC1, but VDAC2 -3 have understudied despite having many unique phenotypes. One reason for the paucity biochemical characterization isoforms stems from inability obtaining purified, protein. Here we demonstrate expression, isolation, basic zebrafish (zfVDAC2). Further, resolved structure zfVDAC2 at 2.8 Å resolution, revealing crystallographic dimer. The dimer orientation was confirmed solution by...
Abstract The biennial CASP experiment is a crucial way to evaluate, in an unbiased way, the progress predicting novel 3D protein structures. In this article, we assess quality of prediction template free models, that is, ab initio structures proteins based solely on amino acid sequences, did not have significant sequence identity any Protein Data Bank. There were 13 targets category and 102 groups submitted predictions. Analysis was GDT_TS analysis, which has been used previous experiments,...
β-Secretase (β-site amyloid precursor protein-cleaving enzyme 1; BACE1) is a transmembrane aspartic protease that cleaves the β-amyloid protein en route to generation of β-peptide (Aβ) believed be responsible for Alzheimer's disease cascade. It thus prime target development inhibitors which may serve as drugs in treatment and/or prevention disease. In following determination crystal structures both apo and complexed BACE1, structural analysis all BACE1 deposited PDB molecular dynamics (MD)...
Abstract Intrinsically unstructured proteins (IUPs), also known as natively unfolded proteins, lack well‐defined secondary and tertiary structure under physiological conditions. In recent years, growing experimental theoretical evidence has accumulated, indicating that many entire protein sequences are conditions, they play significant roles in diverse cellular processes. Bioinformatic algorithms have been developed to identify such for which structural data lacking, but still generate...
Many pathogenic bacteria utilise sialic acids as an energy source or use them external coating to evade immune detection. As such, that colonise sialylated environments deploy specific transporters mediate import of scavenged acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation SiaT, acid transporter from Proteus mirabilis. SiaT is secondary active the sodium solute symporter (SSS) family, which Na
Recruitment of intracellular vesicles containing the large GTPase CRACR2A to immunological synapse mediates T cell receptor signaling.
Abstract Purpose: OATP1B1 (SLCO1B1) is the most abundant and pharmacologically relevant uptake transporter in liver a key mediator of xenobiotic clearance. However, regulatory mechanisms that determine activity remain uncertain, as result, unexpected drug–drug interactions involving substrates continue to be reported, including several tyrosine kinase inhibitors (TKI). Experimental Design: OATP1B1-mediated overexpressing HEK293 cells hepatocytes was assessed presence FDA-approved TKIs, while...
Significance Transporters isomerize between conformations to shuttle cargo across membranes, but the mechanism is not understood. Double electron–electron resonance measurements on sodium-dependent sugar transporter (vSGLT) were used explore conformational state of under specific ligand conditions. Although transport by vSGLT driven sodium gradients, adopts an inward-open conformation irrespective presence sodium. In and galactose, transitions occluded conformation. We propose that cell’s...
Significance Site-directed fluorometry was used to understand conformational changes of the Na + /glucose symporter. SGLT1 functions by a mechanism where substrate-binding site alternates between two faces membrane, but little is known about underlying changes. Rhodamines were covalently inserted into substrate cavity, and fluorescence measured in real time with opening closing outer gate as driven inward outward conformations using voltage jumps. Structural modeling indicated that quenching...
Objective To assess the accuracy of radionuclide scrotal imaging (RSI) in diagnosis testicular torsion and appendages. Patients methods Eighty‐seven patients (mean age 30.1 years, range 8–65) who presented with acute pain were evaluated by RSI results correlated clinical surgical findings. Results Of 87 patients, 44 underwent exploration 42 treated conservatively. One patient a ‘missed torsion’ pattern on refused operation was lost to follow‐up. surgery, found 30 appendages 14 patients. The...
We assessed the results of transvesical prostatectomy in patients older than 80 years.We studied 98 to 90 years old who underwent between 1986 and 1993, including those with a large prostate (preoperative estimated weight more gm.), numerous or cystolithiasis bladder diverticulum, which are indications for open prostatectomy. Clinical data were obtained by chart review.The surgery urinary retention 53 (54%), severe obstructive symptoms 18 (18.4%), 17 (17.3%), prostatic bleeding 10 (10.2%)...
A bis-(−)-nor-meptazinol derivative in which the two meptazinol rings are linked by a nonamethylene spacer is novel acetylcholinesterase inhibitor that inhibits both catalytic activity and Aβ peptide aggregation. The crystal structure of its complex with Torpedo californica was determined to 2.7 Å resolution. ligand spans active-site gorge, one nor-meptazinol moiety bound at "anionic" subsite active site, disrupting triad forming hydrogen bond His440Nε2, hydrogen-bonded Ser200Oγ native...
Abstract Sodium-dependent glucose transporters (SGLTs) couple a downhill Na + ion gradient to actively transport sugars. Here, we investigate the impact of membrane potential on vSGLT structure and function using sugar uptake assays, double electron-electron resonance (DEER), electrostatic calculations, kinetic modeling. Negative potentials, as present in all cell types, shift conformational equilibrium towards an outward-facing conformation, leading increased rates. Electrostatic...
The photosensitizer, methylene blue (MB), generates singlet oxygen that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark, it reversibly. Binding is accompanied by a bathochromic absorption shift, used to demonstrate displacement other inhibitors interacting with catalytic "anionic" subsite (CAS), peripheral (PAS), or bridging them. MB noncompetitive inhibitor of TcAChE, competing reversible directed at both subsites, but single site involved in inhibition....
To describe the use of a new lymph-node revealing solution (LNRS) for detecting lymph node involvement in total cystectomy specimens from patients with locally confined invasive transitional cell carcinoma (TCC) bladder, and to compare results obtained those using conventional method (palpation sectioning perivesical fat) that may fail detect very small nodes.Of 12 TCC, six which 0-3 metastatic nodes were identified by further investigated LNRS. The comprised 95% ethanol, diethyl ether,...
Bladder carcinoma is the fourth most common cancer in men and eighth among women. Our study aimed to characterise tumour-associated antigen peptides of transitional cell bladder (TCC). A DNA micro-array-based differential display analysis 10 000 genes was carried out, MAGE-A8 gene expression detected tumour, not normal bladder. High occurrence observed fresh tumour samples (17 out 23) TCC lines (four eight). The protein sequence screened for HLA-A2.1-binding motifs, six potential were...
Db−/−xβ2 microglobulin (β2m) null mice transgenic for a chimeric HLA-A2.1/Db-β2m single chain (HHD mice) are an effective biological tool to evaluate the antitumour cytotoxic T-lymphocyte response of known major histocompatibility-restricted peptide tumour-associated antigens, and screen putative unknown novel peptides. We utilised HHD lymphocytes identify immunodominant epitopes colon carcinoma overexpressed genes. screened with HHD-derived over 500 HLA-A2.1-restricted peptides derived from...