Descriptions for Grant Writers
Fred Hutchinson Cancer Center investigators who are writing grant applications and need descriptions of the Comparative Medicine shared resource can find them on the Comparative Medicine CenterNet site (access requires Fred Hutch credentials). Descriptions of the overall Fred Hutch Shared Resources program are available on the main Shared Resources grant information page.
Investigators who are writing grant applications and need descriptions of the patient-derived xenograft (PDX) and genetically engineered mouse model (GEMM) teams can find them below.
Publications by Comparative Medicine staff are listed below.
ON THIS PAGE
Citations for CCSG-Support Research | PDX Grant Descriptions | GEMM Grant Descriptions | Publications
Citations for CCSG-Support Research
All publications, press releases, or other documents that cite results from CCSG-supported research must include acknowledgement of the grant and maintain compliance with NIH Public Access Policy. All manuscripts accepted for publication must be submitted to PubMed Central and be assigned a PMCID. Additionally, please reference the Research Resource Identifier (RRID). RRIDs are assigned to cores to help researchers cite key resources in the biomedical literature to improve transparency of research methods.
This research was supported by NIH P30 CA015704 to the Fred Hutch/University of Washington/Seattle Children's Cancer Consortium, which includes the Comparative Medicine Shared Resource, RRID:SCR_022610.
PDX Grant Descriptions
Short Grant Description
The Comparative Medicine (CM) shared resource supports preclinical research through in vivo study support services. Our patient derived xenograft (PDX) team supports researchers in tumor tissue collection, development, propagation and banking of PDX tumors and management of data. We have more than 60 banked PDX tumor models. Dedicated PDX staff provide full-service preclinical study assistance, including PDX mouse model creation, experimental agent testing, and data collection and reporting.
Long Grant Description
The Comparative Medicine (CM) shared resource supports preclinical research through in vivo study support services. Comparative Medicine provides state-of-the-art housing, veterinary care and oversight and laboratory space within an AAALAC-accredited animal facility. The CM shared resource is partially supported by a National Cancer Institute Cancer Center Support Grant to the Fred Hutch/University of Washington Cancer Consortium.
The PDX team provides researchers with assistance ranging from project discussion to complete therapeutic trials in PDX mouse models. Currently, the PDX team's tumor bank houses more than 60 PDX models. The team supports PDX-related studies for multiple investigators within the Cancer Consortium.
PDX Model Creation: The PDX team can support the development of patient tumor tissue as PDX mouse models, with services including implantation, serial repassaging, characterization and banking.
PDX Model Acquisition: The team helps to source and coordinate acquisition of established PDX models from third parties, such as the Jackson Laboratory and the National Institutes of Health’s Patient-Derived Models Repository. These models are revived from their cryopreserved state, implanted and serially repassaged to expand and establish the model, and then used to implant cohorts of mice for treatment studies.
GEMM Grant Descriptions
Short Grant Description
The Comparative Medicine (CM) shared resource supports preclinical research through in vivo study support services. The genetically engineered mouse modeling (GEMM) services team supports investigators through resources and expertise in the design, production and maintenance of transgenic and gene-edited mice. The ability of the GEMM team to manipulate the mouse genome through CRISPR and traditional transgenic technology is invaluable in studying the functions of genes relevant to cancer and other human diseases. The team provides state-of-art mouse genetic manipulations and other critical services for mouse colony production and preservation such as in vitro fertilization, mouse and embryo cryopreservation, speed expansion of mouse colonies and mouse strain rederivation services.
Long Grant Description
The Comparative Medicine (CM) shared resource supports preclinical research through in vivo study support services. Comparative Medicine provides state-of-the-art housing, veterinary care and oversight and laboratory space within an AAALAC-accredited animal facility. The CM shared resource is partially supported by a National Cancer Institute Cancer Center Support Grant to the Fred Hutch/University of Washington Cancer Consortium.
