A5045163182- Advanced NMR Techniques and Applications
- Amino Acid Enzymes and Metabolism
- Enzyme Structure and Function
- Cancer, Hypoxia, and Metabolism
- Enzyme function and inhibition
- Chemical Reactions and Isotopes
- Epigenetics and DNA Methylation
- Electron Spin Resonance Studies
- Solid-state spectroscopy and crystallography
- Mechanisms of cancer metastasis
- Hormonal Regulation and Hypertension
- Atomic and Subatomic Physics Research
- Synthesis of heterocyclic compounds
- Nanoplatforms for cancer theranostics
- RNA modifications and cancer
- Biochemical effects in animals
- Synthesis and Catalytic Reactions
- Diet, Metabolism, and Disease
- Antioxidant Activity and Oxidative Stress
- Synthesis and biological activity
- Fibroblast Growth Factor Research
- Lung Cancer Research Studies
- NMR spectroscopy and applications
- Inflammatory mediators and NSAID effects
- Chemical Reaction Mechanisms
Albert Einstein College of Medicine
2023-2025
Case Western Reserve University
2016-2025
Memorial Sloan Kettering Cancer Center
2016-2024
Kettering University
2020
University of Tehran
2007
Tehran University of Medical Sciences
2007
A hallmark of metastasis is the adaptation tumor cells to new environments. Metabolic constraints imposed by serine and glycine-limited brain environment restrict metastatic growth. How metastases overcome these growth-prohibitive conditions poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes rate-limiting step glucose-derived synthesis, a major determinant in multiple human cancer types preclinical models. Enhanced synthesis proved...
Hyperpolarized micro-NMR nondestructively analyzes metabolic activities in scant cells.
DNPH1 is responsible for eliminating the epigenetically modified nucleotide, 5-hydroxymethyl-2′-deoxyuridine 5′-monophosphate (hmdUMP), preventing formation of hmdUTP, a mutation-inducing nucleotide. Loss activity sensitizes PARP inhibition-resistant BRCA-deficient cancers by causing incorporation hmdUTP into DNA. Hydrolysis hmdUMP proceeds through covalent intermediate between Glu104 and 2-deoxyribose 5-phosphate, followed hydrolysis, reaction cycle with two transition states. We describe...
Lipid peroxidation is a complex biochemical process associated with oxidative stress, and its products play crucial roles in cellular signaling the pathophysiology of many diseases. Among diverse array lipid (LPO) products, epoxyketooctadecenoic acids (EKODEs) have emerged as intriguing molecules potential impacts on inflammatory EKODEs arise from linoleic acid reacting reactive oxygen nitrogen species present during inflammation. A hallmark LPO an electrophilic chemical functionality that...
The ability to break down fructose is dependent on ketohexokinase (KHK) that phosphorylates fructose-1-phosphate (F1P). We show KHK expression tightly controlled and limited a small number of organs down-regulated in liver intestinal cancer cells. Loss metabolism also apparent hepatocellular adenoma carcinoma (HCC) patient samples. overexpression cells results decreased flux through glycolysis. then developed strategy detect this metabolic switch vivo using hyperpolarized magnetic resonance...
Glutamine is consumed by rapidly proliferating cells and can provide the carbon nitrogen required for growth through various metabolic pathways. However, delineating fate of glutamine challenging to interrogate in vivo. Hyperpolarized magnetic resonance, providing high transient nuclear resonance signals, provides an approach measure fast biochemical processes Aminohydrolysis at carbon-5 plays important role multiple Here, we a synthetic strategy isotope-enriched forms that prolongs...
The ever-changing tumor microenvironment constantly challenges individual cancer cells to balance supply and demand, presenting vulnerabilities therapeutic opportunities. Everolimus temsirolimus are inhibitors of mTOR (mTORi) approved for treating metastatic renal cell carcinoma (mRCC). However, treatment outcome varies greatly among patients. Accordingly, administration mTORi in mRCC is diminishing, which could potentially result missing timely delivery effective select Here, we implemented...
Abstract Hyperpolarized magnetic resonance spectroscopy (HP MRS) using dynamic nuclear polarization (DNP) is a technique that has greatly enhanced the sensitivity of detecting 13 C nuclei. However, HP MRS decays in liquid state according to spin-lattice relaxation time (T 1 ) nucleus. Sampling signal also destroys polarization, resulting limited temporal ability observe biologically interesting reactions. In this study, we demonstrate sampling hyperpolarized signals permanent magnet at Tesla...
Alterations in arginase enzyme expression are linked with various diseases and have been shown to support disease progression, thus motivating the development of an imaging probe for this enzymatic target. 13C-enriched arginine can be used as a hyperpolarized (HP) magnetic resonance (MR) flux since carbon-6 (157 ppm) is converted urea (163 following arginase-catalyzed hydrolysis. However, scalar relaxation from adjacent 14N-nuclei shortens cabon-6 T1 T2 times, yielding poor spectral...
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now advanced clinical trials, and this study investigates the effect of MK2206, a non-ATP-competitive inhibitor, on cellular metabolism cancer cells. We observed reduction cell motility aerobic glycolysis cells with treatment. These changes were not accompanied by ratio high-energy phosphates or change total protein levels enzymes transporters involved glycolysis. However, decreased NAD
Hyperpolarized [1-13 C] pyruvate can be used to examine the metabolic state of cancer cells, highlighting a key characteristic cancer: upregulated flux lactate, even in presence oxygen (Warburg effect). Thus, rate constant 13 C exchange kPL , serve as biomarker presence, aggressiveness and therapy response. Established vitro hyperpolarized experiments dissolve probe for each cell sample independently, an inefficient process that consumes excessive time resources. Expanding on our previous...
Abstract magnified image Palladium‐catalyzed coupling reaction was found effective for rapid access to pharmacologically interesting 3,4‐diarylisoxazoles derivatives as selective COX‐2 inhibitors. Thus, the between 5‐alkylthio‐3‐aryl‐4‐iodoisoxazoles and arylboronic acids afforded target 5‐alkylthio‐3,4‐diarylisoxazoles in good yields.
Purpose To generate dynamic, volumetric maps of hyperpolarized [1‐ 13 C]pyruvate and its metabolic products in vivo. Methods Maps chemical species were generated with iterative least squares (IDEAL) reconstruction from multiecho echo‐planar imaging (EPI) phantoms thermally polarized C‐labeled chemicals mice injected on a preclinical 3T scanner. The quality the IDEAL decomposition single‐shot multishot phantom images was evaluated using quantitative results simple pulse‐and‐acquire sequence...
Unsymmetric α,β-unsaturated epoxy ketones were synthesized from a bifunctional sulfonium/phosphonium ylide.
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access Abstract, please click on HTML or PDF.
Abstract A hallmark of metastasis is the adaptation tumor cells to new environments. Although it well established that metabolic milieu brain severely deprived nutrients, particularly amino acids serine and its catabolite glycine, how metastases rewire their metabolism survive in nutrient-limited environment poorly understood. Here we demonstrate cell-intrinsic de novo synthesis a major determinant metastasis. Whole proteome comparison triple-negative breast cancer (TNBC) differ capacity...
Abstract The metabolic milieu of the brain is severely deprived nutrients, including amino acids serine and its catabolite glycine. rewiring required for tumor cells to survive in nutrient-limited environment vulnerabilities this confers are poorly understood. Here we demonstrate that cell-intrinsic de novo synthesis a major determinant triple-negative breast cancer (TNBC) metastasis. Whole proteome comparison TNBC differ their capacity colonize reveals 3-phosphoglycerate dehydrogenase...
<p>Time-lapse images of spheroid formation. LnCAP cells were grown on a 1:1 mixture sodium alginate and matrigel in ultra-low adhesion 96-well plates. Time-lapse acquired using 10X objective the Incucyte cell imager platform located humidified culture chamber. Scale bar = 1mm</p>
<p>Hyperpolarized MRS of sodium alginate thread cultures. (A) Bright-field image an in culture and (B) H&E stain the same (C) another cross-section stained with Ki-67. (D) Representative images cultured a rotating plate over period 4 days Ki67 All scale bars represent 500 μm. (E) Thread cultures wound on custom-printed 3D insert, directly deposited into 5mm NMR tube metabolizes hyperpolarized [1-13C] pyruvate to lactate after injection 1mM (F). Quantification integrals hydrate...
<div>Abstract<p>The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now advanced clinical trials, and this study investigates the effect of MK2206, a non–ATP-competitive inhibitor, on cellular metabolism cancer cells. We observed reduction cell motility aerobic glycolysis cells with treatment. These changes were not accompanied by ratio high-energy phosphates or change total protein levels enzymes transporters involved...