Ph.D.: 1987, University of Texas Medical Branch, Galveston, TX
Awards and Honors:
Stanton L. Young Chair in Ophthalmology
Program Director, NIH/NEI Vision Science Training Grant
LSU Health Sciences Center at New Orleans; University of Alabama at Birmingham
Neuroimmunology; Mucosal Immunology with an emphasis on the eye; herpes simplex virus type 1-induced lymphangiogenesis and encephalitis, vaccine development
GPiBS Immunology, Immunity in Disease, Advanced Immunology, and Dental Microbiology
Office: DMEI 415
Corneal Lymphatics and Adaptive Immunity
Neovascularization in the normally avascular cornea can lead to a compromised visual axis. Within the term “neovascularization” is a blood component referred to as hemangiogenesis and a lymphatic component referred to as lymphangiogenesis. Relative to HSV-1 infection, only hemangiogenesis has been investigated. Our published work convincingly demonstrates lymphangiogenesis is strongly induced by an immediate early gene product of he virus. Currently, we are investigating the contribution of soluble factors likely produced by resident cells found in the cornea that drive and maintain neovascularization after the viral insult has cleared (Fig. 1). Plans include investigating signal cascades activated by these soluble factors related to sprouting of vessels and movement of leukocytes in the cornea. This work is funded by R01 EY021238 through 2020.
The Neuroimmunology of HSV-1 infection
Herpes simplex virus type 1 (HSV-1) is one of the most common neurotropic pathogens in humans with a seroprevalence rate increasing up to 60-80% by the 5th decade of life. Clinical diseases associated with HSV-1 include herpetic stromal keratitis, the leading cause of infectious corneal blindness in the industrialized world, and frank sporadic encephalitis, a rare (1-2 cases/250,000 individuals/year) but debilitating disease that can result in death. Recently, we have identified a unique area of the brain, the ependyma (EP), that harbors lytic infection during viral latency at other peripheral and central nervous system sites (Fig. 2). Immunologically, we find resident memory T cells remain at relatively high levels in the EP but they develop an anergic profile over time. Further characterization of the adaptive immune response including B lymphocytes in this region is planned.
Ocular HSV-1 Vaccine
HSV-1 infection of the eye can have serious consequences including blindness. In the corneal clinic of the Dean McGee Eye Institute, we over 200 patients/year due to ocular HSV-1 disease. There is no cure for HSV-1 infection as intervention does not clear the pathogen but only resolves the acute episode of disease. We are currently investigating a novel vaccine (termed HSV-1 0ΔNLS) that shows significant promise in preventing the acquisition of HSV-1 infection and the associated pathology in a mouse model (Fig. 3). The project consists of defining the immune components and mechanism(s) that correlate with the efficacy of the vaccine and preservation of the visual axis. This work is funded by R01 AI053108 to April, 2022.
Figure 3. Representative photographs of mice 8 days post-infection. Mice vaccinated with HSV-1 0ΔNLS maintained a healthy appearance, while mice vaccinated with the gD-2 subunit developed periocular edema and head swelling. Naive mice developed viral lesions in the periocular skin in addition to head swelling. Taken from J. Immunol. 2017, 199:1898-1911.
Current Lab Personnel:
Grzegorz Gmyrek, PhD – Staff scientist
Adrian Filiberti, PhD – Postdoctoral fellow
Renee Sallack – Lab technician
Taken from 136 peer-reviewed articles:
- Gurung, H.R., M.M. Carr, and D.J.J. Carr. 2017. Corneal lymphatics drive the CD8+ T cell immune response to HSV type 1. Immunol. Cell Biol., 95:87-98. PMCID: PMC5209249
- Royer, D.J., M.M. Carr, A.J. Chucair-Elliott, W.P. Halford, and D.J.J. Carr. 2017. Impact of type 1 interferon on the safety and immunogenicity of an experimental live-attenuated herpes simplex virus type 1 vaccine in mice. J. Virol. 91(7). pii: e02342-16. PMCID: PMC5355590
- Chucair-Elliott, A.J., M.M. Carr, and D.J.J. Carr. 2017. Long-term consequences of topical dexamethasone treatment during acute cornea HSV-1 infection on the immune system. J. Leukoc. Biol. 101:1253-1261. PMCID: PMC5380376
- Menendez, C.M. and D.J.J. Carr. 2017. Herpes Simplex Virus-1 infects the olfactory bulb shortly following ocular infection and exhibits a long-term inflammatory profile in the form of effector and HSV-1 specific T cells. J. Neuroinflamm. 14:124. PMCID: PMC5481928
- Royer, D.J., M.M. Carr, H.R. Gurung, W.P. Halford, and D.J.J. Carr. 2017. The neonatal Fc receptor (FcRn) and complement fixation facilitate prophylactic vaccine-mediated humoral protection against viral infection in the ocular mucosa. J. Immunol. 199:1898-1911. PMCID: PMC5656400
- Chucair-Elliott, A.J., H.R. Gurung, M.M. Carr, and D.J.J. Carr. 2017. Colony Stimulating Factor-1 Receptor Expressing cells infiltrating the cornea control corneal nerve degeneration in response to HSV-1 infection. Invest. Ophthalmol. Vis. Sci. 58:4670-4682. PMCID: PMC5597033
- Gurung, H.R., M.M. Carr, K. Bryant, A.J. Chucair-Elliott, and D.J.J. Carr. 2018. Neutralization of fibroblast growth factor-2 (FGF-2) blocks HSV-1-induced corneal lymphangiogenesis. Mucosal Immunol. 11:172-185. PMCID: PMC5628112
- Royer, D.J., M.H. Elliott, Y.Z. Le, and D.J.J. Carr. 2018. Corneal epithelial cells exhibit myeloid characteristics and present antigen via MHC class II. Invest. Ophthalmol. Vis. Sci. 59:1512-1522. PMCID: PMC5861930