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Dear ICBC Team Members:
Happy Holidays and best wishes for a Happy New Year to all! As we are moving closer to 2008, I would like to remind everyone to register for the upcoming meeting in Honolulu, Hawaii, February 20-22, 2008. A link to the registration is provided in this issue.
Once again, ICBC team members have had a busy fall. Two very successful workshops were conducted, a bioinformatics workshop hosted by Dr. Myeong-Hee Yu and Prof. Eunok Paek of the Functional Proteomics Center, and a SISCAPA workshop hosted by Dr. Hyang-Sook Yoo of the Korea Research Institute of Bioscience and Biotechnology. Again, I would like to commend team leaders for organizing these informative workshops.
Also in this issue we have a report from Dr. Martin McIntosh's group, who is working on a number of new developments, and a team highlight on the prostate cancer team led by Dr. William Watson at Dublin Molecular Medicine Centre. The newsletter also contains a link to a list of recent publications by ICBC team members.
Best regards,
Lee Hartwell
President and Director
Fred Hutchinson Cancer Research Center
None at this time.
CPAS updateCPAS is now undergoing a rapid number of new developments, which will be added to the new distribution as it completes. Many of these advancements are funded as part of a large series of development grants from the Canary Foundation. Of most interest to the proteomics community are the developments to improve label-free comparisons, including by both spectral counting and also peptide-intensity (e.g., methods of use by msInspect and other peptide finger-printing approach). Special modules for handling MS peptide intensity data are being added and will be available soon. As CPAS implements the label free comparisons, it will be implemented in a generic framework which will allow the use of many signal processing tools, but will have its first implementation based on msInspect, and perhaps PEPPeR.
Under this same funding mechanism, msInspect has been integrated into the PEPPeR suite of algorithms developed by the Broad institute, which combining MS and MS/MS data. MsInspect is used as the core signal processing component for locating and quantitating peptides. In PEPPeR its own algorithms for aligning MS/MS and MS data and for clustering are used. The more recent version of msInspect, called msInspect/AMT, now includes its own capacity for integrating MS and MS/MS data using generalized Accurate Mass and Time (AMT) tag approach. We are now evaluating the possibility of integrating some of the PEPPeR downstream clustering tools into msInspect.
Overall, over the past months at least ten new laboratories around the world have installed a CPAS installation. Moreover, the platform which CPAS has been built on, now part of the Labkey Software Foundation, now has the capacity for analyzing and managing flow cytometry data.
Other recent additions to CPAS can be found at www.labkey.org/Project/home/begin.view.
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You may access the list of recent publications by Consortium members here.
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None at this time.
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Recent Regional Workshops
Bioinformatics Workshop at Korea University, October 5-6, 2007Dr. Myeong-Hee Yu and Prof. Eunok Paek of the Functional Proteomics Center (KIST) hosted a Bioinformatics Workshop October 5-6, 2007 at Korea University. The workshop had 45 registrants and covered topics such as data analysis & management by CPAS and also using TPP (ISB's Trans Proteomic Pipeline), analysis modules, and FT data analysis (including ICR2LS, SNU, and MMF[Monoisotopic mass filtering]). Guest speakers included Damon May (Hutchinson Center), Josh Tasman and Henry Lam (ISB), Chee-Hong Wong (A*Star), Heejin Park (Hanyang University), and Drs. Gordon Anderson and Richard Smith (PNNL).
SISCAPA workshop at Korea Research Institute of Bioscience and Biotechnology (KRIBB)Dr. Hyang-Sook Yoo of KIST hosted a SISCAPA workshop for approximately 20 scientists from KRIBB and Korea Basic Science Institute (KBSI). Guest speakers were Dr. Terry Pearson and Dr. Christoph Borchers from the University of Victoria, British Columbia, Canada. A summary of the workshop follows.
Identification and validation of cancer biomarkers in the blood of cancer patients in early stage of cancer progression is the key issue in biomarker discovery. Sensitive methods that can detect the quantitative or qualitative changes of the protein markers are crucial for the success of discovering key markers. The recent introduction of stable isotope standards and capture by anti-peptide antibody (SISCAPA) method by Lee Anderson and Terry Pearson et al opens up the new opportunity for validating the markers in a more sensitive way. Since this method is worth trying to apply in biomarker discovery and validation of liver and stomach cancers, the KRIBB team, invited Drs. Terry Pearson and Christoph Borchers to speak on this subject at the SISCAPA workshop.