The GEMM team supports investigators through resources and expertise in the design, production and maintenance of transgenic and gene-edited mice. The staff works with investigators to adapt and develop novel technology to create genetically engineered mouse models of varying complexity. The ability of the GEMM team to manipulate the mouse genome is invaluable for studying the functions of genes relevant to cancer and other human diseases.
The GEMM team offers a wide range of services requisite for transgenic mouse production and mouse colony management, and it is equipped with all essential expertise, instrumentation and procedure spaces. The basic molecular biology lab is equipped with all basic instruments essential for the operation of the CRISPR/Cas9 tool (E-Gel Imager, nanophotometer, agarose gel electrophoresis system, -80oC and -20oC freezers, 37oC incubator, and water bath, thermal cyclers, etc.). This setup permits the GEMM team to provide screening assays and genotyping of complex founder animals, vector creation, quality control and quick adoption of novel techniques. A dedicated procedure space within the animal facility (specific pathogen-free space) is equipped with an Eppendorf microinjector and manipulator, a Leica S9D stereomicroscope (with 10x, 20x and 40x objectives), a Gene Pulser Xcell Total System (100/240 V, 50/60 Hz) and an electroporator.
The GEMM team offers the following services:
- CRISPR-mediated gene targeting in mice by pronuclear or cytoplasmic microinjections. The GEMM team can develop genetically engineered mouse models to provide the in vivo tools to answer complex research questions. The team uses leading-edge methods for the creation of unique mouse models, including new genome engineering technologies such as CRISPR/Cas9 gene editing.
- Mouse sperm cryopreservation: The GEMM team offers sperm cryopreservation services for effective mouse colony management. The core collects sperm and cryopreserves it in 21 cryo-straws in a cryopreservation medium within the tightly controlled freezer facility at Fred Hutch.
- Mouse strain cryo-recovery services (in vitro fertilization or direct embryo implantation): The GEMM team can cryo-recover frozen mouse strains. Cryopreserved sperm are used to fertilize oocytes for zygote production through IVF, followed by transplantation into a surrogate mother. Similarly, the team can resuscitate cryopreserved embryos by transferring them into a surrogate mother.
- Mouse strain rederivation services: The adventitious pathogen status of a transgenic mouse line may impact the mice’s breeding efficiency, health and life span and experimental variables such as immune response or microbiota. Adventitious agents are critical research confounders. The GEMM team performs mouse strain rederivation to eliminate adventitious agents when they are identified during quarantine or routine murine health surveillance or as requested by researchers.
- Speed expansion service: The GEMM team can help with the rapid expansion of an age-matched mouse colony via technically challenging IVF and embryo-transfer surgeries.
Selected Publications Made Possible by Comparative Medicine
This is a partial list of publications. For more publications, contact us.
Arkatkar T, Davé V, Cruz Talavera I, Graham JB, Swarts JL, Hughes SM, Bell TA, Hock P, Farrington J, Shaw GD, Kirby A, Fialkow M, Huang ML, Jerome KR, Ferris MT, Hladik F, Schiffer JT, Prlic M, Lund JM. Memory T cells possess an innate-like function in local protection from mucosal infection. J Clin Invest. 2023 May 15;133(10):e162800. doi: 10.1172/JCI162800. PMID: 36951943; PMCID: PMC10178838.
Cabán M, Rodarte JV, Bibby M, Gray MD, Taylor JJ, Pancera M, Boonyaratanakornkit J. Cross-protective antibodies against common endemic respiratory viruses. Nat Commun. 2023 Feb 13;14(1):798. doi: 10.1038/s41467-023-36459-3. PMID: 36781872; PMCID: PMC9923667.
