A Conversation With Dr. St. Leger
I was recruited to the University of Pittsburgh's Department of Ophthalmology to run the Ocular Microbiome and Immunity Laboratory. The main focus of my current lab is understanding how microbes interact with the host immune system to mediate ocular surface disease. With that, I inherited his R01 grant that is focused on how HSV-1 and the associated immune response disrupts the corneal nerve landscape resulting in blinding pathogenesis. Concurrently, I supervise research related to the microbiome and ocular health and have continued Bob Hendricks' legacy of assessing the immune response against HSV-1 infection. During this time at the University of Pittsburgh, I have published my first fully independent publication. In addition to my research training, I have enrolled in the University of Pittsburgh Mentoring Academy, which is an eight-session course on all matters related to mentoring to include diversity, ethical data acquisition and interpretation, and authorship. These courses, in my opinion, have provided me with critical leadership and administrative skills, which will enhance my effectiveness as a PI.
Kate Carroll, PhD - Postdoctoral Associate
Dana Previte, PhD - Postdoctoral Associate
Ben Treat, PhD - Postdoctoral Associate
Jackie Shane, PhD - Postdoctoral Associate
Hongmin Yu, PhD - Research Assistant Professor
Education & Training
- 2012-2017 Postdoctoral Fellow, National Eye Institute, NIH, Bethesda, MD
- 2004-2008 BS, Biological Sciences, University of Pittsburgh, Pittsburgh, PA
- 2008-2012 PhD, Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA
- St Leger AJ, Hansen AM, Karauzum H, Horai R, Yu CR, Laurence A, Mayer-Barber KD, Silver P, Villasmil R, Egwuagu C, Datta SK, Caspi RR. STAT-3-independent production of IL-17 by mouse innate-like αβ T cells controls ocular infection. J Exp Med. 2018 Apr 2;215(4):1079-1090. PubMed PMID: 29490936.
- St Leger AJ, Desai JV, Drummond RA, Kugadas A, Almaghrabi F, Silver P, Raychaudhuri K, Gadjeva M, Iwakura Y, Lionakis MS, Caspi RR. An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells. Immunity. 2017 Jul 18;47(1):148-158.e5. PubMed PMID: 28709803; PubMed Central PMCID: PMC5553552 (Highlighted by JAMA, Time Magazine, F1000, and others).
- St Leger AJ, Jeon S, Hendricks RL. Broadening the repertoire of functional herpes simplex virus type 1-specific CD8+ T cells reduces viral reactivation from latency in sensory ganglia. J Immunol. 2013 Sep 1;191(5):2258-65. PubMed PMID: 23878317; PubMed Central PMCID: PMC3779892.
- St Leger AJ, Peters B, Sidney J, Sette A, Hendricks RL. Defining the herpes simplex virus-specific CD8+ T cell repertoire in C57BL/6 mice. J Immunol. 2011 Apr 1;186(7):3927-33. PubMed PMID: 21357536; PubMed Central PMCID: PMC3308013.
Complete List of Published Work in https://www.ncbi.nlm.nih.gov/myncbi/1DAqB-XXCMakA/bibliography/48905042/...
We have pioneered research in a historically understudied area of ophthalmology, the ocular microbiome and its effect(s) on ocular disease. Normally a highly contentious topic in ophthalmology, the ocular microbiome does, indeed, tune local immunity to prevent fungal and bacterial infection. Now, the St. Leger lab aims to extend those findings to explore how ocular resident bacteria may modulate immunity against viral infections like herpes simplex virus type 1 (HSV-1), which have the potential cause blindness. To this end, the laboratory uses Corynebacterium masitidis as a candidate colonizer to explore how the ocular immunity is developed and maintained. Further, the lab has a keen interest in understanding mechanisms controlling gd T cells, which are critical for protection of the ocular surface from disease.
Future goals include the development of novel probiotic-like therapies for the treatment of diseases at the ocular surface. In addition, we are interested in how the local microbiome may affect intraocular diseases like glaucoma or age-related macular degeneration where the microbiome has been implicated but not proven for the development and progression of disease.
A separate arm of research in the laboratory focuses on investigating how corneal nerves affect the development of ocular disease. In healthy individuals, the cornea, which is the most densely innervated tissue in the body, is innervated by sensory nerves that control the blink reflex and allow the eye to wash away potential pathogens, allergens, and/or irritants. After infection with HSV-1, corneal sensory nerves retract and are replaced with sympathetic nerves, which lack the ability to sense stimuli. As a result, the infected eye loses the ability to blink, which leaves the ocular surface susceptible to trauma and drying. We hypothesize that this mechanism is largely responsible for the disease associated with HSV-1 infection. Current research in the lab focuses on identifying specific factors regulating sensory nerve retraction and sympathetic nerve growth in hopes of developing novel therapies that preserve blink reflexes.
National Eye Institute