Wyniki wyszukiwania dla: Scott E. Martin

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artykuł

Multiple-gene targeting and mismatch tolerance can confound analysis of genome-wide pooled CRISPR screens

Jean-Philippe Fortin, Jenille Tan, Karen E. Gascoigne, Peter M. Haverty, więcej

Genome Biology > 2019 > 20 > 1 > 1-25

Background Genome-wide loss-of-function screens using the CRISPR/Cas9 system allow the efficient discovery of cancer cell vulnerabilities. While several studies have focused on correcting for DNA cleavage toxicity biases associated with copy number alterations, the effects of sgRNAs co-targeting multiple genomic loci in CRISPR screens have not been discussed. Results In this work, we analyze CRISPR...

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Coordination between Two Branches of the Unfolded Protein Response Determines Apoptotic Cell Fate

Tsun-Kai Chang, David A. Lawrence, Min Lu, Jenille Tan, więcej

Molecular Cell > 2018 > 71 > 4 > 629-636.e5

The kinases PERK and IRE1 alleviate endoplasmic reticulum (ER) stress by orchestrating the unfolded protein response (UPR). If stress mitigation fails, PERK promotes cell death by activating pro-apoptotic genes, including death receptor 5 (DR5). Conversely, IRE1—which harbors both kinase and endoribonuclease (RNase) modules—blocks apoptosis through regulated IRE1-dependent decay (RIDD) of DR5 mRNA...

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Identification of a novel miRNA that increases transient protein expression in combination with valproic acid

Hermann‐Josef Meyer, Dorothea Reilly, Scott E. Martin, Athena W. Wong

Biotechnology Progress > 33 > 4 > 1139 - 1145

Transient gene expression in mammalian cells is an efficient process to produce recombinant proteins for various research applications and large molecule therapeutics development. For the first time, we report a screen to identify human microRNAs (miRNAs) that increase titers after polyethylenimine (PEI) mediated transient transfection of a HEK293 cell line. From a library of 875 miRNAs, we identified...

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Enhanced Functional Genomic Screening Identifies Novel Mediators of Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons

Derek S. Welsbie, Katherine L. Mitchell, Vinod Jaskula-Ranga, Valentin M. Sluch, więcej

Neuron > 2017 > 94 > 6 > 1142-1154.e6

Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially...

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Functional Genomic Screening Reveals Splicing of the EWS-FLI1 Fusion Transcript as a Vulnerability in Ewing Sarcoma

Patrick J. Grohar, Suntae Kim, Guillermo O. Rangel Rivera, Nirmalya Sen, więcej

Cell Reports > 2016 > 14 > 3 > 598-610

Ewing sarcoma cells depend on the EWS-FLI1 fusion transcription factor for cell survival. Using an assay of EWS-FLI1 activity and genome-wide RNAi screening, we have identified proteins required for the processing of the EWS-FLI1 pre-mRNA. We show that Ewing sarcoma cells harboring a genomic breakpoint that retains exon 8 of EWSR1 require the RNA-binding protein HNRNPH1 to express in-frame EWS-FLI1...

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MiRNA mimic screen for improved expression of functional neurotensin receptor from HEK 293 cells

Su Xiao, Yu‐Chi Chen, Michael J. Betenbaugh, Scott E. Martin, więcej

Biotechnology and Bioengineering > 112 > 8 > 1632 - 1643

Obtaining adequate quantities of functional mammalian membrane proteins has been a bottleneck in their structural and functional studies because the expression of these proteins from mammalian cells is relatively low. To explore the possibility of enhancing expression of these proteins using miRNA, a stable T‐REx‐293 cell line expressing the neurotensin receptor type 1 (NTSR1), a hard‐to‐express G...

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Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity

Oliver Ou, Konrad Huppi, Sirisha Chakka, Kristen Gehlhaus, więcej

Cancer Letters > 2014 > 354 > 2 > 336-347

The use of molecularly targeted drugs as single agents has shown limited utility in many tumor types, largely due to the complex and redundant nature of oncogenic signaling networks. Targeting of the PI3K/AKT/mTOR pathway through inhibition of mTOR in combination with aromatase inhibitors has seen success in particular sub-types of breast cancer and there is a need to identify additional synergistic...

