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BIOGRAPHICAL SKETCH NAME POSITION TITLE Patricia R Taylor, Ph.D. Instructor COMMONS ID PATTYT1024 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION YEAR(s) FIELD OF STUDY (if applicable) University of Akron, Ohio B.S. 2005 Microbiology University of Akron, Ohio M.S. 2007 Biology Kent State University, Ohio Ph.D. 2010 Biomedical Sciences Case Western Reserve University, Ohio Post-doctoral 2010-14 Ocular Immunology A. Personal Statement The goal of the proposed research is to characterize the role of IL-17 lymphocytes and neutrophils in retinal pathology during diabetic retinopathy. Through this research I postulate that potential IL-17 immunomodulators will the delay onset of retinal pathology, which can be used as future therapeutics. My training has been in multiple areas of immunology, but the past few years I have focused on the characterization of a novel subset of IL-17 producing neutrophils, which was recently published in Nature Immunology. Over the past year, I have expanded my ocular immunology background to examine the role of IL-17 producing neutrophils in diabetic retinopathy. Early studies in animal models suggest that diabetes mediates IL-17 production in both lymphocytes and neutrophils, which induce retinal pathogenesis in early stage diabetic retinopathy. As a new junior faculty member of the Department of Ophthalmology at Case Western Reserve University’s School of Medicine, I am collaborating with a team of well-established ophthalmologists and vision science researchers that are helping me characterize this diabetes-mediated immune dysfunction that is eliciting IL-17-driven pathology. Since this is the first study of IL-17 producing neutrophils in diabetes, these novel discoveries should lead to potential therapeutics for multiple diabetes complications. B. Positions and Honors OCCUPATION BEG DATE (mm/yy) ENDING DATE (mm/yy) Post-doctoral Fellow Instructor 09/10 08/14 08/14 Present FIELD Immunology Immunology Academic and Professional Honors 2013-2015 NIH LRP Extramural Clinical Research Award 2010 FOCIS Travel Award 2005 Magna cum Laude 2003-2004 McLaughlin Academic Scholarship 2004 Phi Sigma Alpha Scholastic Achievement 2003 Golden Key International Honor Society Award 2002 Mortar Board National College Senior Honor Society Award 2001 National Society of Collegiate Scholars Award 2001 Phi Theta Kappa Honor Society Award INSTITUTION/ COMPANY CWRU CWRU SUPERVISOR/ EMPLOYER Eric Pearlman, PhD Douglas Rhee, MD C. Contributions to Science My major contributions to science are in the field of cellular and ocular immunology, focusing on characterizing and immunomodulating innate immune cells. My neutrophil study published in Nature Immunology (2014) has been my highest impact work. In this paper, I characterized a novel subset of neutrophils that both produce and respond to IL-17, which makes this neutrophil the first autocrine IL-17 cell discovered. This IL-17 autocrine activity is important because it elicits increased production of reactive oxygen species and proteinases, which is very relevant to tissue damage in multiple infectious diseases, and autoimmune and chronic disorders; including diabetic retinopathy. 1. Modulation of innate immune cells. During my graduate studies, my research focused on identifying immune-mediated mechanisms that regulated the adaptive immune response against HSV-1 and HIV, using a ligand-epitope antigen presenting system. This included the identification of one of the first viral dendritic cell vaccines. During my pre-doctoral studies, my mentors and I successfully designed a method for modulating immunogenic responses by activating dendritic cells for immune interventions in multiple viral infections (Patent PCT/US2010/031054). a. Rosenthal KS, Taylor PR, Zimmerman DH. 2012. J-LEAPS Peptide and LEAPS-Dendritic Cell Vaccines. 