Dr. Pearson introduced the key points of SISCAPA, the merits of enrichment of the targets by anti-peptide antibody and use of rabbit monoclonal antibodies against peptide antigens. The combination of sensitivity of antibody capturing with specificity of mass-spec detection make this method feasible in detecting femtamole levels of the markers in serum.
Dr. Borchers introduced the use of iMALDI and several ways of using high field FTMS for detecting biomarkers, especially for metabolites. The KRIBB team learned that iMALDI and SISCAPA methods could be applied to lectin affinity enrichment glycoprotein detection in liver and stomach cancers and that the mass spectrometry facilities at the KBSI and University of Victoria could be used for this purpose. Drs. Pearson and Borchers agreed to exchange graduate students and scientists to facilitate establishment of this technology at KRIBB. The KRIBB team, with the help of Drs. Pearson and Borchers, will try to use this method with known targets on which they are working. Clinical validation of the known targets is planned for our collaboration.
Once the KRIBB team is successful with this method, they will have a second workshop to disseminate the method to other ICBC members.ICBC Meetings
The next ICBC meeting will be held February 20 - 22, 2008 in Honolulu, on the island of Oahu, Hawaii. The meeting will take place at the Hyatt Regency Waikiki Resort. A link for the meeting website is included below. Please note: you must register for the meeting via the Registration link on the meeting page, and separately register for your hotel via the Accommodations link.
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| Project Title: | Prostate Cancer Biomarker Discovery; a Program of the Prostate Cancer Research Consortium | |
| Cancer Site(s): | Prostate | |
| Principal Investigator(s): |
William Watson, Ph.D. | |
| Participating Institutions: |
University College Dublin | |
| Mouse Model(s): | PC-3 xenograft (under development) | |
| Technical Approaches: | Fractionation of abundant proteins (Serum and Urine) DIGE SELDI Tissue Microarrays Protein Lysate Arrays Digital Slide Scanning Multiplex Assay Development |
Brief Description of Project:
Current detection strategies for prostate cancer, which shows increased incidence worldwide, are inadequate due to poor specificity. This has lead to significant dilemmas in identifying the correct therapeutic strategy, given that aggressive approaches are associated with a 30-60% risk of treatment-related side effects. We have previously established the Prostate Cancer Research Consortium (PCRC), a Dublin Molecular Medicine Centre (DMMC) flagship program which has built a shared prostate cancer bio-resource, a powerful tool for facilitating multidisciplinary trans-institutional research. The current Prostate Cancer Biomarker Discovery Program provides a focused approach to cancer biomarker discovery, evaluation and validation. This program also permits promising markers from pre-clinical exploratory studies to be evaluated. Using a comprehensive approach, the PCRC Bio-resource is interrogated with a view to identifying novel biomarker candidates. Preliminary work has (i) identified prostate cancer-specific methylation targets, (ii) allowed development of a prostate cancer-specific transcriptome array from the Bio-resource, and (iii) detected a potential proteomic signature of disease grade. The current programme aims to use proteomic approaches to identify common pathways in prostate cancer and validate lead candidates in serum and urine from prostate cancer patients. Validated candidates identified from this multi-step approach will permit guided biopsies to be performed, together with appropriate pathological and molecular analysis, providing accurate diagnostic information to inform appropriate treatment for prostate cancer patients.
Team Members and Expertise:
William WATSON, Ph.D. [william.watson@ucd.ie]
Dr. Watson is a Senior Lecturer in the School of Medicine and Medical Science, University College Dublin (UCD) and Principal Investigator at the UCD Conway Institute and Dublin Molecular Medicine Centre. He is also Lead Co-ordinator of the Cancer Biology Group in the UCD Conway Institute, which consists of 29 independent investigators. He has used transcriptomic and proteomic approaches to investigate the cellular and molecular mechanisms by which prostate cancer epithelial cell die, leading to new diagnostic tools and therapeutic targets. He is a founding member of the Prostate Cancer Research consortium and Chair of the Bio-Resource Management and Implementation group of the consortium were he has established standard operating procedures for the appropriate collection of Tissue, Blood and Urine from men undergoing radical prostatectomy.
William GALLAGHER, Ph.D. [william.gallagher@ucd.ie]
Dr. Gallagher is Associate Professor of Cancer Biology at the UCD Conway Institute. He is also Deputy Co-ordinator of the Cancer Biology Group at the Institute, and serves on the Executive Committee of the British Association for Cancer Research. His research is concerned with transcriptomic and proteomic analysis of cancer-related model systems and biopsies with a view towards biomarker discovery, as well as subsequent high-throughput validation using a combination of tissue microarrays and advanced digital slide scanning technology. He has also established comprehensive SELDI profiling and xenograft model facilities at the UCD Conway Institute that will be availed of in the current program.