Jana S, Brahma S, Arora S, Wladyka CL, Hoang P, Blinka S, Hough R, Horn JL, Liu Y, Wang LJ, Depeille P, Smith E, Montgomery RB, Lee JK, Haffner MC, Vakar-Lopez F, Grivas P, Wright JL, Lam HM, Black PC, Roose JP, Ryazanov AG, Subramaniam AR, Henikoff S, Hsieh AC. Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression. Cancer Cell. 2023 May 8;41(5):853-870.e13. doi: 10.1016/j.ccell.2023.03.021. Epub 2023 Apr 20. PMID: 37084735; PMCID: PMC10208629
Zhang H, Zhu X, Friesen TJ, Kwak JW, Pisarenko T, Mekvanich S, Velasco MA, Randolph TW, Kargl J, Houghton AM. (2022). Annexin A2/TLR2/MYD88 pathway induces arginase 1 expression in tumor-associated neutrophils. J Clin Invest, 132(22). PMCID: PMC9663166.
Jana S, Brahma S, Arora S, Wladyka CL, Hoang P, Blinka S, Hough R, Horn JL, Liu Y, Wang LJ, Depeille P, Smith E, Montgomery RB, Lee JK, Haffner MC, Vakar-Lopez F, Grivas P, Wright JL, Lam HM, Black PC, Roose JP, Ryazanov AG, Subramaniam AR, Henikoff S, Hsieh AC. Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression. Cancer Cell. 2023 May 8;41(5):853-870.e13. doi: 10.1016/j.ccell.2023.03.021. Epub 2023 Apr 20. PMID: 37084735; PMCID: PMC10208629
Rominger MC, Gupta S, Moorthi S, McSharry M, Kamlapurkar S, O'Brien S, Waldum A, Lo A, Duke F, Lowe AR, Cromwell E, Glabman R, Koehne A, Berger AH. Mutant RIT1 cooperates with YAP to drive an EMT-like lung cancer state. bioRxiv [Preprint]. 2024 Nov 12:2024.11.11.623044. doi: 10.1101/2024.11.11.623044. PMID: 39605726; PMCID: PMC11601272.
Riley AK, Grant M, Snell A, Cromwell E, Vichas A, Moorthi S, Rominger C, Modukuri SP, Urisman A, Castel P, Wan L, Berger AH. The deubiquitinase USP9X regulates RIT1 protein abundance and oncogenic phenotypes. iScience. 2024 Jul 14;27(8):110499. doi: 10.1016/j.isci.2024.110499. PMID: 39161959; PMCID: PMC11332844.
Lee JH, Lee JD, Paulson K, Voillet V, Berndt A, Church C, Lachance K, Park SY, Yamamoto NK, Cromwell EA, Gottardo R, Chapuis AG, Nghiem P. Enhancing immunogenic responses through CDK4/6 and HIF2α inhibition in Merkel cell carcinoma. Heliyon. 2023 Dec 10;10(1):e23521. doi: 10.1016/j.heliyon.2023.e23521. PMID: 38173534; PMCID: PMC10761584.
Jacob J. Kennedy, Amanda Woodcock, Richard G. Ivey, ChenWei Lin, Guy Corral, Eli Hooper, Gregory Martin, Gina Longman, Blake Stancik, Elizabeth A. Cromwell, Jeffrey R. Whiteaker, Lei Zhao, Travis D. Lorentzen, Scott Thielman, and Amanda G. Paulovich.Preserving the Phosphoproteome of Clinical Biopsies Using a Quick-Freeze Collection Device.Biopreservation and Biobanking.Oct 2022.436-445.http://doi.org/10.1089/bio.2022.0068
Lee, J.H. & Lee, J. & Pulliam, T. & Paulson, Kari & Voillet, V. & Berndt, A. & Church, Candice & Lachance, Kristina & Park, S.Y. & Cromwell, E. & Gottardo, R. & Chapuis, Aude & Nghiem, P.. (2022). LB1044 Inhibitors of CDK4/6 and HIF2a induce immunogenic cell death in merkel cell carcinoma cells. Journal of Investigative Dermatology. 142. B38. 10.1016/j.jid.2022.05.1082.
