Dix, Richard - Georgia State University

个人简介

Ph.D. Virology Baylor College of Medicine 1978 Molecular Genetics and Biochemistry Cellular, Molecular Biology and Physiology Molecular Genetics / Neuro-Biology, Ocular Virology and Immunology The eye is an immune-privileged site of the body that possesses a number of structural barriers and immunologic strategies to protect against onset and progression of virus-induced retinal disease, thereby preserving vision. Despite these novel barriers and strategies of the host, viruses use a variety of pathogenetic mechanisms to successfully invade retinal tissues and establish acute infection, a process that often leads to destruction of the delicate structural architecture of the retina and ultimately vision loss and blindness.

研究领域

My research program currently focuses on the pathogenesis of retinal diseases caused by human herpesviruses, especially human cytomegalovirus (HCMV) that is responsible for a sight-threatening retinitis in HIV/AIDS patients. These investigations are being pursued using a clinically relevant animal model of mouse cytomegalovirus (MCMV) retinitis unique to my laboratory that employs mice with a retrovirus-induced immunosuppression (MAIDS). The MAIDS model of MCMV retinitis is being used to explore several issues related to the pathogenesis and immunobiology of AIDS-related HCMV retinitis including cytokine immunotherapy for better treatment of the disease in HIV-1-immunosuppressed patients and the precise role of cellular immunity (i.e., perforin-mediated cytotoxicity) in protection against HCMV retinitis in immunologically normal persons. It is noteworthy that these investigations are also important toward a better understanding of HCMV diseases in other immunosuppressed patient populations including those immunosuppressed for bone-marrow or solid-organ transplantation. My laboratory has recently expanded its interests in diseases of the eye to include age-related macular degeneration (AMD), the leading cause of severe irreversible central vision loss and legal blindness in the growing elderly population. At present, the etiology of the disease remains unknown, although the neovascular “wet” form of the disease is associated with formation of new blood vessels within retinal tissues. In close collaboration with an ocular immunology research laboratory at Duke University, we are participating in clinical studies as well as experimental studies using a mouse model of choroidal neovascularization to test the novel hypothesis that AMD is an inflammatory disease in which persistent HCMV infection of circulating macrophages plays a key cofactor role in disease pathogenesis. These investigations may lead to new paradigms of disease pathogenesis for better diagnosis and management of AMD in the clinical setting.

近期论文

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Reduced frequency of murine cytomegalovirus retinitis in C57BL/6 mice correlates with low levels of suppressor of cytokine signaling (SOCS)1 and SOCS3 expression within the eye during corticosteroid-induced immunosuppression. Alston CI, Dix RD. Cytokine. 2017 May 27;97:38-41. doi: 10.1016/j.cyto.2017.05.021. [Epub ahead of print] Murine cytomegalovirus infection of mouse macrophages stimulates early expression of suppressor of cytokine signaling (SOCS)1 and SOCS3. Alston CI, Dix RD. PLoS One. 2017 Feb 9;12(2):e0171812. doi: 10.1371/journal.pone.0171812. eCollection 2017. Viral forensic genomics reveals the relatedness of classic herpes simplex virus strains KOS, KOS63, and KOS79. Bowen CD, Renner DW, Shreve JT, Tafuri Y, Payne KM, Dix RD, Kinchington PR, Gatherer D, Szpara ML. Virology. 2016 May;492:179-86. doi: 10.1016/j.virol.2016.02.013. Epub 2016 Mar 21. Murine cytomegalovirus downregulates interleukin-17 in mice with retrovirus-induced immunosuppression that are susceptible to experimental cytomegalovirus retinitis. Blalock EL, Chien H, Dix RD. Cytokine. 2013 Mar;61(3):862-75. doi: 10.1016/j.cyto.2013.01.009. Epub 2013 Feb 14. Evidence for multiple cell death pathways during development of experimental cytomegalovirus retinitis in mice with retrovirus-induced immunosuppression: apoptosis, necroptosis, and pyroptosis. Chien H, Dix RD. J Virol. 2012 Oct;86(20):10961-78. Epub 2012 Jul 25. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization. Cousins SW, Espinosa-Heidmann DG, Miller DM, Pereira-Simon S, Hernandez EP, Chien H, Meier-Jewett C, Dix RD. PLoS Pathog. 2012;8(4):e1002671. doi: 10.1371/journal.ppat.1002671. Epub 2012 Apr 26. Systemic reduction of interleukin-4 or interleukin-10 fails to reduce the frequency or severity of experimental cytomegalovirus retinitis in mice with retrovirus-induced immunosuppression. Blalock EL, Chien H, Dix RD. Ophthalmol Eye Dis. 2012 Sep 25;4:79-90. doi: 10.4137/OED.S10294. Print 2012. Nicotine treatment alters NF-kappaB expression in human cytomegalovirus-infected ARPE-19 cells. Buckner AE, Dix RD. Curr Eye Res. 2006 Feb;31(2):191-8.