Specialized Histopathology Services Core
The Specialized Histopathology Services Core provides professional and technical research pathology services to members working in diverse organisms, including man, non-human primates, rodents, and zebrafish. The core provides routine histology services, performs histochemical and immunohistochemical stains and in situ hybridization, and also assists in experimental design and the development, application, and interpretation of new biomarker tests.
Examples of projects the core has provided services for include:
One focus of the laboratory of Alan D’Andrea, MD (DFCI), is the analysis of USP -/- knockout mice. The Fanconi anemia (FA) pathway is necessary for the repair of DNA crosslinks and is regulated in part by the monoubiquitination and deubiquitination of FANCD2. Deubiquitination of FANCD2 is mediated by the ubiquitin protease, USP1. Work recently published in Developmental Cell demonstrated that knockout of mouse Usp1 results in increased perinatal lethality, male infertility, DNA cross-linker hypersensitivity, and an FA phenotype. Usp1-/- mouse cells had increased levels of monoubiquitinated Fancd2 in chromatin and exhibited impaired Fancd2 foci assembly and a defect in homologous recombination repair, implicating Usp1 as a downstream component of the FA pathway.
The Specialized Histopathology Services Core was responsible for the analysis of the histopathology of the Usp1-/- mice and developed immunohistochemical stains for Usp1.
Mouse Model of AF4-MLL-associated ALL
Scott Armstrong, MD, PhD (CHB), used a mouse model to study a form of human B cell acute lymphoblastic leukemia (B-ALL) associated with a 4;11 chromosomal translocation, a mutation that produces a chimeric MLL-AF4 gene and predicts for a particularly poor prognosis. In a paper published in Cancer Cell, Armstrong demonstrated that many genes in murine and in human ALLs associated with MLL-AF4 show increased methylation on lysine 79 of histone 3 (H3K79) and that this elevation correlates with enhanced gene expression. Furthermore, suppression of H3K79 methylation inhibited the expression of genes that are turned on by the MLL-AF4 fusion protein. These data demonstrated that the proteins that are responsible for H3K79 methylation in MLL-AF4 leukemias are potential therapeutic targets in this disease and that MLL-AF4 mouse model may be useful for conducting preclinical trials of “epigenetic” therapeutic agents.
The Specialized Histopathology Services Core was responsible for the pathologic work-up of leukemias in the AF4-MLL mice.
Contact information and locations:
Brigham and Women's Hospital
75 Francis St. Thorn 604/603B
Core Director: Jon Aster
Associate Pathologist: Jeffery L. Kutok, Sabina Signoretti
Technical Contact: Donna Skinner; 617-525-7434
MGH East location
Massachusetts General Hospital
East CNY6, 6122
Core Co-Director: Anat Stemmer-Rachamimov
Associate Pathologist: Chin-Lee Wu
Technical Contact: Anna Kreshock; 617-726-5510
Please download the instructions on how to Get Started using the Pathology Cores.