Eric Pearlman

picture of Eric  Pearlman

Director, Institute for Immunology, Physiology & Biophysics
School of Medicine
Professor, Ophthalmology
School of Medicine

Ph.D.

Phone: 949 824 1867
Email: epearlma@uci.edu

University of California, Irvine

Mail Code: 4375
Irvine, CA 92697
Research Interests
Innate immunity, bacterial infections, fungal infections, neutrophils, keratitis
Academic Distinctions
1997 Burroughs Wellcome Foundation New Investigator Award
2004 University of Western Australia Raine Foundation Visiting Professorship
2006 - Research to Prevent Blindness Foundation: Senior Investigator Award
2010 Alcon Research Institute award
2011-2015 Page-Reinhart Endowed Professorship, Case Western Reserve University
2015 - present Director, Institute for Immunology, UCI
2015 Chancellor’s Professor, UC Irvine
Appointments
1994-2000 Assistant Professor, Departments of Medicine and Ophthalmology, Case Western Reserve
University, Cleveland, OH
2000-2002 Associate Professor, Departments of Medicine and Ophthalmology, Case Western Reserve University, Cleveland, OH
2002-2004 Associate Professor, Center for Global Health & Diseases and Department of Ophthalmology
2004-2014 Professor, Department of Ophthalmology, Case Western Reserve University, Cleveland.
2004-2014 Director of Research, Department of Ophthalmology and Visual Sciences, CWRU
2015 Director of the Institute for Immunology, University of California at Irvine
2015 Professor, Departments of Ophthalmology, and Physiology and Biophysics, UC Irvine
Research Abstract
My research program has focused on the innate immune response to parasitic, fungal, and bacterial infections, which has been NIH funded for over 20 years. My earlier studies examined the host response to the parasitic nematode Onchocerca volvulus, which causes ocular onchocerciasis (river blindness), and we reported that endosymbiotic Wolbachia bacteria have a major role in inducing corneal inflammation (Science, 2002). Subsequently, my research program has been examining blinding fungal and bacterial infections of the cornea (keratitis), and is funded by two RO1 grants from the National Eye Institute. These studies examine the role of neutrophils and inflammatory monocytes in immune regulation, microbial killing and in tissue damage. As Director of the Institute for Immunology I run the T32 training grant at UCI that covers 4 pre-doctoral positions per year. I have trained 8 pre-doctoral students and 18 post-doctoral fellows, many of whom have continued in academia.
Publications
Pathogenesis of bacterial keratitis: EY14362 was first awarded in 2004 with the goal of understanding the role of Toll Like Receptors (TLR) in corneal inflammation. In the first funding period, we characterized TLR signaling in the corneal epithelial cells and in infiltrating macrophages and neutrophils, resulting in multiple papers in the Journal of Biological Chemistry, J. Immunol, J. Leukocyte Biology, and IOVS. Subsequent studies with Arne Rietsch at CWRU characterized TLR signaling in Pseudomonas aeruginosa keratitis, which we reported in 2010 in J Immunol (PMC3392180). We also identified the ADPRT region of ExoS and ExoT as the essential P. aeruginosa type III secretion (T3SS) virulence factors in keratitis (J. Immunol 2012. PMC3273577). We continued this collaboration after I moved to UCI, demonstrating that ExoS enhances P. aeruginosa survival in human neutrophils by inhibiting ROS production by ADP ribosylating Ras and thereby blocking NADPH oxidase assembly.
Our studies in India showed that IL-1ß gene expression was elevated in human corneal ulcers caused by bacteria, which were mostly comprised of neutrophils (PLoS One 2013). Using murine models of P. aeruginosa and Strep pneumoniae keratitis, we showed that IL-1ß plays an essential role in bacterial clearance, and that neutrophils were the predominant source of cleaved, bioactive IL-1ß. Although in P. aeruginosa keratitis, neutrophils use elastase to cleave IL-1ß, Strep pneumoniae pneumolysin activates the NLRP3 inflammasome and caspase-1 cleaves IL-1ß. Also, in marked contrast to macrophages, neutrophils release bioactive IL-1ß in the absence of pyroptotic cell death. As a continued collaboration with George Dubyak, ongoing studies are examining the role of Gasdermin D and autophagy in mediating secretion of bioactive IL-1ß from live neutrophils.
1. Vareechon C, S.E. Zmina, M. Karmakar, E. Pearlman, and A. Rietsch. (2017) Pseudomonas aeruginosa Effector ExoS Inhibits ROS Production in Human Neutrophils. Cell Host & Microbe 21: 611-618 e615. PMC5478421.
2. Karmakar, M., M. Katsnelson, G.R. Dubyak, and E. Pearlman. (2016) Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1ß secretion in response to ATP. Nature Communications. 15; 7:10555. PMC4756306.
3. Karmakar, M., M. Katsnelson, N.G. Greene, H. A. Malak, Scott Howell, A. G. Hise, A. Camilli, A. Kadioglu, G. R. Dubyak and E. Pearlman. (2015) Pneumolysin induces K+ efflux and NLRP3/ Caspase 1 dependent IL-1ß processing by neutrophils. J. Immunol. 194:1763-75. PMC4369676.
4. Karmakar, M., Y. Sun, A. G. Hise, A. Rietsch and E. Pearlman. 2012. Cutting Edge: IL-1ß processing during Pseudomonas aeruginosa infection is mediated by neutrophil serine proteases and is independent of NLRC4 and Caspase-1. J. Immunol. 189:4231-4235.

