Ming-Hui Wei
A5110097272- Renal cell carcinoma treatment
- Hormonal Regulation and Hypertension
- Renal and related cancers
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Tuberous Sclerosis Complex Research
- Genetic and Kidney Cyst Diseases
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Plant Reproductive Biology
- Axon Guidance and Neuronal Signaling
- Genetic Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- Pancreatic function and diabetes
- Polyamine Metabolism and Applications
- Cardiac electrophysiology and arrhythmias
- Neurogenesis and neuroplasticity mechanisms
- Skin and Cellular Biology Research
- Dermatological and Skeletal Disorders
- Ion channel regulation and function
- Genomics and Chromatin Dynamics
National Cancer Institute
1998-2024
National Institutes of Health
1998-2016
Center for Cancer Research
2004-2016
Division of Cancer Epidemiology and Genetics
2003-2011
Science Applications International Corporation (United States)
1998-2008
Frederick National Laboratory for Cancer Research
2004
National Cancer Institute
2003
The University of Texas Southwestern Medical Center
1998
To discover genes involved in von Hippel-Lindau (VHL)-mediated carcinogenesis, we used renal cell carcinoma lines stably transfected with wild-type VHL-expressing transgenes. Large-scale RNA differential display technology applied to these identified several differentially expressed genes, including an alpha carbonic anhydrase gene, termed CA12 . The deduced protein sequence was classified as a one-pass transmembrane CA possessing apparently intact catalytic domain the extracellular module....
Rationale: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to fibrofolliculomas, kidney neoplasms, lung cysts, and spontaneous pneumothorax.Objectives: We evaluated 198 patients from 89 families with BHDS characterize the risk factors for pneumothorax genotype–pulmonary associations.Methods: Helical computed tomography scans of chest were used screen pulmonary abnormalities. BHD mutation data associations. examined relationship categorical...
In follow-up of a recent genome-wide association study (GWAS) that identified locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted fine mapping analysis 120 kb region includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) 2278 RCC and 3719 controls European background observed novel signal rs9679290 [P = 5.75 × 10−8, per-allele odds ratio (OR) 1.27, 95% confidence interval (CI): 1.17–1.39]. Imputation SNPs surrounding using...
Abstract Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited syndrome caused by germline pathogenic variants in the fumarate hydratase (FH) gene. Affected individuals are at risk for developing cutaneous uterine leiomyomas aggressive FH-deficient carcinoma (RCC) with a papillary histology. Due to disrupted tricarboxylic acid cycle, kidney cancers rely on aerobic glycolysis energy production, potentially creating compensatory metabolic vulnerabilities. This study conducted...
<p>NAD<sup>+</sup> and NADH analysis of UOK365 cells. Analysis the relative levels NAD<sup>+</sup> their ratio after 24 hour treatment cell line model with a range concentrations (0.5-100 nM) either GNE-618 (A-B) or OT-82 (C-D). All were compared to cells treated amount DMSO present in highest concentration utilized drugs.</p>
<p>Real-time invasion analysis of UOK262 and UOK365 cells treated with OT-82. Real-time demonstrating cell line over 5 days (120 hrs) was performed (A) to show that DMSO (used as the vehicle for OT-82) did not affect in comparison untreated (B) demonstrate effects OT-82 treatment at either 1 nM or 10 alone (DMSO) non-invasive control (no serum lower chamber). In each case, a representative graph from one three separate experiments is shown. (C) The inhibition repeats dose shown line....
<p>In vitro analysis of NAMPT inhibition on glycolysis in FH-deficient tumor cells. (A) Effects the inhibitor OT-82 (100 nM) extracellular acidification rate (ECAR) UOK262 and UOK365 HLRCC cell lines RPTEC normal line. (B) Representation different effects versus DMSO at time point 5 (designated by a star) after injection glucose UOK262, UOK365, RPTEC. 2-DG, 2-deoxyglucose.</p>
<p>Structural figures of NAMPT inhibitors.</p>
<p>In vivo effects of NAMPT inhibitors in HLRCC xenograft models. Mean body weights are constant throughout the drug study for animals harboring UOK262 xenografts (A) and UOK365 (B; shown Figure 3A-B, <i>n</i> = 10 mice per arm, 95mg/kg OT-82 8 week duration). (C-D) H&E stained sections retinas obtained from NSG treated with vehicle or 5 days. (E-F) Caspase 3 95 mg/kg Histological were evaluated signs retinal toxicity by a trained veterinary pathologist. No overt...
