Director, Institute for Immunology, Physiology & Biophysics
|Innate immunity, bacterial infections, fungal infections, neutrophils, cornea,|
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
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
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 discover 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. This study has been submitted for publication: Neutrophils from F508del cystic fibrosis patients produce IL-17A and express IL-23 - dependent IL-17RC.
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. In collaboration with Dr. George Dubyak at CWRU, 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, In Press.)
Innate immunity (Toll Like Receptors) and bacterial infections:
1. Karmakar, M., A., K. M., Dubyak, G. R., Pearlman, E. (2016) Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1ß secretion in response to ATP. Nature Communications. In Press.
2. 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(4):1763-75. PMID: 25609842
3. 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.
4. Karthikeyan, R.S., JL Priya, S.M. Leal, Jr., V. Prajna, K. Dharmalingam, A. Rietsch, E. Pearlman and P. Lalitha. 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. PMC3672173.
5. 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.
6. Sun, Y., P. Taylor, A. Rietsch and E. Pearlman. 2012. Effectors ExoS and ExoT synergize to promote Pseudomonas aeruginosa corneal infections. J. Immunol. 188(4):1884-95. PMC3273577
7. Roy, S., Y. Sun and E. Pearlman. 2011. IFN- ? - induced MD-2 expression and LPS responsiveness in corneal epithelial cells is mediated by JAK2 activation and direct binding of STAT1 to the MD-2 promoter. J. Biol. Chem. 286. 23753-62. PMC3129156.
Innate immunity to pathogenic fungi:
1. 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.
2. Underhill, D. M. and Pearlman, E. (2015) Immune Interactions with Pathogenic and Commensal Fungi: A Two-Way Street. Immunity 43, 845-58.
3. 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.
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.
5. 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
6. Carrion, SDJ, S. M. Leal Jr., M.A. Ghannoum and E. Pearlman. 2013. Hydrophobin RodA protein is essential for masking the host immune response and enhancing fungal survival of Aspergillus fumigatus during corneal infection. J. Immunol. 191(5):2581-8. PMC4020118.
7. 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.
8. 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.
Complete List of Published Work: http://www.ncbi.nlm.nih.gov/pubmed
|Grants||RO1EY018612 Pathogenesis of Fungal Keratitis 3/1/2008 – 4/30/17|
|RO1 EY014362 Pathogenesis of Bacterial Keratitis 12/1/13 – 11/30/18|
|R21EY024817 Innovative therapeutic targets for fungal keratitis 10/1/14 – 9/30/16|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=6124|