The Mouse Modeling Unit coordinates expertise from the MSK Transgenic, GEMM-ESC and Antitumor core facilities to provide investigators with access to cutting-edge models to explore relationships between genetics and disease phenotypes, and a suite of tools and expertise to analyze these models in depth.
Patient Derived Xenografts (PDXs)
We establish xenograft models from cell lines and tumor samples. Methodologies for cell/tissue implantation include: subcutaneous, intraperitoneal, intravenous, intracardiac, intradermal and orthotopic (lung, liver, stomach, pancreas, colon, spleen, kidney, bladder, bone, brain, prostate, mammary fat pads, ovary, and tongue).
- Sample identification and collection: Tumor samples are obtained from many sources including surgeries, biopsies, autopsies, and fluid drains. Our Research Study Assistants (RSAs) identify patients of interest, obtain and verify IRB consents, liaise with clinical, surgical, and laboratory staff, coordinate sample retrieval and implantation, and then manage clinical annotations in our PDX database.
- Sample implantation, propagation and storage: Samples are processed by the Antitumor Facility staff and implanted s.c. or orthotopically into NSG mice. Tumors that successfully engraft are serially transplanted and, with each passage, samples are collected, processed for analysis, catalogued, and stored in our PDX biobank.
- PDX Databases: We partnered with CRDB and cBIOportal to create an intranet-based database that integrates several modules, allowing researchers to manage raw data, track experimental data, and clinically and genomically annotate samples and models.
- Our growing library currently includes more than 600 individual PDX models representing over 50 different cancer subtypes.
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Elisa de Stanchina
Embryonic Stem Cell-Genetically Engineered Mouse Model (ESC-GEMM) is a conceptually new approach pioneered by the laboratory of Scott Lowe. It is a methodology based on using mouse ES cells carrying conditional disease-associated alleles that, in combination, generate functional models of diseases. By in vitro manipulation, an inducible shRNA or CRISPR/Cas9 cassette can be integrated into these ES cells to create additional genetic complexity, resulting in customized GEMMs amenable to in vivo gene regulation or disruption at different stages of disease. These multi-allelic ES cells can then be used to produce mice with a range of disease-prone genetic backgrounds. Through the use of inducible systems, gene function can then be perturbed in an inducible and reversible manner.
Using this approach, multiple genetic configurations can be studied without the need for expensive, wasteful, and sometimes unfeasible colony breeding. ESC-GEMM thus provides a highly flexible system to interrogate the genetics and biology of cancer initiation, progression and treatment response; it also offers a platform to develop large cohorts of multi-allelic animals for evaluating the contribution of a broad range of candidate ‘disease genes’ simultaneously.
Send email with SUBJECT: ESC-GEMM request to: