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Walter bodmer

Rodolphe Marie, Marie Pødenphant, Kamila Koprowska, Loic Bærlocher, Roland C M Vulders, Jennifer Wilding, Neil Ashley, Simon J McGowan, Dianne van Strijp, Freek van Hemert, Tom Olesen, Niels Agersnap, Brian Bilenberg, Celine Sabatel, Julien Schira, Anders Kristensen, Walter Bodmer, Pieter J van der Zaag, Kalim U Mir
Sequencing the genomes of individual cells enables the direct determination of genetic heterogeneity amongst cells within a population. We have developed an injection-moulded valveless microfluidic device in which single cells from colorectal cancer derived cell lines (LS174T, LS180 and RKO) and fresh colorectal tumors have been individually trapped, their genomes extracted and prepared for sequencing using multiple displacement amplification (MDA). Ninety nine percent of the DNA sequences obtained mapped to a reference human genome, indicating that there was effectively no contamination of these samples from non-human sources...
June 6, 2018: Lab on a Chip
Edmund Gilbert, Seamus O'Reilly, Michael Merrigan, Darren McGettigan, Anne M Molloy, Lawrence C Brody, Walter Bodmer, Katarzyna Hutnik, Sean Ennis, Daniel J Lawson, James F Wilson, Gianpiero L Cavalleri
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
May 3, 2018: Scientific Reports
Daniel J M Crouch, Bruce Winney, Willem P Koppen, William J Christmas, Katarzyna Hutnik, Tammy Day, Devendra Meena, Abdelhamid Boumertit, Pirro Hysi, Ayrun Nessa, Tim D Spector, Josef Kittler, Walter F Bodmer
To discover specific variants with relatively large effects on the human face, we have devised an approach to identifying facial features with high heritability. This is based on using twin data to estimate the additive genetic value of each point on a face, as provided by a 3D camera system. In addition, we have used the ethnic difference between East Asian and European faces as a further source of face genetic variation. We use principal components (PCs) analysis to provide a fine definition of the surface features of human faces around the eyes and of the profile, and chose upper and lower 10% extremes of the most heritable PCs for looking for genetic associations...
January 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Edmund Gilbert, Seamus O'Reilly, Michael Merrigan, Darren McGettigan, Anne M Molloy, Lawrence C Brody, Walter Bodmer, Katarzyna Hutnik, Sean Ennis, Daniel J Lawson, James F Wilson, Gianpiero L Cavalleri
The extent of population structure within Ireland is largely unknown, as is the impact of historical migrations. Here we illustrate fine-scale genetic structure across Ireland that follows geographic boundaries and present evidence of admixture events into Ireland. Utilising the 'Irish DNA Atlas', a cohort (n = 194) of Irish individuals with four generations of ancestry linked to specific regions in Ireland, in combination with 2,039 individuals from the Peoples of the British Isles dataset, we show that the Irish population can be divided in 10 distinct geographically stratified genetic clusters; seven of 'Gaelic' Irish ancestry, and three of shared Irish-British ancestry...
December 8, 2017: Scientific Reports
Marcel Adler, Sandra Ivic, Nicolas S Bodmer, Hugo Ten Cate, Lucas M Bachmann, Walter A Wuillemin, Michael Nagler
BACKGROUND: Studies investigating thromboelastometry or thrombelastography analyses in a physiological context are scattered and not easy to access. OBJECTIVE: To systematically retrieve and describe published reports studying healthy subjects and targeting at the correlation of ROTEM® and TEG® measurements with conventional parameters of hemostasis. METHODS: Systematic Review: Papers were searched in Medline, Scopus and the Science Citation Index database...
April 2017: Transfusion Medicine and Hemotherapy
Daniel Walter Zumofen, Tommaso Guffi, Christian Epple, Birgit Westermann, Anna-Katharina Krähenbühl, Susanne Zabka, Ethan Taub, Daniel Bodmer, Luigi Mariani
BACKGROUND: The goals of treating Koos grade IV vestibular schwannomas are to relieve brainstem compression, preserve or restore neurological function, and achieve long-term tumor control while minimizing tumor- and treatment-related morbidity. OBJECTIVE: To propose a treatment paradigm involving the intentional near-total removal of Koos grade IV vestibular schwannomas, in which a small amount of residual tumor is not dissected off the cisternal portion of the facial nerve...
