The overarching goal of Core 1 is to provide the infrastructure and professional expertise needed to bank primary leukemia, colon, and pancreatic cancer specimens, establish patient-derived xenograft (PDX), organoid, and cell models, and make these patient-derived resources available to all Program investigators, thereby facilitating the translational and laboratory-based research performed by CSBC investigators in Projects 1 and 2. Both projects will require access to patient samples and cells derived from PDX and organoid models. The core supports 3 functions: (1) cryopreservation and distribution of primary cells from patients with leukemia, colon, and pancreatic cancer, (2) establishment, characterization, and distribution of xenograft, organoid, and cell culture models of these diseases, and (3) isolation of cell populations from primary tumor samples and tissue models for single cell analysis. The functions of the core include documentation and tracking of informed consent, isolation and cryopreservation of viable tissue, plasma or serum, and genomic DNA from patient samples and distribution of samples to CSBC investigators. A large number of primary leukemia, colon and pancreatic tumor samples are currently available in our existing repositories for use by Project Investigators. Additional samples will be acquired from patients routinely evaluated in our gastrointestinal oncologic and hematologic malignancies clinics. In addition to distributing primary cells to program investigators, Core 1 will also maintain and distribute a bank of well characterized PDXs selected for passage in immunocompromised mice. Methods for engrafting leukemia cells and primary epithelial tumor tissues in immunodeficient mice are now well established, and we and others have successfully used PDX models for drug testing. Organoid culture approaches will be used to complement the PDX effort, and will provide an additional way of propagating and segregating patient-derived epithelial tumor cells and stromal cells. Core 1 will maintain a bank of PDX models and organoids and distribute to program investigators as needed. Core 1 will be jointly directed by Drs. William Hahn and Dr. David Weinstock. Dr. Hahn is a medical oncologist who directs the DFCI Center for Cancer Genome Discovery (CCGD). He also works closely with the Division of Gastrointestinal Oncology at DFCI and has helped establish an organoid and PDX repository derived from primary and metastatic pancreatic and colon cancer samples. Working with the CCGD, Dr. Hahn's laboratory has created a pipeline for the genomic characterization of consented patient derived samples. Dr. Weinstock is a medical oncologist and directs the DFCI Hematologic Malignancy PDX repository, which already contains >200 transplantable leukemia PDX models that have been cryopreserved and undergone genome-wide transcriptome analysis, targeted DNA sequencing, immunophenotyping, and additional molecular characterization. Thus, Core 1 has extensive experience in the processing, cryopreservation, flow cytometric analysis, purification, propagation, banking, and genomic characterization of primary specimens and tumor models, as well as their use in preclinical drug evaluation.
| Mead, Benjamin E; Ordovas-Montanes, Jose; Braun, Alexandra P et al. (2018) Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol 16:62 |
| Kimmerling, Robert J; Prakadan, Sanjay M; Gupta, Alejandro J et al. (2018) Linking single-cell measurements of mass, growth rate, and gene expression. Genome Biol 19:207 |
| Luskin, Marlise R; Murakami, Mark A; Manalis, Scott R et al. (2018) Targeting minimal residual disease: a path to cure? Nat Rev Cancer 18:255-263 |
| Ordovas-Montanes, Jose; Dwyer, Daniel F; Nyquist, Sarah K et al. (2018) Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature 560:649-654 |
| Cetin, Arif E; Stevens, Mark M; Calistri, Nicholas L et al. (2017) Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation. Nat Commun 8:1613 |
| Shalek, Alex K; Benson, Mikael (2017) Single-cell analyses to tailor treatments. Sci Transl Med 9: |
