A5078107292- Cancer, Hypoxia, and Metabolism
- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
- Metabolism, Diabetes, and Cancer
- Metalloenzymes and iron-sulfur proteins
- Electrocatalysts for Energy Conversion
- Cancer Research and Treatments
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Immune cells in cancer
- Sirtuins and Resveratrol in Medicine
- Advanced battery technologies research
- Cancer, Lipids, and Metabolism
- Vitamin C and Antioxidants Research
- Microtubule and mitosis dynamics
- Bioactive Compounds and Antitumor Agents
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Extracellular vesicles in disease
- Autophagy in Disease and Therapy
- Cancer therapeutics and mechanisms
- Metabolomics and Mass Spectrometry Studies
- Microbial Natural Products and Biosynthesis
- Virus-based gene therapy research
Cold Spring Harbor Laboratory
2020-2024
Cornell University
2013-2020
University of Oxford
2009-2012
University of California, Davis
2012
University of Nebraska–Lincoln
2009
University of Michigan
2009
University of Dundee
2009
The enterobacterium Escherichia coli synthesizes two H(2) uptake enzymes, Hyd-1 and Hyd-2. We show using precise electrochemical kinetic measurements that the properties of Hyd-2 contrast strikingly, may be individually optimized to function under distinct environmental conditions. is well suited for fast efficient catalysis in more reducing environments, extent vitro it behaves as a bidirectional hydrogenase. In contrast, active oxidation oxidizing conditions cannot reverse. Importantly,...
Abstract Many transformed cells exhibit altered glucose metabolism and increased utilization of glutamine for anabolic bioenergetic processes. These metabolic adaptations, which accompany tumorigenesis, are driven by oncogenic signals. Here we report that the transcription factor c-Jun, product proto-oncogene JUN , is a key regulator mitochondrial glutaminase (GLS) levels. Activation c-Jun downstream Rho GTPase signalling leads to elevated GLS gene expression activity. In human breast cancer...
An important clue to the mechanism for O2 tolerance of certain [NiFe]-hydrogenases is conserved presence a modified environment around iron–sulfur cluster that proximal active site. The O2-tolerant enzymes contain two cysteines, located at opposite ends this cluster, which are glycines in their O2-sensitive counterparts. strong correlation highlights special importance electron-transfer activity protection used combat O2. Site-directed mutagenesis has been carried out on Escherichia coli...
The mitochondrial enzyme glutaminase (GLS) is frequently up-regulated during tumorigenesis and being evaluated as a target for cancer therapy. GLS catalyzes the hydrolysis of glutamine to glutamate, which then supplies diverse metabolic pathways with carbon and/or nitrogen. Here, we report that SIRT5, NAD+-dependent lysine deacylase, plays key role in stabilizing GLS. In transformed cells, SIRT5 regulates metabolism by desuccinylating thereby protecting it from ubiquitin-mediated...
Efforts to target glutamine metabolism for cancer therapy have focused on the glutaminase isozyme GLS. The importance of other isozyme, GLS2, in has remained unclear, and it been described as a tumor suppressor some contexts. Here, we report that GLS2 is upregulated essential luminal-subtype breast tumors, which account >70% incidence. We show expression elevated by GATA3 cells but suppressed promoter methylation basal-subtype cells. Although luminal cancers resist GLS-selective inhibitors,...
"Hyd-1", produced by Escherichia coli, exemplifies a special class of [NiFe]-hydrogenase that can sustain high catalytic H2 oxidation activity in the presence O2—an intruder normally incapacitates sulfur- and electron-rich active site. The mechanism "O2 tolerance" involves critical role for Fe–S clusters electron relay, which is to ensure availability—for immediate transfer back site—of all electrons required reduce an attacking O2 molecule completely harmless H2O. unique [4Fe-3S] cluster...
The Accelerated SuFEx Click Chemistry (ASCC) protocol, adapted to a 96-well plate format, has been applied the late-stage derivatization of bioactive molecules and array synthesis anticancer agents, showcasing its potential for drug discovery.
The water-gas shift (WGS) reaction (CO + H(2)O <==> CO(2) H(2)) is of major industrial significance in the production H(2) from hydrocarbon sources. High temperatures are required, typically excess 200 degrees C, using d-metal catalysts on oxide supports. In our study WGS process separated into two half-cell electrochemical reactions (H(+) reduction and CO oxidation), catalyzed by enzymes attached to a conducting particle. H(+) hydrogenase, Hyd-2, Escherichia coli, oxidation carbon monoxide...
An elevated neutrophil-lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated cachexia, terminal wasting syndrome. Here, using murine model systems colorectal pancreatic we show that neutrophilia in circulation multiple organs, accompanied by extramedullary hematopoiesis, an early event during progression. Transcriptomic metabolic assessment reveals neutrophils tumor-bearing animals utilize aerobic glycolysis, similar to cells. Although pharmacological...
The metabolic microenvironment of tumors is characterized by fluctuating and limited nutrient availability. To survive these conditions, cancer cell-intrinsic mechanisms sense signal nutritional status. We describe how glutaminase (GLS) destabilized lysine succinylation stabilized the NAD+-dependent desuccinylase sirtuin 5 (SIRT5), coupling levels to flux.
We report an improved 4-step semisynthesis of (−)-jerantinine A and (−)-melodinine P from (−)-tabersonine, qualify their potency against TNBC cells confirm they induce oxidative stress. JA also acts as a potent inhibitor nucleotide metabolism.
The dependency of cancer cells on glucose can be targeted with high-fat low-carbohydrate ketogenic diet (KD). However, hepatic ketogenesis is suppressed in IL-6 producing cancers, which prevents the utilization this nutrient source as energy for organism. In two associated murine models cachexia we describe delayed tumor growth but accelerated onset and shortened survival when mice are fed KD. Mechanistically, find uncoupling a consequence biochemical interaction simultaneously occurring...