A5022922541- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Biochemical and Molecular Research
- Melanoma and MAPK Pathways
- Colorectal Cancer Treatments and Studies
- Synthesis and biological activity
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Cancer Mechanisms and Therapy
- Microfluidic and Capillary Electrophoresis Applications
- Lipid metabolism and biosynthesis
- Cellular transport and secretion
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Microfluidic and Bio-sensing Technologies
- Ubiquitin and proteasome pathways
- Galectins and Cancer Biology
- Mechanical Circulatory Support Devices
- Neonatal Respiratory Health Research
- Pancreatic and Hepatic Oncology Research
- interferon and immune responses
- Innovative Microfluidic and Catalytic Techniques Innovation
- Electrohydrodynamics and Fluid Dynamics
- Sphingolipid Metabolism and Signaling
Pfizer (United States)
2023-2024
Array BioPharma (United States)
2007-2023
Bio-Rad (Canada)
2021
Tsinghua University
2021
McMaster University
2011-2016
National Jewish Health
2000-2013
University of Colorado Denver
2000-2013
University of Florida
2003
The University of Texas at Austin
1998
Rutgers, The State University of New Jersey
1992-1997
Larotrectinib, a selective TRK tyrosine kinase inhibitor (TKI), has demonstrated histology-agnostic efficacy in patients with fusion-positive cancers. Although responses to inhibition can be dramatic and durable, duration of response may eventually limited by acquired resistance. LOXO-195 is TKI designed overcome resistance mediated recurrent domain (solvent front xDFG) mutations identified multiple who have developed TKIs. Activity against these was confirmed enzyme cell-based assays vivo...
AKT1 (NP_005154.2) is a member of the serine/threonine AGC protein kinase family involved in cellular metabolism, growth, proliferation and survival. The three human AKT isozymes are highly homologous multi-domain proteins with both overlapping distinct functions. Dysregulation pathway has been identified multiple cancers. Several clinical trials progress to test efficacy inhibitors treating cancer. Recently, series isozyme-selective allosteric have reported. They require presence...
The protein serine-threonine kinase Akt undergoes a substantial conformational change upon activation, which is induced by the phosphorylation of two critical regulatory residues, threonine 308 and serine 473. Paradoxically, treating cells with adenosine 5'-triphosphate (ATP)-competitive inhibitors results in increased both residues. We show that binding ATP-competitive stabilized conformation phosphorylated sites were inaccessible to phosphatases. ATP also produced this protection sites,...
The protein kinase v-akt murine thymoma viral oncogene homolog (AKT), a key regulator of cell survival and proliferation, is frequently hyperactivated in human cancers. Intramolecular pleckstrin homology (PH) domain–kinase domain (KD) interactions are important maintaining AKT an inactive state. activation proceeds after conformational change that dislodges the PH from KD. To understand these autoinhibitory interactions, we generated mutations at PH–KD interface found most them lead to...
The established pathways from serine to ethanolamine are indirect and involve decarboxylation of phosphatidylserine. Here we show that plants can decarboxylate directly. Using a radioassay based on (Etn) formation, pyridoxal 5′-phosphate-dependent l-serine decarboxylase (SDC) activity was readily detected in soluble extracts leaves diverse species, including spinach,<i>Arabidopsis,</i> rapeseed. A putative<i>Arabidopsis</i> SDC cDNA identified by searching GenBank<sup>TM</sup> for sequences...
The regulation of lipid biosynthesis in the yeast Saccharomyces cerevisiae by fumonisin B1 was examined. Fumonisin inhibited growth cells. Cells supplemented with accumulated free sphinganine and phytosphingosine a dose-dependent manner. cellular concentration ceramide reduced B1-supplemented Ceramide synthase activity found cell membranes B1. synthesis inositol-containing sphingo-lipids inositol phosphorylceramide, mannosylinositol mannosyldiinositol phosphorylceramide. also caused decrease...
The regulation of Saccharomyces cerevisiae membrane-associated phosphatidate phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) activity by sphingoid bases was examined using Triton X-100/lipid-mixed micelles. Sphingosine, phytosphingosine, and sphinganine inhibited purified preparations the 104- 45-kDa forms in a dose-dependent manner. structural requirements for base inhibition were free amino group long chain hydrocarbon. A detailed kinetic analysis performed to determine...
We provided genetic and biochemical evidence that supported the conclusion product of pgpB gene Escherichia coli exhibited diacylglycerol pyrophosphate (DGPP) phosphatase activity. DGPP activity was absent in mutant cells expressed at high levels carrying wild-type on a runaway replication plasmid. The has been primarily characterized by defect phosphatidate (PA) also exhibits defects lyso-PA phosphatidylglycerophosphate activities. defective PA shown to be Mg2+-independent enzyme. membranes...
