Based on the success ofthe initial 10-year award, the ultimate goals of this COBRE renewal application are to complete the establishment at Dartmouth of a nationally recognized Center for Molecular, Cellular, and Translational Immunological Research, and to transition this COBRE Center for Immunological Research (COBRE-CIR) to an infrastructure-based, freestanding (from COBRE funding), sustainable center in five years. With the foundation of a long-standing Immunology Program, which has now been substantially enhanced by COBRE support, this proposal takes advantage of a highly interactive core of collaborative faculty at Dartmouth Medical School (DMS) and Dartmouth Hitchcock Medical Center (DHMC). With this expanded investigator base, a Phase III COBRE award will provide the resources to build the needed infrastructure to sustain the COBRE-CIR, further grow the Program, and facilitate inter-disciplinary basic science to translational immunological research. This infrastructure will include the continued mentored development of our immunlogical faculty, especially those investigators previously supported by COBRE; expansion ofthe COBRE Cores and their full integration with existing complementary cores and shared services at DMS/DHMC, particularly the Norris Cotton Cancer Center and the other Immunology and """"""""Lung Biology"""""""" COBREs at Dartmouth and the Univesrity of Vermont;and an enhanced Pilot Projdect Program with targeting to mentored, collaborative, and/or translational/human systems research. Together with substantive Institutional commitment by DMS/DHMC, there is confidence that the strong existing cadre of investigators, already expanded and matured by the COBRE mechanism, can be further developed to complete the formation of a sustainable Center for Immunological Research that is grounded in excellent basic science investigation, embraces a translational approach to promote bidirectional bench-to-bedside application of hypothesis-driven research, and has a regional, if not also national, impact.
The immune system is central to a variety of disease states, from protective responses to microbial infections and tumors, to unwanted inflammation and immunopathology characteristic of allergy, autoimmunity, etc. A better understanding of how to regulate the immune system is needed to create better vaccines, or to limit immune responses in syndromes resulting from an overzealous recognition of non-dangerous antigen.
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|Butler, Kiah L; Clancy-Thompson, Eleanor; Mullins, David W (2017) CXCR3+ monocytes/macrophages are required for establishment of pulmonary metastases. Sci Rep 7:45593|
|Mustachio, Lisa Maria; Lu, Yun; Tafe, Laura J et al. (2017) Deubiquitinase USP18 Loss Mislocalizes and Destabilizes KRAS in Lung Cancer. Mol Cancer Res 15:905-914|
|Steinberg, Shannon M; Shabaneh, Tamer B; Zhang, Peisheng et al. (2017) Myeloid Cells That Impair Immunotherapy Are Restored in Melanomas with Acquired Resistance to BRAF Inhibitors. Cancer Res 77:1599-1610|
|Obar, Joshua J; Hohl, Tobias M; Cramer, Robert A (2016) New advances in invasive aspergillosis immunobiology leading the way towards personalized therapeutic approaches. Cytokine 84:63-73|
|Rastad, Jessica L; Green, William R (2016) Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-?. Virology 499:9-22|
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