LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Zurück zur letzten Suche Suchhistorie
Erweiterte Suche

Ihre letzten Suchen

  1. AU="Kevin M Haigis"
  2. AU="Brühl, Marius"
  3. AU="Hawash, Mohammed"
  4. AU="Kalra, Sarathi"
  5. AU=Schwab Frank
  6. AU="Tzung-Chi Huang"
  7. AU="Nisa, Maherun"
  8. AU="Resnick, Adam C"
  9. AU="Thomas, Brodie"
  10. AU="Yaming Wang"
  11. AU="Lee, Chun‐Tsu"
  12. AU="Albert Gargallo‐Garriga"
  13. AU="Serwin, Natalia Maria"
  14. AU="La Rosa, Stefano"
  15. AU="Yin-Yin Xie"
  16. AU=White David P
  17. AU="Maria Teresa Viadero"
  18. AU="Wingeter, Márcia A"
  19. AU="Stein, Joshua D"
  20. AU="De Vecchis, Liana"
  21. AU="Chapman, Janet"
  22. AU="Umlai, Umm-Kulthum Ismail"
  23. AU="Reddi, Jyoti M"
  24. AU=Zeissig Sebastian
  25. AU="Valentini, Mariaconsuelo"

Suchergebnis

Treffer 1 - 10 von insgesamt 10

Suchoptionen

  1. Artikel ; Online: The origins and genetic interactions of KRAS mutations are allele- and tissue-specific

    Joshua H. Cook / Giorgio E. M. Melloni / Doga C. Gulhan / Peter J. Park / Kevin M. Haigis

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Band 14

    Abstract: The KRAS gene is often mutated at several hotspot codons in cancer, resulting in similar, yet distinct, functional impacts on the KRAS protein. Here, the authors examine the genetic interactions of the different KRAS mutations across multiple cancer ... ...

    Abstract The KRAS gene is often mutated at several hotspot codons in cancer, resulting in similar, yet distinct, functional impacts on the KRAS protein. Here, the authors examine the genetic interactions of the different KRAS mutations across multiple cancer types and discover that KRAS mutations have allele- and tissue-specific mutagenic origins, comutation patterns, and dependency interactions.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-03-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  2. Artikel ; Online: Computational translation of genomic responses from experimental model systems to humans.

    Douglas K Brubaker / Elizabeth A Proctor / Kevin M Haigis / Douglas A Lauffenburger

    PLoS Computational Biology, Vol 15, Iss 1, p e

    2019  Band 1006286

    Abstract: The high failure rate of therapeutics showing promise in mouse models to translate to patients is a pressing challenge in biomedical science. Though retrospective studies have examined the fidelity of mouse models to their respective human conditions, ... ...

    Abstract The high failure rate of therapeutics showing promise in mouse models to translate to patients is a pressing challenge in biomedical science. Though retrospective studies have examined the fidelity of mouse models to their respective human conditions, approaches for prospective translation of insights from mouse models to patients remain relatively unexplored. Here, we develop a semi-supervised learning approach for inference of disease-associated human differentially expressed genes and pathways from mouse model experiments. We examined 36 transcriptomic case studies where comparable phenotypes were available for mouse and human inflammatory diseases and assessed multiple computational approaches for inferring human biology from mouse datasets. We found that semi-supervised training of a neural network identified significantly more true human biological associations than interpreting mouse experiments directly. Evaluating the experimental design of mouse experiments where our model was most successful revealed principles of experimental design that may improve translational performance. Our study shows that when prospectively evaluating biological associations in mouse studies, semi-supervised learning approaches, combining mouse and human data for biological inference, provide the most accurate assessment of human in vivo disease processes. Finally, we proffer a delineation of four categories of model system-to-human "Translation Problems" defined by the resolution and coverage of the datasets available for molecular insight translation and suggest that the task of translating insights from model systems to human disease contexts may be better accomplished by a combination of translation-minded experimental design and computational approaches.
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 006
    Sprache Englisch
    Erscheinungsdatum 2019-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  3. Artikel ; Online: Cross-species transcriptomic signatures predict response to MK2 inhibition in mouse models of chronic inflammation

    Lucia Suarez-Lopez / Bing Shui / Douglas K. Brubaker / Marza Hill / Alexander Bergendorf / Paul S. Changelian / Aisha Laguna / Alina Starchenko / Douglas A. Lauffenburger / Kevin M. Haigis

    iScience, Vol 24, Iss 12, Pp 103406- (2021)

    2021  

    Abstract: Summary: Inflammatory bowel diseases (IBDs) are genetically complex and exhibit significant inter-patient heterogeneity in disease presentation and therapeutic response. Here, we show that mouse models of IBD exhibit variable responses to inhibition of ... ...