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Evaluating Medical Marijuana Dispensary Policies: Spatial Methods for the Study of Environmentally-Based Interventions

Bridget Freisthler, Nancy J. Kepple, Revel Sims, Scott E. Martin

American Journal of Community Psychology > 2013 > 51 > 1-2 > 278-288

In 1996, California was the first state to pass a Compassionate Use Act allowing for the legal use of marijuana for medical purposes. Here we review several current policy and land use environmental interventions designed to limit problems related to the influx of medical marijuana dispensaries across California cities. Then we discuss the special challenges, solutions, and techniques used for studying...

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High-throughput screening for genes that prevent excess DNA replication in human cells and for molecules that inhibit them

Chrissie Y. Lee, Ronald L. Johnson, Jennifer Wichterman-Kouznetsova, Rajarshi Guha, więcej

Methods > 2012 > 57 > 2 > 234-248

High-throughput screening (HTS) provides a rapid and comprehensive approach to identifying compounds that target specific biological processes as well as genes that are essential to those processes. Here we describe a HTS assay for small molecules that induce either DNA re-replication or endoreduplication (i.e. excess DNA replication) selectively in cells derived from human cancers. Such molecules...

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Inactivation of Escherichia coli cells with sonication, manosonication, thermosonication, and manothermosonication: Microbial responses and kinetics modeling

Hyoungill Lee, Bin Zhou, Wei Liang, Hao Feng, więcej

Journal of Food Engineering > 2009 > 93 > 3 > 354-364

The responses of Escherichia coli K12 to sonication, manosonication (MS), thermosonication (TS), and manothermosonication (MTS) treatments were investigated at 40, 47, 54, and 61°C and 100, 300, 400, and 500kPa, in comparison with heat only treatments at the same temperatures. The inactivation kinetics were evaluated with five selected models and two statistical indices. Within the time frame (4min)...

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Effect of Lactococcus lactis UQ2 and its bacteriocin on Listeria monocytogenes biofilms

Blanca E. García-Almendárez, Issac K.O. Cann, Scott E. Martin, Isabel Guerrero-Legarreta, więcej

Food Control > 2008 > 19 > 7 > 670-680

Listeria monocytogenes is a foodborne pathogen of major concern in food processing due to its wide environmental distribution and ability to form biofilms. Lactococcus lactis UQ2 is a bacteriocinogenic strain isolated from Mexican-style cheese, genetically identified as nisin A. It was grown on supplemented whey medium, representing an alternative, and probably more economical way to obtain this bacteriocin...

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MicroRNAs and genomic instability

Konrad Huppi, Natalia Volfovsky, Mark Mackiewicz, Timothy Runfola, więcej

Seminars in Cancer Biology > 2007 > 17 > 1 > 65-73

A new species of non-coding RNA, microRNAs (miRNAs) has been identified that may regulate the expression of as many as one third to one half of all protein encoding genes. MicroRNAs are found throughout mammalian genomes, but an association between the location of these miRNAs and regions of genomic instability (or fragile sites) in humans has been suggested [1]. In this review we discuss the possible...

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A Synthetic Mimic of Human Fc Receptors: Defined Chemical Modification of Cell Surfaces Enables Efficient Endocytic Uptake of Human Immunoglobulin-G

Siwarutt Boonyarattanakalin, Scott E. Martin, Qi Sun, Blake R. Peterson

Journal of the American Chemical Society > 2006 > 128 > 35 > 11463 - 11470

artykuł

Mismatched siRNAs downregulate mRNAs as a function of target site location

Scott E. Martin, Natasha J. Caplen

FEBS Letters > 2006 > 580 > 15 > 3694-3698

In mammalian cells, RNA interference can be mediated by synthetic duplex RNAs, termed small interfering RNAs (siRNAs), which assist in cleaving completely complementary mRNA transcripts. MicroRNAs (miRNAs) are endogenous small RNAs that assist in translationally repressing mRNAs with regions of partial complementarity, but may also reduce transcript levels. Since miRNAs predominantly interact with...

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Defining and Assaying RNAi in Mammalian Cells

Konrad Huppi, Scott E. Martin, Natasha J. Caplen

Molecular Cell > 2005 > 17 > 1 > 1-10

The investigation of protein function through the inhibition of activity has been critical to our understanding of many normal and abnormal biological processes. Until recently, functional inhibition in biological systems has been induced using a variety of approaches including small molecule antagonists, antibodies, aptamers, ribozymes, antisense oligonucleotides or transcripts, morpholinos, dominant-negative...