<div>Abstract<p>Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited syndrome caused by germline pathogenic variants in the fumarate hydratase (<i>FH</i>) gene. Affected individuals are at risk for developing cutaneous uterine leiomyomas aggressive FH-deficient carcinoma (RCC) with a papillary histology. Due to disrupted tricarboxylic acid cycle, kidney cancers rely on aerobic glycolysis energy production, potentially creating compensatory metabolic...
<p>Expression levels of NAD<sup>+</sup> biosynthetic and salvage pathway genes in HLRCC tumors, normal kidney samples pan-kidney data from TCGA. (A) Overview pathways. (B-E) Box plots for selected NAD+ derived RNA-seq analysis tumors specimens. (F) TCGA data. NAMPT (nicotinamide phosphoribosyltransferase), NAPRT (nicotinate phosphoribosyltransferase ), QPRT (quinolinate NMNAT mononucleotide adenylyl transferase), KIRP (kidney renal papillary cancer), CIMP (CpG island...
<p>Validation studies to evaluate inhibition of additional HLRCC cell lines by NAMPT inhibitors. A) Effects the inhibitor GNE-618 on viability in FH <sup>-/</sup>- cells UOK348, UOK271, UOK350, UOK268, UOK365, restored UOK268WT and non-transformed kidney epithelial RPTEC. Cell was assessed Titer-Glo assay at 96 h. B) OT-82 -/- RPTEC.</p>
<p>Proliferation analysis of UOK268 and RPTEC in response to OT-82 nicotinic acid rescue NAD<sup>+</sup>/NADH depletion. (A-B) or cells were grown 96 well plates from an initial plating 2,000 cellular confluency was monitored real-time by Incucyte S3 Live-Cell Imaging System. After 24 hours measurements treated with either DMSO, 1 nM OT-82, 5 10 plus mM nicotinamide mononucleotide (NMN) evaluated for additional days. (C-D) The effect NMN on depletion is shown. (E) Effects...
<p>Cell proliferation rates of HLRCC cell lines treated with low and high concentrations NAMPT inhibitors. A) Effect OT-82 at 0.8nM or 100nM (left) GNE-618 8nM 200nM (right) on UOK262 after 96 hours. B) UOK268 C) UOK365 hours.</p>
<p>HLRCC spheroid characterization and OT-82 effect on 3D culture. A) UOK262 (B) UOK365 spheroids plated at different cell densities (8000, 4000, 2000 cells/well in triplicate) after 24h, showing degrees of aggregation. Cell viability (C) (D) treated with GNE-618 (1 nM-500 nM) or (0.2 nM-100 assessed Cell-Titer Glo assay decreases a dose dependent manner.</p>
<p>Time course study design for imaging and OT-82 treatment hyperpolarized pyruvate 13C-MRSI. Post MRSI was performed 5 hours post dose #2.</p>
<p>Pharmacokinetic profile of OT-82 in nude and NSG mice. (A) Bioanalysis plasma concentrations were made using a validated LC-MS/MS assay (<i>n</i>=3 mice, 50 mg/kg, 7 intervals; <i>n</i>=3 75mg/kg, intervals). (B) Pharmacokinetic parameters calculated after single dose OT-82. The data from all mice each group pooled together to assume one “average” mouse per group.</p>
<p>NAMPT immunohistochemical analysis in HLRCC tumors and normal kidney. (A) In patient #1, both a primary kidney tumor (upper panel) an associated metastatic mass (lower demonstrated strong NAMPT staining. Surrounding non-tumor tissues show little (B) #4, shows staining comparison to tissue present on the same slide panel). (C) #5, Material from this was used derive UOK262 cell line, which similar positive when grown as xenograft (D) #6, Matching H&E is included for all samples...
A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed verified. suite programs, collectively called pompous (polymorphic marker ubiquitous simple sequences) detects tandem repeats ranging dinucleotides up to 250 mers, scores them according predicted level polymorphism, designs appropriate flanking primers PCR amplification. This approach validated on an approximately 750-kilobase region chromosome 3p21.3, involved in...
Germline H255Y and K508R missense mutations in the folliculin (FLCN) gene have been identified patients with bilateral multifocal (BMF) kidney tumours clinical manifestations of Birt-Hogg-Dubé (BHD) syndrome, or BMF as only manifestation; however, their impact on FLCN function remains to be determined. In order determine if promote aberrant cell proliferation leading pathogenicity, we generated mouse models expressing these mutants using BAC recombineering technology investigated ability...