Pathogenesis of fungal keratitis (EY18612): was initially funded in 2008 and was renewed in 2018. Our murine studies on fungal keratitis are based on corneal ulcer material, post- transplant corneas, and peripheral blood from patients in southern India (J. Infect Dis 2015. In addition to examining the host response to pathogenic Aspergillus and Fusarium species, we identified fungal antioxidant and iron binding pathways as novel therapeutic approaches for fungal keratitis (J. Clin Invest 2012; PLoS Path 2013). Similarly, we showed that neutrophils use calprotectin (S100A8/A9) to sequester zinc and manganese, and thereby limit hyphal growth in the cornea, and that topical application of atovaquone inhibits hyphal growth in the cornea by the same mechanism (IOVS 2018). Recently, we revealed a role for CR3 rather that NETs in hyphal killing, and found an unexpected role for caspase-11 in IL-1ß processing in neutrophils in fungal keratitis.
1. Sun, Y., S. Abbondante, M. Karmakar, S. de Jesus Carrion, C. Che, A. G. Hise and E. Pearlman. 2018. Neutrophil caspase-11 is required for cleavage of caspase-1 and secretion of IL-1ß in Aspergillus fumigatus infection. Journal of Immunology. 201(9):2767-2775. PMC6200591. (Featured in In this Issue as top 10% of papers)
2. Clark, H.L., S. Abbondante, M.S. Minns, Y. Sun, E. N. Greenberg, and E. Pearlman. 2018. Protein Deiminase 4 (PAD4) and CR3 regulate Aspergillus fumigatus and ß-glucan – induced neutrophil extracellular trap formation, but hyphal killing is dependent only on CR3. Frontiers Immunol. 9:1182. PMC5986955.
3. Clark, H. L., A. Jhingran, Y. Sun, C. Vareechon, S. de Jesus Carrion, E.P. Skaar, W.J. Chazin, J.A. Calera, T.M. Hohl, and E. Pearlman. (2016) Zinc and Manganese Chelation by Neutrophil S100A8/A9 (Calprotectin) Limits Extracellular Aspergillus fumigatus Hyphal Growth and Corneal Infection. J Immunol 196, 336-44. PMC4684987 (Featured in In this Issue as top 10% of papers.)
4. Taylor, P.R., S. Roy, S.M. Leal, Jr., Y. Sun, S.J. Howell, B.A. Cobb, X. Li and E. Pearlman. (2014) Autocrine IL-17A / IL-17RC neutrophil activation in fungal infections is regulated by IL-6, IL-23, ROR? t and Dectin-2. Nature Immunology. 2: 143-151. PMC3972892.

Complete List of Published Work (120 reports, 29 reviews, 3 book chapters):
https://www.ncbi.nlm.nih.gov/pubmed?term=Pearlman%2C%20Eric%5BAuthor%5D
Grants
RO1 EY014362 Pathogenesis of Bacterial Keratitis 12/1/13 – 11/30/18
Pathogenesis of Fungal Keratitis. 03/01/08 – 12/31/23
Last updated
01/28/2019