Description of Research Expertise:
My laboratory incorporates both basic science research and clinical investigation to examine the role of innate immunity, in particular monocytes/macrophages, in regulating tumor biology in pancreas cancer as well as other upper gastrointestinal malignancies. Our central hypothesis is that macrophages are key regulators of tumor biology.
Clinical research in the laboratory uses patient-derived samples to understand the role of macrophage biology in metastatic disease and therapeutic efficacy.
Preclinical research in the laboratory uses a genetically engineered mouse model of pancreas cancer in combination with advanced imaging strategies to study macrophage biology within the tumor microenvironment. This preclinical research platform allows for the study of basic immune biology within the tumor microenvironment as well as the rapid screening of novel immunotherapeutic strategies, including cell and gene therapies, for the treatment of cancer.
Studies in the laboratory focus on understanding 1) the signaling pathways that regulate cross-talk between macrophages and tumor cells in vivo, 2) the role of hematopoietic and non-hematopoietic cells in regulating macrophage biology within tumors, 3) the cellular trafficking of macrophages to primary and metastatic lesions, 4) strategies to harness macrophages for anti-tumor therapy, and 5) the impact of chemotherapy/radiation therapy on macrophage biology within tumors.
Vonderheide RH, Bajor DL, Winograd R, Evans RA, Bayne LJ, Beatty GL.: CD40 immunotherapy for pancreatic cancer Cancer Immunol Immunother 62 (5): 949-54,2013.
Maus MV, Haas AR, Beatty GL, Albelda SM, Levine BL, Liu X, Zhao Y, Kalos M, June CH.: T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res 1 (1): 26-31,2013 .
Bayne, L.J., Beatty, G.L., Jhala, N., Clark, C.E., Rhim, A.D., Stanger, B.Z., and R.H. Vonderheide: Tumor-derived granulocyte-macrophage colony stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer Cancer Cell 21 : 822-35.,2012 .
Rhim AD, Mirek ET, Aiello, NM, Maitra A, Bailey J.M, McCallister F, Reichert M, Beatty GL, Rustgi AK, Vonderheide RH, Leach SD, BZ Stanger: EMT and dissemination precede pancreatic tumor formation Cell 148 : 349-61,2012.
Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun WJ, Huhn RD, Song WR, Li DG, Sharp LL, Torigian DA, O'Dwyer PJ, Vonderheide RH: CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans. Science 331 (6024): 1612-1616,2011.
Beatty GL, Smith JS, Reshef R, Patel KP, Colligon TA, Vance BA, Frey NV, Johnson FB, Porter DL, Vonderheide RH: Functional Unresponsiveness and Replicative Senescence of Myeloid Leukemia Antigen-specific CD8(+) T Cells After Allogeneic Stem Cell Transplantation. Clin Cancer Res 15 (15): 4944-4953,2009.
Clark CE, Beatty GL, Vonderheide RH: Immunosurveillance of pancreatic adenocarcinoma: Insights from genetically engineered mouse models of cancer. Cancer Lett 279 (1): 1-7,2009.
Dominiecki ME, Beatty GL, Pan ZK, Neeson P, Paterson Y: Tumor sensitivity to IFN-gamma is required for successful antigen-specific immunotherapy of a transplantable mouse tumor model for HPV-transformed tumors. Cancer Immunol Immunother 54 (5): 477-488,2005.
Beatty GL, Paterson Y: IFN-gamma signaling in antigen loss tumor variants plays a role in the bystander killing effect induced by recombinant Listeria. Federation of American Societies for Experimental Biology Journal 13 (4): A297-A297,1999.
Beatty GL, Paterson Y: IFN-gamma can promote tumor evasion of the immune system in vivo by down-regulating cellular levels of an endogenous tumor antigen. J Immunol 165 (10): 5502-5508,2000.
Beatty GL, Paterson Y: IFN-gamma-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4(+) T cells requires tumor responsiveness to IFN-gamma. J Immunol 166 (4): 2276-2282,2001.