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个人简介

Ph.D. Immunology & Molecular Pathogenesis Emory University, 2002 Cellular, Molecular Biology and Physiology Group Tumor Immunology and Human Adenovirus Infection and Leukemia

研究领域

Tumor Immunology and Human Adenovirus Infection in Lymphocytes My laboratory conducts research in the areas of cellular and molecular immunology, as well as investigating the association of human adenovirus with lymphocytes. Ongoing studies involve (1) the analysis of basic immunologic mechanisms and principles against self-cells from diverse tissues, (2) analysis of immune cell interactions with damaged or malignant cells, and (3) investigating the possibility that human species C adenovirus infections in lymphocytes can initiate acute leukemia. Immunogenic Modulation by Radiation One of the major research thrusts in our lab is to examine the effects of ionizing radiation on gene expression in diverse cells to gain further insights into the mechanistic link between irradiation and increased attack by immune cells. Research focuses on those factors that will enhance the activity of effector cytotoxic T lymphocytes (CTL), with emphasis on the effects of ionizing radiation on the immunogenicity of cells that survive radiation. Along these lines we are evaluating: 1) changes in the expression of genes within irradiated cells that modulate effector CTL behavior, 2) the molecular mechanisms of altered gene expression operating in cells surviving radiation, and 3) if immunogenic modulation is similar across cells from diverse tissues. Additional studies focus on modulation of factors occurring within irradiated cells that could activate or regulate other immune cells, such as regulatory T cells and dendritic cells. The laboratory performs investigative research with the goal of increasing our understanding of how attack of damaged and/or malignant self-cells is regulated. A better understanding of these basic immunology principles could impact the design of immunologic strategies for the treatment of cancer and other diseases. Our experimental strategies utilize several techniques in cell and molecular biology including in vitro cell proliferation and apoptotic assays, cytokine production and quantitation, real-time Q-PCR, flow cytometric analysis, immunoblotting techniques, siRNA gene silencing, and in vitro human CTL lytic assays. Adenovirus infection of lymphocytes and leukemia: Research is focused on the study of a human tumor viruses that persistently infect lymphocytes. Our previous studies evaluated the molecular characteristics of natural adenovirus infections in human lymphocytes, with emphasis on identifying lymphocyte cell populations in human tonsils and adenoids that harbor the common species C adenovirus DNA. In addition, the molecular dynamics of adenovirus persistence/latency in these naturally infected lymphocytes were examined by evaluating viral DNA replication, transcription, and protein expression. Current research is focused on gaining further insights into the relationship between prenatal adenovirus infection of lymphocytes and childhood leukemia. The goal is to characterize the latent or persistent phase of subgroup C adenovirus life cycle in humans and to reveal wether this virus contributes to some acute leukemia’s in children. If research can understand the mechanisms of latency in lymphocytes, this information can be used to target vaccines for the purpose of prevention of acute leukemia in childhood. The experimental strategies utilize for these studies include a variety of techniques, such as lymphocyte isolation, lymphocyte cell culture, immunohistochemistry, flow cytometry, real time Q-PCR, DNA purification, detection of leukemia associated gene translocations, and virus propagation and purification.

近期论文

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Limited but durable changes to cellular gene expression in a model of latent adenovirus infection are reflected in childhood leukemic cell lines. Ornelles DA, Gooding LR, Dickherber ML, Policard M, Garnett-Benson C. Virology. 2016 Jul;494:67-77. doi: 10.1016/j.virol.2016.03.015. Epub 2016 Apr 14. Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade. Kumari A, Garnett-Benson C. BMC Res Notes. 2016 Feb 13;9:92. doi: 10.1186/s13104-016-1914-9. Combination Treatment with Sublethal Ionizing Radiation and the Proteasome Inhibitor, Bortezomib, Enhances Death-Receptor Mediated Apoptosis and Anti-Tumor Immune Attack. Cacan E, Spring AM, Kumari A, Greer SF, Garnett-Benson C. Int J Mol Sci. 2015 Dec 21;16(12):30405-21. doi: 10.3390/ijms161226238. Immunomodulatory effects of radiation: what is next for cancer therapy? Kumari A, Simon SS, Moody TD, Garnett-Benson C. Future Oncol. 2016 Jan;12(2):239-56. doi: 10.2217/fon.15.300. Epub 2015 Dec 1. Review. Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases. Cacan E, Greer SF, Garnett-Benson C. Int J Oncol. 2015 Dec;47(6):2264-75. doi: 10.3892/ijo.2015.3192. Epub 2015 Oct 7. Neonatal infection with species C adenoviruses confirmed in viable cord blood lymphocytes. Ornelles DA, Gooding LR, Garnett-Benson C. PLoS One. 2015 Mar 12;10(3):e0119256. doi: 10.1371/journal.pone.0119256. eCollection 2015. Combination regimens of radiation therapy and therapeutic cancer vaccines: mechanisms and opportunities. Garnett-Benson C, Hodge JW, Gameiro SR. Semin Radiat Oncol. 2015 Jan;25(1):46-53. doi: 10.1016/j.semradonc.2014.07.002. Review. Radiation-induced modulation of costimulatory and coinhibitory T-cell signaling molecules on human prostate carcinoma cells promotes productive antitumor immune interactions. Bernstein MB, Garnett CT, Zhang H, Velcich A, Wattenberg MM, Gameiro SR, Kalnicki S, Hodge JW, Guha C. Cancer Biother Radiopharm. 2014 May;29(4):153-61. doi: 10.1089/cbr.2013.1578. Epub 2014 Apr 2.

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