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Research Programs

Discipline-based Programs

Cancer Genetics

Collaborative Interactions

Core facilities and special collaborative research programs

1. The Harvard Medical School-Partners Healthcare Center for Genetics and Genomics (HPCGG)

Director: Dr. Raju Kucherlapati

Launched in Fall 2001, supports genetics and genomics in research and clinical medicine.  The HPCGG has enabling genomics technologies for a wide range of research projects.  The HPCGG also operates the Laboratory for Molecular Medicine, a CLIA laboratory capable of performing molecular tests and developing validated assays in collaboration with investigators.  Because of its extensive infrastructure and organization, the HPCGG is able to integrate multiple approaches and sizes of projects easily.

The HPCGG welcomes inquiries from DF/HCC investigators about any aspects of its services.  More detailed information about HPCGG and contacts may be found at: www.hpcgg.org.
 
HPCGG Infrastructure Available-Created to Facilitate High-Throughput Genomics Research:

    1. Genotyping Facility: Affymetrix, Illumina Bead Station, Sequenom, and TaqMan
    2. Microarray Facility: Affymetrix, CGH, DNA arrays, Bioinformatics Analysis
    3. Proteomics Facility: LCQ and LTQ-FT Mass Spectrometry, Sample Preparation Platforms
    4. High-Throughput Sequence Analysis and Resequencing 
    5. Sample Management: DNA Extraction, Cell Line Transformation, Storage  
    6. Gene Modification Facility 
    7. Consultation on Experimental Design
    8. Extensive IT Infrastructure and LIMS for Project Management

2. Mouse SNP Genotyping Service

Director: David Beier, MD, PhD

The Mutation Mapping and Developmental Analysis Project (MMDAP; Brigham and Women’s Hospital, Harvard Medical School), together with the Harvard Partners Center for Genetics and Genomics (HPCGG) and the Broad Institute of MIT and Harvard, offers both whole genome and custom mouse SNP genotyping.  This service’s fixed whole genome panels are suitable for mapping monogenic mutations, modifier loci, quantitative trait loci, and loss-of-heterozygosity loci, as well as for investigating strain contamination and congenic strain generation.  Custom genotyping panels are ideally suited for high-resolution or chromosome-specific mapping projects.  Contact Jennifer Moran, PhD, at 617-525-4720 or jmoran@rics.bwh.harvard.edu for pricing information or questions. 

3. Genomic Resequencing strategies

Click Image to Enlarge

Dr. George Church’s lab has developed a genome resequencing technology that employs digital microfluidic microscopes.  This "Polony" method is described in Science 309(5741):1728-32. Related tools for haplotyping, locating breakpoints, and assessing DNA copy number changes are linked from our web page.  This lab also has resources for large-scale DNA synthesis, mass spectrometry quantitation and high-throughput cell assay image analysis software. 

http://arep.med.harvard.edu/

4. “Interactome” – Yeast two hybrid mapping

Dr. Marc Vidal’s Lab.  To address how complex cellular systems relate to biology, this lab takes the approach, at the scale of the whole proteome, of experimentally modeling protein-protein interaction, or “interactome” networks,  then integrating the resulting interactome maps with other types of functional genomics information. The lab’s goal is to uncover the local and global features underlying the organization of interactome networks and how these organizational features are disrupted in human cancer and other diseases.

Recent progress includes the generation of proteome-scale drafts of interactome maps for C. elegans and human; the integration of interactome networks with dynamic functional information for several biological processes in C. elegans; and the characterization of the principle of modularity and of the effects of limited sampling in interactome networks of the yeast S. cerevisiae.

As a specific example of how effective network integration can be, analysis of a breast cancer network generated by functional integration uncovered a heretofore unappreciated functional association between the BRCA1 breast cancer gene and a novel component of the centrosome, a microtubule organelle responsible for proper segregation of chromosomes at cell division.

The Vidal Laboratory
http://vidal.dfci.harvard.edu

The Center for Cancer Systems Biology
http://ccsb.dfci.harvard.edu

5. Zebrafish Research

Dr. Leonard Zon’s laboratory focuses on the developmental biology of hematopoiesis and cancer.   Over the past five years, this lab has collected over 30 mutants affecting the hematopoietic system.  Some of the mutants represent excellent animal models of human disease; for example, the isolation of the ferroportin iron transporter was based on a mutant zebrafish and subsequently was shown to be mutated in patients with iron overload disorders.

The mutants also represent interesting key regulatory steps in the development of stem cells.  Recently, a mutant was found that lacked blood stem cells and the mutated gene proved to be a caudal related homeoprotein called CDX4.  A Cdx-hox pathway was found to participate in early hematopoietic stem cell development, and overexpression of CDX4 leads to ectopic blood development within the zebrafish embryo and in mouse embryonic stem cells.

The lab has recently developed hematopoietic cell transplantation for the zebrafish using blood cells labeled with green fluorescent protein and DSred.  We were able to image the hematopoietic cells as they migrate to the marrow and to the thymus. 

The laboratory has also developed zebrafish models of cancer.  A screen for cell cycle mutants found 19 mutants; some of these mutants get cancer at a very high rate as heterozygotes based on a carcinogenesis assay.  The mutant genes appear to be new cancer genes and we have used small molecules in a chemical suppressor gene to find chemicals that bypass the mutant cell cycle problem.  We also have generated a melanoma model in the zebrafish system using transgenics—transgenic fish get nevi, and in a combination with a p53 mutant fish develop melanomas.