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

Irvine, CA 92697

picture of Eric  Pearlman

Research
Interests
Innate immunity, bacterial infections, fungal infections, neutrophils, cornea,
   
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 has focused on host defense mechanisms in response to parasitic, fungal and bacterial infections, which has been funded by the NIH for over 20 years. The focus of this research has been innate immunity and pathogen recognition receptors, especially the role of neutrophils. In one area of research, we are building on our findings that human neutrophils express IL-17A and a functional IL-17RA/RC receptor, leading to autocrine IL-17 activation (Nature Immunology 2014). We also discovered that IL-17 producing neutrophils cells are prominent in the lungs of cystic fibrosis patients undergoing pulmonary exacerbations, and are associated with elevated levels of proteases that may contribute directly to pathology.
An additional area of interest is the role of neutrophils as a primary source of mature IL-1ß at the early stage of bacterial infection. We demonstrated that neutrophils activate the NLRP3 inflammasome in response to Streptococcus pneumoniae and release of pneumolysin (J Immunol. 2015. More recently, we demonstrated that IL-1ß is activated ATP through the P2X7 receptor (Nature Communications, 2016), and identified a key mechanism by which Pseudomonas aeruginosa survives in human neutrophils (Cell Host and Microbe, 2017).
   
Publications 1. Host response in Cystic Fibrosis
Our recent interest in cystic fibrosis focused on characterizing neutrophils in the sputum of cystic fibrosis patients, and using murine models.
a. Taylor, P. R., T. L. Bonfield, J. F. Chmiel, and E. Pearlman. 2016. Neutrophils from F508del cystic fibrosis patients produce IL-17A and express IL-23 - dependent IL-17RC. Clin Immunol 170: 53-60. PMID:27155366.
b. Hsu, D., P. Taylor, D. Fletcher, R. van Heeckeren, J. Eastman, A. van Heeckeren, P. Davis, J. F. Chmiel, E. Pearlman, and T. L. Bonfield. 2016. Interleukin-17 Pathophysiology and Therapeutic Intervention in Cystic Fibrosis Lung Infection and Inflammation. Infect Immun 84: 2410-24. PMID:27271746.

2. Fungal Infections of the Cornea
Our murine studies on fungal keratitis are based on characterization of corneal ulcer material, post-transplant corneas, and peripheral blood from patients at the Aravind Eye Hospital in India. Indeed, the 2011 J Infect Dis paper noted elevated Il17a gene expression in corneal ulcers when neutrophils comprised >90% cells present, leading us to examine this pathway. In addition to examining the host response to pathogenic Aspergillus and Fusarium species, we have also identified fungal antioxidant and iron binding pathways as novel therapeutic approaches for fungal keratitis.
a. Clark, H. L. and E. Pearlman. 2017. Fungal Eye Infections. In: Oxford Textbook of Medical Mycology. Editors: Kibbler, Barton, Gow, Howell, Maccallum and Manuel. In press.
b. Clark, H. L., Jhingran, A., Sun, Y., Vareechon, C., de Jesus Carrion, S., Skaar, E. P., Chazin, W. J., Calera, J. A., Hohl, T. M., Pearlman, E. (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.
c. Taylor, P. R., S. Roy, E. C. Meszaros, Y. Sun, S. J. Howell, C. J. Malemud, and E. Pearlman. 2016. JAK/STAT regulation of Aspergillus fumigatus corneal infections and IL-6/23 - stimulated neutrophil elastase and MMP-9 activity. J. Leuk. Biol. 100: 213-222
d. Karthikeyan RS, Vareechon C, Prajna NV, Dharmalingam K, Pearlman E, Lalitha P. 2015. IL-17 expression in peripheral blood neutrophils from fungal keratitis patients and healthy cohorts in south India. J Infect Dis. 211(1):130-4. PMC25001461.
e. 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
f. Taylor, P. R., S. M. Leal, Jr., Y. Sun, and E. Pearlman. 2014. Aspergillus and Fusarium corneal infections are regulated by Th17 cells and IL-17 producing neutrophils. J. Immunol. 192:3319-27. PMC4020181.
g. Leal, S.M. Jr., S. Roy, C. Vareechon, H. Clark, S. de Jesus Carrion, M. S. Lopez-Berges, A. diPietro, M. Schrettl, N. Beckman, B. Redl, H. Haas and E. Pearlman. 2013. Targeting iron acquisition blocks infection with the fungal pathogens Aspergillus fumigatus and Fusarium oxysporum. PLoS Pathogens. 9:e1003436. PMC3708856.
h. Leal, S. M. J., C. Vareechon, S. Cowden, B. A. Cobb, J.-P. Latge, M. Momany, and E. Pearlman. 2012. Fungal antioxidant pathways promote survival against neutrophils during infection. J Clin Invest. 122:2482-2498. PMC3534057.

3. Bacterial infections of the cornea
Our studies identified major pathogen recognition receptors and signaling pathways essential for an effective innate immune response to Pseudomonas aeruginosa and Streptococcus pneumoniae. These studies also identified essential bacterial virulence factors required for growth in the cornea, and demonstrate their primary functions. We definitively showed that neutrophils are a major source of the pro-inflammatory cytokine IL-1ß during infection, cleaving the pro-form of this cytokine either by caspase-1-dependent or –independent pathways. We also reported that the purinergic P2X7 receptor is expressed and functional on human and murine neutrophils, and is required for production of IL-1ß. Neutrophil P2X7R receptor is also an essential player in corneal infection. In collaboratoin with Arne Rietsch, we identified a key mechanism by which P. aeruginosa survives in human neutrophils.
a. Vareechon C, Zmina SE, Karmakar M, Pearlman E, Rietsch A. Pseudomonas aeruginosa Effector ExoS Inhibits ROS Production in Human Neutrophils. Cell Host Microbe 2017;21:611-618 e615. PMID:28494242
b. Karmakar, M., Katzenelson M., Dubyak, G. R., Pearlman, E. (2016) Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1ß secretion in response to ATP. Nature Communications. 15;7:10555. PMC4756306.
c. 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.
d. Roy, S., M. Karmakar and E. Pearlman. 2013. CD14 Mediates Toll-like Receptor 4 (TLR4) Endocytosis and Spleen Tyrosine Kinase (Syk) and Interferon Regulatory Transcription Factor 3 (IRF3) Activation in Epithelial Cells and Impairs Neutrophil Infiltration and Pseudomonas aeruginosa Killing in Vivo. J. Biol Chem. 289(2):1174-82. PMC3887184.
e. Karthikeyan, R.S., JL Priya, S.M. Leal, Jr., V. Prajna, K. Dharmalingam, A. Rietsch, E. Pearlman and L. Prajna. 2013. Host response gene and bacterial virulence factor expression in human corneas infected with Pseudomonas aeruginosa or Streptococcus pneumoniae. PLoS One. Jun 4;8(6):e64867.
f. Karmakar, M., Y. Sun, A.G. Hise, A. Rietsch and E. Pearlman. 2012. IL-1ß processing during Pseudomonas aeruginosa infection is mediated by neutrophil serine proteases and is independent of NLRC4 and Caspase-1. J Immunol Cutting Edge. 189:4231-4235. PMC3482477.

Complete List of Published Work: http://www.ncbi.nlm.nih.gov/pubmed/?term=pearlman+neutrophils
   
Grants RO1EY018612 Pathogenesis of Fungal Keratitis 3/1/2008 – 4/30/17
   
RO1 EY014362 Pathogenesis of Bacterial Keratitis 12/1/13 – 11/30/18
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=6124
   
Last updated 06/13/2017