A5056524627- Cancer, Hypoxia, and Metabolism
- Cholinesterase and Neurodegenerative Diseases
- Metabolism, Diabetes, and Cancer
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Amino Acid Enzymes and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Pancreatic function and diabetes
- Pesticide Exposure and Toxicity
- Adipose Tissue and Metabolism
- Liver physiology and pathology
- Cellular transport and secretion
- Colorectal Cancer Screening and Detection
- Enzyme function and inhibition
- Cancer-related Molecular Pathways
- Metabolism and Genetic Disorders
- Retinal and Optic Conditions
- Liver Disease and Transplantation
- Retinal Imaging and Analysis
- Endoplasmic Reticulum Stress and Disease
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
Technion – Israel Institute of Technology
2018-2024
Louisiana State University in Shreveport
2023
Tweed Shire Council
2020
Cancer Research UK Scotland Institute
2011-2013
Weizmann Institute of Science
2010-2012
Hebrew University of Jerusalem
2007-2008
Hadassah Medical Center
1972
A glycine- and leucine-based tripeptide improves symptoms in a mouse model of nonalcoholic fatty liver disease, which lacks approved treatments.
Lower circulating levels of glycine are consistently reported in association with cardiovascular disease (CVD), but the causative role and therapeutic potential atherosclerosis, underlying cause most CVDs, remain to be established. Here, following identification reduced patients significant coronary artery (sCAD), we investigated a atherosclerosis by modulating availability atheroprone mice. We further evaluated atheroprotective DT-109, recently identified glycine-based compound dual...
Abstract Inhibition of the epidermal growth factor receptor (EGFR) shows clinical benefit in metastatic colorectal cancer (CRC) patients, but KRAS-mutations are known to confer resistance. However, recent reports highlight EGFR as a crucial target be co-inhibited with RAS inhibitors for effective treatment KRAS mutant CRC. Here, we investigated tumor cell-intrinsic contribution G12D tumors by establishing murine CRC organoids key mutations (KRAS, APC, TP53) and inducible deletion....
Abstract Changes in protein subdomains through alternative splicing often modify protein‐protein interactions, altering biological processes. A relevant example is that of the stress‐induced up‐regulation acetylcholinesterase (AChE‐R) splice variant, a common response various tissues. In germ cells male transgenic TgR mice, AChE‐R excess associates with reduced sperm differentiation and counts. To explore mechanism(s) by which affects spermatogenesis, we identified AChE‐R's partners yeast...
Male infertility is often attributed to stress. However, the protein or proteins that mediate stress-related are not yet known. Overexpression of "readthrough" variant acetylcholinesterase (AChE-R) involved in cellular stress response a variety mammalian tissues. Here, we report testicular overexpression AChE-R heads, but tails, postmeiotic spermatozoa from mice subjected transient psychological compared with age-matched control mice. Transgenic overexpressing displayed reduced sperm counts,...
Non-alcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Understanding metabolic pathways involved can provide insights into progression. Untargeted metabolomics livers from mice with early-stage steatosis indicated a decrease in methylated metabolites suggesting altered carbon metabolism. The levels glycine, central component metabolism, were lower steatotic mice, line clinical evidence. Isotope tracing studies demonstrated that increased synthesis...
Abstract Aim Identifying elements associated with advanced colorectal cancer (CRC) stage may inform understanding of whether disease is a corollary access to healthcare or tumour biology and in turn allow the use targeted screening awareness programmes. The aim this study was identify factors that predict CRC at presentation Australia New Zealand. Method This cross‐sectional registry sourced from prospectively maintained Binational Colorectal Cancer Audit database primary outcome as defined...
Increasing evidence suggests an important role for amino acid metabolism in atherosclerotic cardiovascular disease (ASCVD), highlighting potential biomarkers, causative factors, and therapeutic targets. Among all acids, lower circulating glycine is consistently reported to be associated with enhanced ASCVD severity. The serine the main precursor glycine, a glycine:serine ratio more advanced unstable plaques. mitochondrial hydroxymethyltransferase 2 (SHMT2) catalyzes bulk of formation from...
While the role of lipids in atherosclerotic cardiovascular disease (ASCVD) is well studied, contribution amino acids becoming increasingly recognized. We and others reported that ratio glycine to serine reduced association with ASCVD severity. Primarily expressed liver, hydroxymethyltransferase 2 (SHMT2) thought be responsible for bulk biosynthesis from serine. recently reversed SHMT2 activity fatty livers drives depletion ( Ghrayeb et al. Cell Metab 2024 ). Nevertheless, whether regulation...
Abstract Under the low oxygen and lipid-depleted conditions, often encountered in tumor microenvironment, acetate is used as nutrient by cancer cells for biosynthesis of fatty acids. ACSS2, enzyme responsible capture within cell its conversion into Acetyl-CoA, upregulated under metabolically stressed conditions silencing shown to inhibit growth xenografts. Two independent HTS campaigns identified same small molecule ACSS2 inhibitor series that exhibited uncompetitive binding behavior respect...