Mark LAWLER, Ph.D.
Dr. Lawler is Associate Professor of Molecular Medicine at Trinity College Dublin (TCD), as well as Chief Molecular Geneticist and Director of the Cancer Molecular Genetics Laboratory at St. James's Hospital (a CPA accredited laboratory and the only cancer molecular diagnostics laboratory in Ireland). His research interests include the molecular and cellular basis of cancer, with a view to identifying new biomarkers of disease progression and response and to develop new approaches in the treatment of malignancy. He is currently Chairperson of the St. James's Hospital Cancer Strategy Group, President of the Irish Association of Cancer Research and member of the All-Ireland NCI Implementation Group. He is a founding member of the Prostate Cancer Research consortium and Chair of the Executive Management Team of the consortium.
Stephen PENNINGTON, Ph.D.
Dr. Pennington is Professor of Proteomics at the UCD Conway Institute. His research uses two-dimensional gel electrophoresis (2-DE) and LC approaches, combined with mass spectrometry, for the identification of novel markers in a range of diseases. The multi-user proteomics facility at the UCD Conway Institute now contains state-of-the-art instrumentation and software for 2-DE gel running, image analysis, spot cutting, automated protein digestion, MALDI and electrospray mass spectrometers. The facility is being used to support a series of collaborative research programmes in biomedical sciences including the Prostate Cancer Research Consortium.
Richard O'KENNEDY, Ph.D.
Dr. O'Kennedy is Professor of Biological Sciences in the School of Biotechnology at Dublin City University (DCU). He is a Principal Investigator in the PRTLI- funded National Centre for Sensor Research, the SFI-funded CSET Biomedical Diagnostics Institute and the IDA/BMS-funded Centre for BioAnalytical Sciences. He is a member of the Management Committee of the National Centre for Sensor Research at DCU and principal researcher with the Applied Biochemistry Group. He has specific expertise in the development of novel antibody- and cell-based sensor systems, antibody-based assay development, genetic methods of antibody production and novel antibody labeling systems. A number of reagents, assays, and materials developed in his laboratory have or are being successfully commercialized.
Elaine KAY, M.D.
Dr. Kay is Associate Professor of Pathology at the Royal College of Surgeons in Ireland and is a Consultant Histopathologist at Beaumont Hospital, Dublin. She is also a member of the All-Ireland NCI Implementation Group and serves on a number of medical research ethics committees. Her research is concerned with molecular pathology of a range of cancer types, including prostate, breast and bladder cancer. Her team has considerable expertise in the generation and application of tissue microarrays for biomarker validation studies. She is also using protein lysate arrays for quantitative assessment of putative biomarker expression across multiple specimens. Finally, she also is involved with William Gallagher in the application of digital slide scanning technology to fast-track biomarker validation studies.
Joe DUFFY, Ph.D., F.R.C.Path.
Dr. Duffy is Principal Biochemist at St. Vincent's University Hospital and Adjunct Professor at University College Dublin. For over 20 years, Joe Duffy has been studying genes and proteins involved in cancer metastasis and investigating these as prognostic factors in cancer. He was the first to show that a protein causally involved in experimental metastasis (i.e. uPA) was a prognostic factor in a human cancer (i.e. in breast cancer). This seminal finding has now been confirmed by at least 20 different groups worldwide. Joe Duffy is also a member of a number of international expert panels including the European Group on Tumour Markers (EGTM), The Receptor and Biomarker Group of the European Organization for Research and Treatment into Cancer (EORTC) and the PSA Isoform Review Group (UK). He currently chairs the National Academy of Clinical Biochemistry (USA) Committee for the publication of new guidelines on the clinical use of breast cancer markers.
Des HIGGINS, Ph.D.
Dr. Higgins is Professor of Bioinformatics at the UCD Conway Institute. He has a world-renowned reputation in bioinformatics from his development of the sequence alignment tool, CLUSTAL, articles based around which are some of the most cited publications in the biomedical literature. Of particular relevance to this program is the specialist expertise that his group provides in terms of analysis of gene expression and proteomic data. In particular, they have developed some highly novel approaches for integration of -omic data across technology platforms and between studies, as well as promoter mining.
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