| Project Title: | Colorectal Cancer Biomarker Discovery | |
| Cancer Site: | Colorectal | |
| Team Coordinator: | Gerrit A. MEIJER, Ph.D | |
| Principal Investigator(s): |
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| Participating Institution(s): |
VU University Medical Center (VUmc), Amsterdam, the Netherlands |
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| Clinical Samples: | Serum/plasma, CRC adenoma and carcinoma tissue | |
| Mouse Model(s): | APC-mutant mice | |
| Technical Approaches: |
HTP MALDI-TOF-MS-based profiling
NanoLC-LTQFTMS Sub-proteomes (Low Mw-, glyco-, surface-, nuclear- proteomes) Label-free protein quantitation iTRAQ quantitation MALDI Tissue Profiling/Imaging Immuno-MS 1D/2DGE Comparative Genomic Hybridization (array-CGH profiling) mRNA-expression profiling (Agilent platform) RNAi Global (genome-wide siRNA kd library, Dharmacon) Tissue microarray / immunohistochemistry Antibody generation (phage display library) Bead-based Multiplexing Assay System |
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Research of the Tumor Profiling Unit of the VUmc Cancer Center Amsterdam, focuses on translational and basic studies aiming to reduce the high death rates from gastrointestinal cancer with a focus on colorectal cancer (CRC). This includes secondary prevention of CRC, and optimized therapy selection for CRC. Concerning secondary prevention, we aim to 1. identify biomarkers that discriminate pre-malignant lesions with low potential to progress into carcinomas ('low-risk' adenomas) from 'high-risk' adenomas (tumor profiling by arrayCGH, transcriptomics, and proteomics), and 2. to identify individuals at increased risk (genetic predisposition) for sporadic cancer (blood profiling by transcriptomics and proteomics). Concerning optimized therapy selection, we aim to follow the response to therapy by analyzing blood samples of CRC patients before and after treatment (blood-profiling by proteomics).
The current program of the VUmc-CCA team will focus on the application of mass spectrometry (MS)-based proteomics to the discovery and quantitation of protein biomarkers for colorectal cancer. This team builds on ample clinical, genomics and proteomics expertise and new state-of-the-art infrastructure in MS and proteomics at VUmc. Three major application development areas are 1. high-throughput peptide profiling of body fluids by magnetic bead-based sample processing off-line coupled to MALDI-TOF-MS, 2. label-free peptide profiling of tissue and body fluid subproteomes by nanoLC-LTQFTMS and 3. the selective enrichment and quantitative analysis of candidate cancer-related genes identified by genomics/transcriptomics/proteomics by targeted tandem mass spectrometry methods. The VUmc-CCA team will be supported by a rapidly growing informatics group, which will develop and implement (open-source) data analysis tools for label-free quantitation of LC-MS datasets. After the discovery and initial validation of candidate CRC biomarkers, our final goal is to develop blood tests for risk assessment and early detection of CRC.
Gerrit A. MEIJER, M.D., Ph.D.
Dr. Gerrit A. Meijer is CRC Team Coordinator, head of the Tumor Profiling Unit.
Connie R. JIMENEZ, Ph.D.
Dr. Connie R. Jimenez is head of the recently established OncoProteomics Laboratory of the Cancer Center Amsterdam at the VUmc, and coordinates the VUmc-clinical proteomics activities in the context of the Center for Medical Systems Biology, a national genomics center of excellence. In 1994, at the Vrije Universiteit in Amsterdam, she pioneered the use of MALDI-TOF-MS for differential display of neuropeptides in single cells and, in 1997, for semi-quantitative neuropeptide profiling directly in tissue homogenates. Since 1997 (while at UCSF in the Burlingame lab), she has worked in the field of proteomics and has ample expertise in the handling of complex biological samples (whole tissue, cells, organelles and more recently body fluids). In 2000, Dr. Jimenez initiated and is still coordinating the Netherlands Proteomics Platform. She is member of the general council of the European Proteomics Association (EuPA) and participates in the operation committee EuPA-HUPO interactions. Moreover, she is member of the biomarker discovery committee of the HUPO-Brain project.
Remond J.A. FIJNEMAN, Ph.D.
Dr. Remond J.A. Fijneman is Research Associate of the Tumor Profiling Unit. He has a strong background in mouse models for human cancer, which he used to dissect the genetic complexity of predisposition to sporadic cancer, and to investigate molecular interactions between epithelial tumor cells and hematopoietic (stromal) cells. Currently, he aims to 1. identify a blood-derived RNA-expression profile indicative of CRC risk that can be used as a pre-likelihood test for CRC screening, and 2. to identify biomarkers for colorectal cancer that can be used for molecular imaging, a project that is carried out together with a Ph.D. student (Meike de Wit, M.Sc.), in collaboration with Philips Research.
Beatriz CARVALHO, Ph.D
Dr. Beatriz Carvalho is Research Associate of the Tumor Profiling Unit. She has a strong background in Comparative Genomic Hybridization and expression arrays, using large series of colon adenoma and carcinoma samples. Based on these data, she currently aims to identify gene(s) that are responsible for adenoma-to-carcinoma progression, a project that is carried out together a Ph.D. student (Anke Hardebol, M.Sc.).
Sander PIERSMA, Ph.D.
Dr. Sander Piersma is Research Associate of the OncoProteomics Laboratory. Dr. Piersma is a biochemist with a background in protein isolation, purification and characterization. Since 2002, he is active in the area of imaging mass spectrometry as well as LC-MS. In 2005, Dr. Piersma published the first mass spectrometry imaging at subcellular resolution. In the OPL, he is leading the nanoLC-LTQFTMS workflows as well as direct tissue profiling/imaging by MALDI-TOF-MS, both with a focus on native peptides and proteins.
Jaco KNOL, Ph.D.
Dr. Jaco Knol is a Ph.D. level research technician of the OncoProteomics Laboratory with ample expertise in molecular biology and biochemistry. Dr. Knol is performing all MALDI-TOF/TOF workflows with a focus on method development for the analysis of tissue (focused on the cell nucleus) and biological fluids using MALDI-TOF-MS for biomarker discovery.
Thang PHAM, Ph.D.
Dr. Thang Pham is Research Associate of the OncoProteomics Laboratory. Dr. Pham is a computer scientist with expertise in pattern recognition. The aim is to implement robust data pre-processing routines that will be combined with multi-variate statistical approaches (supervised and non-supervised) to create reliable statistical models that are validated and robust enough for patient classification and biomarker discovery. Dr. Thang works in close collaboration with data analysis experts in the Depts of Clinical Epidemiology and Biostatistics (Prof. Dr. Maarten Boers), Statistics (Vrije Universiteit Amsterdam, Prof.Dr. Aad van der Vaart), and Computer Science (Vrije Universteit Amsterdam, Dr. Elena Marchiori).
Bauke YLSTRA, Ph.D.
Dr. Bauke Ylstra is head of the VUmc Micro-Array Facility. The VUMC MA-facility offers high resolution array CGH as well as expression arrays (Agilent platform). The facility has several coworkers, including a statistician, Dr. Mark van der Wiel, specialized in 'omics' data analysis. See further.
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