The V600E mutation of B-Raf kinase results in constitutive activation the MAPK signaling pathway and is present approximately 7% all cancers. Using structure-based design, a novel series pyrazolopyridine inhibitors B-RafV600E was developed. Optimization led to identification 3-methoxy pyrazolopyridines 17 19, potent, selective, orally bioavailable agents that inhibited tumor growth mouse xenograft model driven by with no effect on body weight. On basis their vivo efficacy preliminary safety...
This paper reports the development of microfluidic oxygenator (MFO) units designed for a lung assist device (LAD) newborn infants. will be connected to umbilical vessels like natural placenta and provide gas exchange. The extracorporeal blood flow is only driven by pressure difference between artery vein without use external pumps. LAD in ambient air (∼21% 760 mmHg). main focus this presentation MFO testing various membrane materials with human enhance exchange design fluidic inlets lower...
Protein adsorption on PDMS surfaces poses a significant challenge in microfluidic devices that come into contact with biofluids such as blood. Polyurethane (PU) is often used for the construction of medical devices, but despite having several attractive properties biointerfacing, it has not been widely devices. In this work we developed two new fabrication processes making thin, transparent and flexible PU-based Methods bonding microchannels, integration fluidic interconnections surface...
Abstract A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save lives of newborns with respiratory insufficiency. Recently we presented concept integrated modular lung assist ( LAD ) consists stacked microfluidic single units SOU s) and demonstrated technical details operation prototypes. In this article, present a prototype designed accommodate different needs term preterm infants by permitting changing...
RAF inhibitors have transformed treatment for patients with BRAFV600-mutant cancers, but clinical benefit is limited by adaptive induction of ERK signaling, genetic alterations that induce BRAFV600 dimerization, and poor brain penetration. Next-generation pan-RAF dimer are a narrow therapeutic index. PF-07799933 (ARRY-440) brain-penetrant, selective, pan-mutant BRAF inhibitor. inhibited signaling in vitro, disrupted endogenous mutant-BRAF:wild-type-CRAF dimers, spared wild-type signaling. ±...
A new yeast strain, designated pstB2, that is defective in the conversion of nascent phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn) by PtdSer decarboxylase 2, has been isolated. The pstB2 strain requires ethanolamine for growth. Incubation cells with [(3)H]serine followed analysis aminoglycerophospholipids demonstrates a 50% increase labeling and 72% decrease PtdEtn formation mutant relative parental strain. PSTB2 gene was isolated complementation, it restores prototrophy...
Regulation of Saccharomyces cerevisiae membrane-associated phosphatidate phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) activity by nucleotides was examined using pure enzyme and Triton X-lOO/ phosphatidate-mixed micelles.Adenosine, guanosine, cytidine, uridine inhibited in a dose-dependent manner.ATP CTP were the most potent inhibitors enzyme.A kinetic analysis performed to determine mechanism inhibition nucleotides.The ATP with respect (the substrate) complex.The dependence...
Regulation of Saccharomyces cerevisiae membrane-associated phosphatidate phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) activity by phospholipids was examined using purified enzyme and Triton X-100/phospholipid-mixed micelles. Anionic activated whereas zwitterionic had a slight inhibitory effect on activity. Cardiolipin (A0.5 = 1.9 mol %), CDP-diacylglycerol 2.6 phosphatidylinositol 5.5 %) were the most potent anionic phospholipid activators. Enzyme activation cardiolipin...
Phosphatidylserine (PtdSer) is transported from its site of synthesis in the endoplasmic retiuculum to locus PtdSer decarboxylase 2 (Psd2p) Golgi/vacuole and decarboxylated form phosphatidylethanolamine. Recent biochemical genetic evidence has implicated C2 domain Psd2p a membrane-bound phosphatidylinositol binding/transfer protein, PstB2p, as essential for this transport process. We devised reconstituted system which chemically defined donor membranes function transfer biological acceptor...
Saccharomyces cerevisiae uses multiple biosynthetic pathways for the synthesis of phosphatidylethanolamine. One route involves phosphatidylserine (PtdSer) in endoplasmic reticulum (ER), transport this lipid to endosomes, and decarboxylation by PtdSer decarboxylase 2 (Psd2p) produce Several proteins protein motifs are known be required occur, namely Sec14p homolog PstB2p/Pdr17p; a PtdIns 4-kinase, Stt4p; C2 domain Psd2p. The focus work is on defining protein-protein protein-lipid interactions...