Kinsella S, Evandy CA, Cooper K, Iovino L, deRoos PC, Hopwo KS, Granadier DW, Smith CW, Rafii S, Dudakov JA. Attenuation of apoptotic cell detection triggers thymic regeneration after damage. Cell Rep. 2021; 37 (1): 109789. PMCID: PMC8627669.
Li S, Simoni Y, Zhuang S, Gabel A, Ma S, Chee J, Islas L, Cessna A, Creaney J, Bradley RK, Redwood A, Robinson BW, Newell EW. Characterization of neoantigen-specific T cells in cancer resistant to immune checkpoint therapies. Proc Natl Acad Sci U S A. 2021; 118 (30): PMCID: PMC8325261.
Nishida-Aoki N, Gujral TS. Polypharmacologic Reprogramming of Tumor-Associated Macrophages toward an Inflammatory Phenotype. Cancer Res. 2022; 82 (3): 433-446. PMCID: PMC8847322.
Parayath NN, Hao S, Stephan SB, Koehne AL, Watson CE, Stephan MT. Genetic in situ engineering of myeloid regulatory cells controls inflammation in autoimmunity. J Control Release. 2021; 339553-561. PMCID: PMC8599636.
Vichas A, Riley AK, Nkinsi NT, Kamlapurkar S, Parrish PCR, Lo A, Duke F, Chen J, Fung I, Watson J, Rees M, Gabel AM, Thomas JD, Bradley RK, Lee JK, Hatch EM, Baine MK, Rekhtman N, Ladanyi M, Piccioni F, Berger AH. Integrative oncogene-dependency mapping identifies RIT1 vulnerabilities and synergies in lung cancer. Nat Commun. 2021; 12 (1): 4789. PMCID: PMC8352964.
Zhang F, Parayath NN, Ene CI, et al. Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nat Commun. 2019;10(1):3974. doi:10.1038/s41467-019-11911-5
O'Brien VP, Koehne AL, Dubrulle J, et al. Sustained Helicobacter pylori infection accelerates gastric dysplasia in a mouse model. Life Sci Alliance. 2020;4(2):e202000876. doi:0.26508/lsa.202000967
Haworth KG, Schefter LE, Norgaard ZK, et al. HIV infection results in clonal expansions containing integrations within pathogenesis-related biological pathways. JCI Insight. 2018;3(13):e99127. doi:10.1172/jci.insight.99127
Liu Y, Horn JL, Banda K, et al. The androgen receptor regulates a druggable translational regulon in advanced prostate cancer. Sci Transl Med. 2019;11(503):eaaw4993. doi:10.1126/scitranslmed.aaw4993
Srivastava S, Salter AI, Liggitt D, et al. Logic-gated ROR1 chimeric antigen receptor expression rescues T cell-mediated toxicity to normal tissues and enables selective tumor targeting. Cancer Cell. 2019;35(3):489-503.e8. doi:10.1016/j.ccell.2019.02.003
Zepeda-Rivera, M., Minot, S.S., Bouzek, H. et al. A distinct Fusobacterium nucleatum clade dominates the colorectal cancer niche. Nature 628, 424–432 (2024). https://doi.org/10.1038/s41586-024-07182-w
Kartha N, Gianopulos JE, Schrank Z, Cavender SM, Dobersch S, Kynnap BD, Wallace-Povirk A, Wladyka CL, Santana JF, Kim JC, Yu A, Bridgwater CM, Fuchs K, Dysinger S, Lampano AE, Notta F, Price DH, Hsieh AC, Hingorani SR, Kugel S. Sirtuin 6 is required for the integrated stress response and resistance to inhibition of transcriptional cyclin-dependent kinases. Sci Transl Med. 2023 May 3;15(694):eabn9674. doi: 10.1126/scitranslmed.abn9674. Epub 2023 May 3. PMID: 37134154.