February 1, 2018: Neurosurgery
Alzbeta Hulikova, Nicholas Black, Lin-Ting Hsia, Jennifer Wilding, Walter F Bodmer, Pawel Swietach
Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly perfused extracellular space. Here, we studied acid handling by myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad), and colorectal cancer (CRC) cells (HCT116, HT29) grown in monoculture or coculture...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Walter F Bodmer
No abstract text is available yet for this article.
May 2016: HLA
Lin-Ting Hsia, Neil Ashley, Djamila Ouaret, Lai Mun Wang, Jennifer Wilding, Walter F Bodmer
Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumor progression. Myofibroblasts previously have been distinguished from normal fibroblasts mostly by the expression of α smooth muscle actin (αSMA). We now have identified AOC3 (amine oxidase, copper containing 3), a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast-reacting mAb PR2D3. The normal and tumor tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts...
April 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
Marina Bacac, Tanja Fauti, Johannes Sam, Sara Colombetti, Tina Weinzierl, Djamila Ouaret, Walter Bodmer, Steffi Lehmann, Thomas Hofer, Ralf J Hosse, Ekkehard Moessner, Oliver Ast, Peter Bruenker, Sandra Grau-Richards, Teilo Schaller, Annette Seidl, Christian Gerdes, Mario Perro, Valeria Nicolini, Nathalie Steinhoff, Sherri Dudal, Sebastian Neumann, Thomas von Hirschheydt, Christiane Jaeger, Jose Saro, Vaios Karanikas, Christian Klein, Pablo Umaña
PURPOSE: CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcγRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB. EXPERIMENTAL DESIGN: CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells...
July 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Marie Pødenphant, Neil Ashley, Kamila Koprowska, Kalim U Mir, Maksim Zalkovskij, Brian Bilenberg, Walter Bodmer, Anders Kristensen, Rodolphe Marie
In this paper, the microfluidic size-separation technique pinched flow fractionation (PFF) is used to separate cancer cells from white blood cells (WBCs). The cells are separated at efficiencies above 90% for both cell types. Circulating tumor cells (CTCs) are found in the blood of cancer patients and can form new tumors. CTCs are rare cells in blood, but they are important for the understanding of metastasis. There is therefore a high interest in developing a method for the enrichment of CTCs from blood samples, which also enables further analysis of the separated cells...
December 21, 2015: Lab on a Chip
Walter Bodmer
In this overview of my research, I have aimed to give the background as to how I came to be involved in my various areas of interest, with an emphasis on the early phases of my career, which largely determined my future directions. I had the enormous good fortune to have worked under two of the most outstanding scientists of the twentieth century, R.A. Fisher and Joshua Lederberg. From mathematics and statistics, I went to population genetics and the early use of computers for modeling and simulation. Molecular biology took me into the laboratory and eventually to somatic cell genetics and human gene mapping...
2015: Annual Review of Genomics and Human Genetics
Stephen Leslie, Bruce Winney, Garrett Hellenthal, Dan Davison, Abdelhamid Boumertit, Tammy Day, Katarzyna Hutnik, Ellen C Royrvik, Barry Cunliffe, Daniel J Lawson, Daniel Falush, Colin Freeman, Matti Pirinen, Simon Myers, Mark Robinson, Peter Donnelly, Walter Bodmer
Fine-scale genetic variation between human populations is interesting as a signature of historical demographic events and because of its potential for confounding disease studies. We use haplotype-based statistical methods to analyse genome-wide single nucleotide polymorphism (SNP) data from a carefully chosen geographically diverse sample of 2,039 individuals from the United Kingdom. This reveals a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography...
March 19, 2015: Nature
Matthew F Jones, Toshifumi Hara, Princy Francis, Xiao Ling Li, Sven Bilke, Yuelin Zhu, Marbin Pineda, Murugan Subramanian, Walter F Bodmer, Ashish Lal
The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of differentiation in the normal colon and in colorectal cancer (CRC). CDX1 activates the expression of enterocyte genes, but it is not clear how the concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are important mediators of gene repression and have been implicated in tumor suppression and carcinogenesis, but the roles of miRNAs in differentiation, particularly in CRC, remain poorly understood. Here, we identified microRNA-215 (miR-215) as a direct transcriptional target of CDX1 by using high-throughput small RNA sequencing to profile miRNA expression in two pairs of CRC cell lines: CDX1-low HCT116 and HCT116 with stable CDX1 overexpression, and CDX1-high LS174T and LS174T with stable CDX1 knockdown...