2011. Microbial Biotechnology 5(2): 203-13. PMCID: PMC3815780. b. Taylor PR, Koski GK, Paustian CC, Bailey E, Moore FBG, Cohen PA, Zimmerman DH, Rosenthal KS. 2010. J-LEAPS Vaccines Initiate Murine Th1 Responses by Activating Dendritic Cells. Vaccine 28(34): 5533-42. PMID: 20600501. c. Taylor PR, Paustian CC, Koski GK, Zimmerman DH, Rosenthal KS. 2010. Maturation of dendritic cell precursors into IL12 producing DCs by J-LEAPS Immunogens. Cellular Immunology 262:1-5. PMID: 20163792. d. Zimmerman DH, Taylor P, Talor E, Bendele A, O’Neill S, Rosenthal KS. 2010. CEL-2000 Therapeutic Vaccine Arrests Disease Progression in Collagen Type II Model for Rheumatoid Arthritis. International Immunopharmacology 10(4): 412-21. PMID: 20074669. 2. Characterization of IL-17 activation mechanisms in immune cells. In my collaborative studies, I assisted in the mechanistic characterization of innate cell activation of IL17 producing lymphocytes. a. Deng Z, Ma S, Zhou H, Zang A, Fang Y, Li T, Shi H, Liu M, Du M, Taylor PR, Zhu HH, Chen J, Meng G, Li F, Chen C, Zhang Y, Jia XM, Lin X, Zhang X, Pearlman E, Li A, Feng GS, Xiao H. 2015. Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal TH17 responses. Nature Immunology 16: 642-652. PMCID: PMC4439382. b. Paustian C, Taylor P, Johnson T, Xu M, Rosenthal KS, Shu S, Cohen PA, Czerniecki BJ, Koski G. 2013. Extracellular ATP and Toll-like Receptor Agonists Trigger Human Monocytes and Activation Program that Favors T helper 17. PLoS ONE 8(1): e54804. PMCID: PMC3561418. 3. Discovery of a novel IL-17 producing neutrophil subset. My post-doctoral project focused on the innate and adaptive immune response during cornea infections, which led to the discovery and characterization of a novel neutrophil population. I determined that this neutrophil population both produces and responds to IL-17, which is the first IL-17 autocrine cell discovered. These discoveries are directly relevant to all of my current studies. a. Taylor PR, Roy S, Meszaros EC, Sun Y, Howell SJ, Malemud CJ, Pearlman E. 2016. JAK/STAT regulation of Aspergillus fumigatus corneal infections and IL-6/23-stimulated neutrophil. IL-17, elastase, and MMP9 activity. Journal Leukocyte Biology 100(1): 213-222. PMCID: PMC4946614. b. Taylor PR, Pearlman E. 2015. IL-17A production by neutrophils. Immunology Letters 169: 104-5. PMID: 26582721. c. Taylor PR, Roy S, Leal SM Jr, Sun Y, Howell SJ, Cobb BA, Li X, Pearlman E. 2014. Autocrine IL17A / IL-17RC neutrophil activation in fungal infections is regulated by IL-6, IL-23, RORγ t and Dectin-2. Nature Immunology 2:143-151. PMCID: PMC3972892. d. Taylor PR, Leal SM Jr, Sun Y, Pearlman E. 2014. Aspergillus and Fusarium corneal infections are regulated by Th17 cells and IL-17 producing neutrophils. Journal Immunology 192:3319-27. PMCID: PMC4020181. e. Sun Y, Karmakar M, Taylor PR, Rietsch A, Pearlman E. 2012. ExoS and ExoT ADPribosyltransferase activities mediate Pseudomonas aeruginosa keratitis by promoting neutrophil apoptosis and bacterial survival. Journal of Immunology 188(4): 1884-95. PMCID: PMC3273577. 4. Identification of IL-17 producing neutrophils in multiple disease states. Currently, I am investigating the role of IL-17 producing neutrophils in autoimmune disease, chronic inflammatory disease, and in microbial infections. My collaborators and I have determined that IL-17 producing neutrophils have a pathologic role in fungal keratitis, Pseudomonas keratitis, diabetic retinopathy, and cystic fibrosis. These discoveries are directly relevant to all of my current studies. a. Taylor PR, Bonfield TL, Chmiel JF, Pearlman E. 2016. Neutrophils from F508del cystic fibrosis patients produce IL-17A and express IL-23-dependent IL-17RC. Journal Clinical Immunology 170:53-60. PMID: 2715536. b. Hsu D, Taylor P, Fletcher D, van Heekeren R, Eastman J, van Heekeren A, Davis P, Chmiel J, Pearlman E, Bonfield T. 2016. Interleukin-17 pathophysiology and therapeutic intervention in cystic fibrosis lung infection and inflammation. Infection and Immunity 84(9):2410-2421. PMCID: PMC4995906. D. My Bibliography 1. Taylor PR, Bonfield TL, Chmiel JF, Pearlman E. 2016. Neutrophils from F508del cystic fibrosis patients produce IL-17A and express IL-23-dependent IL-17RC. Journal Clinical Immunology 170:5360. PMID: 2715536. 