    Abstract Summary: Inflammatory bowel diseases (IBDs) are genetically complex and exhibit significant inter-patient heterogeneity in disease presentation and therapeutic response. Here, we show that mouse models of IBD exhibit variable responses to inhibition of MK2, a pro-inflammatory serine/threonine kinase, and that MK2 inhibition suppresses inflammation by targeting inflammatory monocytes and neutrophils in murine models. Using a computational approach (TransComp-R) that allows for cross-species comparison of transcriptomic features, we identified an IBD patient subgroup that is predicted to respond to MK2 inhibition, and an independent preclinical model of chronic intestinal inflammation predicted to be non-responsive, which we validated experimentally. Thus, cross-species mouse-human translation approaches can help to identify patient subpopulations in which to deploy new therapies.
    Schlagwörter Immunology ; Computational bioinformatics ; Systems biology ; Transcriptomics ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  4. Artikel ; Online: A Role for Mitochondrial Translation in Promotion of Viability in K-Ras Mutant Cells

    Timothy D. Martin / Danielle R. Cook / Mei Yuk Choi / Mamie Z. Li / Kevin M. Haigis / Stephen J. Elledge

    Cell Reports, Vol 20, Iss 2, Pp 427-

    2017  Band 438

    Abstract: Activating mutations in the KRAS oncogene are highly prevalent in tumors, especially those of the colon, lung, and pancreas. To better understand the genetic dependencies that K-Ras mutant cells rely upon for their growth, we employed whole-genome CRISPR ...

    Abstract Activating mutations in the KRAS oncogene are highly prevalent in tumors, especially those of the colon, lung, and pancreas. To better understand the genetic dependencies that K-Ras mutant cells rely upon for their growth, we employed whole-genome CRISPR loss-of-function screens in two isogenic pairs of cell lines. Since loss of essential genes is uniformly toxic in CRISPR-based screens, we also developed a small hairpin RNA (shRNA) library targeting essential genes. These approaches uncovered a large set of proteins whose loss results in the selective reduction of K-Ras mutant cell growth. Pathway analysis revealed that many of these genes function in the mitochondria. For validation, we generated isogenic pairs of cell lines using CRISPR-based genome engineering, which confirmed the dependency of K-Ras mutant cells on these mitochondrial pathways. Finally, we found that mitochondrial inhibitors reduce the growth of K-Ras mutant tumors in vivo, aiding in the advancement of strategies to target K-Ras-driven malignancy.
    Schlagwörter CRISPR ; shRNA ; KRAS ; mitochondria ; synthetic lethal ; genetic screen ; mitoribosome ; oxidative phosphorylation ; mitochondrial translation ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2017-07-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  5. Artikel ; Online: The colonic epithelium plays an active role in promoting colitis by shaping the tissue cytokine profile.

    Jesse Lyons / Phaedra C Ghazi / Alina Starchenko / Alessio Tovaglieri / Katherine R Baldwin / Emily J Poulin / Jessica J Gierut / Casie Genetti / Vijay Yajnik / David T Breault / Douglas A Lauffenburger / Kevin M Haigis

    PLoS Biology, Vol 16, Iss 3, p e

    2018  Band 2002417

    Abstract: Inflammatory bowel disease (IBD) is a chronic condition driven by loss of homeostasis between the mucosal immune system, the commensal gut microbiota, and the intestinal epithelium. Our goal is to understand how these components of the intestinal ... ...

    Abstract Inflammatory bowel disease (IBD) is a chronic condition driven by loss of homeostasis between the mucosal immune system, the commensal gut microbiota, and the intestinal epithelium. Our goal is to understand how these components of the intestinal ecosystem cooperate to control homeostasis. By combining quantitative measures of epithelial hyperplasia and immune infiltration with multivariate analysis of inter- and intracellular signaling, we identified epithelial mammalian target of rapamycin (mTOR) signaling as a potential driver of inflammation in a mouse model of colitis. A kinetic analysis of mTOR inhibition revealed that the pathway regulates epithelial differentiation, which in turn controls the cytokine milieu of the colon. Consistent with our in vivo analysis, we found that cytokine expression of organoids grown ex vivo, in the absence of bacteria and immune cells, was dependent on differentiation state. Our study suggests that proper differentiation of epithelial cells is an important feature of colonic homeostasis because of its effect on the secretion of inflammatory cytokines.
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570 ; 610
    Sprache Englisch
    Erscheinungsdatum 2018-03-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  6. Artikel ; Online: Oncogenic K-Ras promotes proliferation in quiescent intestinal stem cells

    Jessica J. Gierut / Jesse Lyons / Manasvi S. Shah / Casie Genetti / David T. Breault / Kevin M. Haigis

    Stem Cell Research, Vol 15, Iss 1, Pp 165-

    2015  Band 171

    Abstract: K-Ras is a monomeric GTPase that controls cellular and tissue homeostasis. Prior studies demonstrated that mutationally activated K-Ras (K-RasG12D) signals through MEK to promote expansion and hyperproliferation of the highly mitotically active transit- ... ...