March 31, 2015: Proceedings of the National Academy of Sciences of the United States of America
Walter Bodmer
From 1900, when Landsteiner first described the ABO blood groups, to the present, the methods used to characterize the genetics of human populations have undergone a remarkable development. Concomitantly, our understanding of the history and spread of human populations across the earth has become much more detailed. As has often been said, a better understanding of the genetic relationships among the peoples of the world is one of the best antidotes to racial prejudices. Such an understanding provides us with a fascinating, improved insight into our origins as well as with valuable information about population differences that are of medical relevance...
February 2015: Genetics
J Bodmer, W Bodmer
It is twenty years and nine workshops on from the first international gathering of tissue typers in Durham, North Carolina. The size and range of the series of meetings centred on this year's workshop show the success achieved by the unique collaboration of workers in the HLA field. The main workshop meeting in Munich, organized by Ekkehard Albert and Wolfgang Mayr, was preceded by the third H-2 and HLA cloning meeting, organized by Jean Dausset in Strasbourg and by a biochemistry workshop in Munich organized by Julia and Walter Bodmer and Michael Crumpton...
September 1984: Immunology Today
Shan Gao, Ilirjana Bajrami, Clare Verrill, Asha Kigozi, Djamila Ouaret, Tamara Aleksic, Ruth Asher, Cheng Han, Paul Allen, Deborah Bailey, Stephan Feller, Takeshi Kashima, Nicholas Athanasou, Jean-Yves Blay, Sandra Schmitz, Jean-Pascal Machiels, Nav Upile, Terry M Jones, George Thalmann, Shazad Q Ashraf, Jennifer L Wilding, Walter F Bodmer, Mark R Middleton, Alan Ashworth, Christopher J Lord, Valentine M Macaulay
Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression...
October 15, 2014: Cancer Research
Neil Ashley, Matthew Jones, Djamila Ouaret, Jenny Wilding, Walter F Bodmer
We have developed a simple procedure for deriving pure cultures of growing cancer cells from colorectal cancers, including material refrigerated overnight, for pathological characterization and cytotoxicity assays. Forty-six cancers were processed and cultures set up under varying culture conditions. Use of a Rho kinase (ROCK1) inhibitor markedly increased culture survival, resulting in 80% of samples growing in culture for at least 1 month and beyond. Overnight refrigeration of samples before culture initiation had little effect on success rates, paving the way for cultures to be established for samples collected over wide geographical areas, such as those for clinical trials...
September 2014: Journal of Pathology
Dmitri Mouradov, Clare Sloggett, Robert N Jorissen, Christopher G Love, Shan Li, Antony W Burgess, Diego Arango, Robert L Strausberg, Daniel Buchanan, Samuel Wormald, Liam O'Connor, Jennifer L Wilding, David Bicknell, Ian P M Tomlinson, Walter F Bodmer, John M Mariadason, Oliver M Sieber
Human colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, to what extent these established cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 colorectal cancer cell lines for mutations and DNA copy number by whole-exome sequencing and SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published for primary colorectal cancers in The Cancer Genome Atlas...
June 15, 2014: Cancer Research
Jennifer L Wilding, Walter F Bodmer
Despite the millions of dollars spent on target validation and drug optimization in preclinical models, most therapies still fail in phase III clinical trials. Our current model systems, or the way we interpret data from them, clearly do not have sufficient clinical predictive power. Current opinion suggests that this is because the cell lines and xenografts that are commonly used are inadequate models that do not effectively mimic and predict human responses. This has become such a widespread belief that it approaches dogma in the field of drug discovery and optimization and has spurred a surge in studies devoted to the development of more sophisticated animal models such as orthotopic patient-derived xenografts in an attempt to obtain more accurate estimates of whether particular cancers will respond to given treatments...
May 1, 2014: Cancer Research
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