2. Hsu D, Taylor P, Fletcher D, van Heekeren R, Eastman J, van Heekeren A, Davis P, Chmiel J, Pearlman E, Bonfield T. 2016. Interleukin-17 pathophysiology and therapeutic intervention in cystic fibrosis lung infection and inflammation. Infection and Immunity 84(9):2410-2421. PMCID: PMC4995906. 3. Taylor PR, Roy S, Meszaros EC, Sun Y, Howell SJ, Malemud CJ, Pearlman E. 2016. JAK/STAT regulation of Aspergillus fumigatus corneal infections and IL-6/23-stimulated neutrophil. IL-17, elastase, and MMP9 activity. Journal Leukocyte Biology 100(1): 213-222. PMCID: PMC4946614. 4. Deng Z, Ma S, Zhou H, Zang A, Fang Y, Li T, Shi H, Liu M, Du M, Taylor PR, Zhu HH, Chen J, Meng G, Li F, Chen C, Zhang Y, Jia XM, Lin X, Zhang X, Pearlman E, Li A, Feng GS, Xiao H. 2015. Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal TH17 responses. Nature Immunology 16: 642-652. PMCID: PMC4439382. 5. Taylor PR, Pearlman E. 2015. IL-17A production by neutrophils. Immunology Letters 169: 104-5. PMID: 26582721. 6. Taylor PR, Roy S, Leal SM Jr, Sun Y, Howell SJ, Cobb BA, Li X, Pearlman E. 2014. Autocrine IL17A / IL-17RC neutrophil activation in fungal infections is regulated by IL-6, IL-23, RORγ t and Dectin-2. Nature Immunology 2:143-151. PMCID: PMC3972892. 7. Taylor PR, Leal SM Jr, Sun Y, Pearlman E. 2014. Aspergillus and Fusarium corneal infections are regulated by Th17 cells and IL-17 producing neutrophils. Journal Immunology 192:3319-27. PMCID: PMC4020181. 8. Paustian C, Taylor P, Johnson T, Xu M, Rosenthal KS, Shu S, Cohen PA, Czerniecki BJ, Koski G. 2013. Extracellular ATP and Toll-like Receptor Agonists Trigger Human Monocytes and Activation Program that Favors T helper 17. PLoS ONE 8(1): e54804. PMCID: PMC3561418. 9. Sun Y, Karmakar M, Taylor PR, Rietsch A, Pearlman E. 2012. ExoS and ExoT ADPribosyltransferase activities mediate Pseudomonas aeruginosa keratitis by promoting neutrophil apoptosis and bacterial survival. Journal Immunology 188(4): 1884-95. PMCID: PMC3273577. 10. Rosenthal KS, Taylor PR, Zimmerman DH. 2012. J-LEAPS Peptide and LEAPS-Dendritic Cell Vaccines. Microbial Biotechnology 5(2): 203-13. PMCID: PMC3815780. 11. Taylor PR, Koski GK, Paustian CC, Bailey E, Moore FBG, Cohen PA, Zimmerman DH, Rosenthal KS. 2010. J-LEAPS Vaccines Initiate Murine Th1 Responses by Activating Dendritic Cells. Vaccine 28(34): 5533-42. PMID: 20600501. 12. Taylor PR, Paustian CC, Koski GK, Zimmerman DH, Rosenthal KS. 2010. Maturation of dendritic cell precursors into IL12 producing DCs by J-LEAPS Immunogens. Cellular Immunology 262:1-5. PMID: 20163792. 13. Zimmerman DH, Taylor P, Talor E, Bendele A, O’Neill S, Rosenthal KS. 2010. CEL-2000 Therapeutic Vaccine Arrests Disease Progression in Collagen Type II Model for Rheumatoid Arthritis. International Immunopharmacology 10(4): 412-21. PMID: 20074669. E. Research Support Completed Research Support RO1 EY018612 01/01/15 – 04/30/16 Title: Pathogenesis of Fungal Keratitis Role: co-I (subcontract) Agency: National Eye Institute Description: This project examines the activation mechanism of IL-17 producing neutrophils during fungal corneal infections to identify potential therapeutic targets. F32 EY022278 08/01/12 – 08/01/14 Title: The role of IL-17 in fungal keratitis Role: PI Agency: National Eye Institute Description: This project examined the role of IL-17 producing neutrophils and Th17 cells in Fusarium and Aspergillus keratitis, using a murine model of fungal keratitis. T32 EY07157 10/01/10 – 02/01/12 Title: Adaptive immunity during Aspergillus keratitis Role: Post-doctoral Trainee (Visual Sciences Training Program) Agency: National Eye Institute Description: The goals of this training grant was to design an immunized murine model that induced an adaptive immune response to a fungal cornea infection, under the mentorship of Dr. Eric Pearlman. Current Research Support VA-K2 BX003403 04/01/16 – 03/31/21 Title: The role of IL-17 neutrophils and lymphocytes during diabetic retinopathy Role: PI Agency: Biomedical Laboratory Research & Development-Neurology F Description: This project examines the role of IL-17 in diabetic retinopathy and examines potential therapeutic targets that would delay the onset of clinical retinopathy.