    Abstract K-Ras is a monomeric GTPase that controls cellular and tissue homeostasis. Prior studies demonstrated that mutationally activated K-Ras (K-RasG12D) signals through MEK to promote expansion and hyperproliferation of the highly mitotically active transit-amplifying cells (TACs) in the intestinal crypt. Its effect on normally quiescent stem cells was unknown, however. Here, we have used an H2B-Egfp transgenic system to demonstrate that K-RasG12D accelerates the proliferative kinetics of quiescent intestinal stem cells. As in the TAC compartment, the effect of mutant K-Ras on the quiescent stem cell is dependent upon activation of MEK. Mutant K-Ras is also able to increase self-renewal potential of intestinal stem cells following damage. These results demonstrate that mutant K-Ras can influence intestinal homeostasis on multiple levels.
    Schlagwörter Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2015-07-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  7. Artikel ; Online: Comparative analysis of radiosensitizers for K-RAS mutant rectal cancers.

    Laura B Kleiman / Angela M Krebs / Stephen Y Kim / Theodore S Hong / Kevin M Haigis

    PLoS ONE, Vol 8, Iss 12, p e

    2013  Band 82982

    Abstract: Approximately 40% of rectal cancers harbor activating K-RAS mutations, and these mutations are associated with poor clinical response to chemoradiotherapy. We aimed to identify small molecule inhibitors (SMIs) that synergize with ionizing radiation (IR) ( ...

    Abstract Approximately 40% of rectal cancers harbor activating K-RAS mutations, and these mutations are associated with poor clinical response to chemoradiotherapy. We aimed to identify small molecule inhibitors (SMIs) that synergize with ionizing radiation (IR) ("radiosensitizers") that could be incorporated into current treatment strategies for locally advanced rectal cancers (LARCs) expressing mutant K-RAS. We first optimized a high-throughput assay for measuring individual and combined effects of SMIs and IR that produces similar results to the gold standard colony formation assay. Using this screening platform and K-RAS mutant rectal cancer cell lines, we tested SMIs targeting diverse signaling pathways for radiosensitizing activity and then evaluated our top hits in follow-up experiments. The two most potent radiosensitizers were the Chk1/2 inhibitor AZD7762 and the PI3K/mTOR inhibitor BEZ235. The chemotherapeutic agent 5-fluorouracil (5-FU), which is used to treat LARC, synergized with AZD7762 and enhanced radiosensitization by AZD7762. This study is the first to compare different SMIs in combination with IR for the treatment of K-RAS mutant rectal cancer, and our findings suggest that Chk1/2 inhibitors should be evaluated in new clinical trials for LARC.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2013-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  8. Artikel ; Online: Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.

    Ken S Lau / Virna Cortez-Retamozo / Sarah R Philips / Mikael J Pittet / Douglas A Lauffenburger / Kevin M Haigis

    PLoS Biology, Vol 10, Iss 9, p e

    2012  Band 1001393

    Abstract: Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to ... ...

    Abstract Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-α. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-α-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting.
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  9. Artikel ; Online: BAY61-3606 affects the viability of colon cancer cells in a genotype-directed manner.

    Ken S Lau / Tinghu Zhang / Krystle R Kendall / Douglas Lauffenburger / Nathanael S Gray / Kevin M Haigis

    PLoS ONE, Vol 7, Iss 7, p e

    2012  Band 41343

    Abstract: K-RAS mutation poses a particularly difficult problem for cancer therapy. Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K- ... ...

    Abstract K-RAS mutation poses a particularly difficult problem for cancer therapy. Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K-RAS-induced oncogenicity would be of tremendous value.We searched for small molecule kinase inhibitors that preferentially affect the growth of colorectal cancer cells expressing mutant K-RAS. The mechanism of action of one inhibitor was explored using chemical and genetic approaches.We identified BAY61-3606 as an inhibitor of proliferation in colorectal cancer cells expressing mutant forms of K-RAS, but not in isogenic cells expressing wild-type K-RAS. In addition to its anti-proliferative effects in mutant cells, BAY61-3606 exhibited a distinct biological property in wild-type cells in that it conferred sensitivity to inhibition of RAF. In this context, BAY61-3606 acted by inhibiting MAP4K2 (GCK), which normally activates NFκβ signaling in wild-type cells in response to inhibition of RAF. As a result of MAP4K2 inhibition, wild-type cells became sensitive to AZ-628, a RAF inhibitor, when also treated with BAY61-3606.These studies indicate that BAY61-3606 exerts distinct biological activities in different genetic contexts.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  10. Artikel ; Online: Correction

    Ken S. Lau / Virna Cortez-Retamozo / Sarah R. Philips / Mikael J. Pittet / Douglas A. Lauffenburger / Kevin M. Haigis

    PLoS Biology, Vol 10, Iss

    Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium.

    2012  Band 10

    Schlagwörter Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2012-10-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

Zum Seitenanfang