Jonathan S. ReichnerCo-Director of the Pathobiology Graduate Program, Professor of Surgery (Research)
Dr. Reichner is a Professor in the Department of Surgery at the Brown University Medical School, Providence, RI. He received his BS from the Ohio State University in 1976 and worked as a clinical microbiologist until entering graduate school. He received his Ph.D. in Microbiology and Immunology from the State University of New York at Buffalo in 1983. He completed postdoctoral work at MD Anderson Hospital & Tumor Institute of the University of Texas Cancer Center and the Johns Hopkins School of Medicine.
Johnson, C.M., O’Brien, X.M., Byrd, A.S., Parisi, V.E., Loosely, A.J., Li., W., Witt, H., Faridi, M.H., Lefort, C.T., Gupta, V., Kim, M., and Reichner, J.S. Integrin cross-talk regulates the human neutrophil response to fungal beta-glucan in the context of extracellular matrix: A prominent role for VLA3 in the anti-fungal response. J. Immunology 198:318-334, 2017
O’Brien, X.M., Biron, B.M. and Reichner, J.S. Consequences of extracellular trap formation in sepsis. Curr. Opin. Hemat., 24:66-71, 2017
Byrd, A.S., O’Brien, X.M., Laforce-Nesbitt, S.S., Parisi, V., Hirakawa, M.P., Bliss, J.M. and Reichner, J.S. NETosis in neonates: evidence of a ROS-independent pathway in response to fungal challenge. J. Infectious Diseases, 213:634-639, 2016.
Stout, D.A., Bar-Kochba, E., Estrada, J.B., Toyjanova, J., Kesari, H., Reichner, J.S. and Franck, C. Mean deformation metrics for quantifying 3D cell-matrix interactions in the absence of material properties. PNAS, 113:2898-2903, 2016. PMID: 26929377
Biron, B.M, Chung, C.S., O’Brien, X.M., Chen, Y., Reichner, J.S. and Ayala, A. Cl-amidine prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival, in a murine sepsis model. J. Innate Immunity, (epub ahead of press), 2016.
O’Brien, X.M. and Reichner, J.S. Neutrophil integrins and matrix ligands and NET release. Front. Immunol, 7:363-366, 2016.
Toyjanova, J., Flores, E., Reichner, J.S. and Franck, C. Matrix confinement plays a pivotal role in regulating neutrophil-generated tractions, speed and integrin utilization. J. Biol. Chem. 290:3752-3763, 2015.
Loosely, A., O’Brien, X., Reichner, J.S., and Tang, J.X. Describing Directional Cell Migration with a Characteristic Directionality Time. PLOS One, 10:e0127425, 2015
Ayala, A., Elphick, G.F., Kim, Y.S., Huang, X., Carreira-Rosario, A., Santos, S.C., Shubin, N.J., Chen Y., Reichner, J.S, Chung, C.S.Sepsis-Induced Potentiation of Peritoneal Macrophage Migration Is Mitigated by Programmed Cell Death Receptor-1 Gene Deficiency. J. Innate Immunity, 6:325-338, 2014.
O’Brien, X.M., Heflin, K.E., Loosley, A., Tang, J.X. and Reichner, J.S. Introducing a Novel Metric, Directionality Time, to Quantify Human Neutrophil Chemotaxis as a Function of Matrix Composition and Stiffness. J. Leuk. Biol, 95:993-1004, 2014.
Toyjanova, J., Bar-Kochba, E., Lopez-Fagundo, C., Reichner, J.S., Hoffman-Kim, D. and Franck, C. High resolution, large deformation traction force microscopy. PLOS One, 9:e90976, 2014.
Magruder, H.T, Quinn, J.A, Schwartzbauer, J.E., Reichner, J.S, Huang, A and Filardo, E.J. The G-protein-coupled estrogen receptor, GPER-1, promotes fibrillogenesis via a Shc-dependent pathway resulting in anchorage-independent growth. Hormones and Cancer 5:390-404, 2014.
Byrd, A.S., O'Brien, X.M., Johnson, C.M., Lavigne, L.M. and Reichner, J.S. An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to C. albicans. J. Immunology 190:4136-4148, 2013.
Brancato, S.K., Thomay, A.A., Daley, J.M., Crane, M.J. Reichner, J.S., Sabo, E. and Albina, J.E. Toll-like receptor 4 signaling regulates the acute local inflammatory response to injury and the fibrosis/neovascularization of sterile wounds. Wound Repair Regen. 21: 2013.
Fox, E., Heffernan, D., Cioffi, W., and Reichner, J.S. Neutrophils from critically ill patients mediate profound loss of barrier integrity. Critical Care. 17:226-232, 2013.
O'Brien XM, Heflin KE, Lavigne LM, Yu K, Kim M, Salomon AR, Reichner JS. Lectin site ligation of CR3 induces conformational changes and signaling. J Biol Chem. 287:3337-3348, 2012
Newsome CT, Flores E, Ayala A, Gregory S, Reichner J.S. Improved antimicrobial host defense in mice following poly-(1,6)-β-D-glucopyranosyl-(1,3)-β-D-glucopyranose glucan treatment by a gender-dependent immune mechanism. Clin Vaccine Immunol. 18:2043-9, 2011
Daley, J.M., Brancato, S.K., Thomay, A.A., Reichner, J.S. and Albina, J.E. The phenotype of the wound macrophage. J. Leuk. Biol. 87:1, 2010.
Oakes, P.W., Morin, N.A., Zitterbart, D.P., Patel, D. C., Fabry, B., Reichner, J.S. (Corresponding author), and Tang J.X. Neutrophil morphology and migration are affected by substrate elasticity. Blood, 114:1387-1395, 2009.
Elphick, G.F., Sarangi, P.P., Hyun, Y-M, Hollenbaugh, J.A., Ayala, A., Biffl, W.L., Chung, H-L., Rezaie, A.R., McGrath, J.L., Topham, D.J., Reichner, J.S. and Kim, M. Recombinant human activated protein C inhibits integrin-mediated neutrophil function. Blood, 113:4078-4085
Muratore, C.S., Luks, F.I., Zhou, Y., Harty, M., Reichner, J., and Tracy, T.F. Endotoxin alters early fetal lung morphogenesis. J. Surg. Res. 155:225-230, 2009.
Morin NA, Oakes PW, Hyun YM, Lee D, Chin YE, King MR, Springer TA, Shimaoka M, Tang JX, Reichner JS, Kim M. Abstract Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J Exp Med. 2008 Jan 21;205(1):195-205.
Lavigne LM, O'Brien XM, Kim M, Janowski JW, Albina JE, Reichner JS. Integrin engagement mediates the human polymorphonuclear leukocyte response to a fungal pathogen-associated molecular pattern. J Immunol. 2007 Jun 1;178(11):7276-82.
LeBlanc, B.W., Albina, J.E. and Reichner, J.S. Effect of beta-glucan on neutrophil chemotaxis in vivo. Journal Leukocyte Biol. 79:667-675, 2006.
Lavigne LM, Albina JE, Reichner JS. beta-Glucan Is a Fungal Determinant for Adhesion-Dependent Human Neutrophil Functions. J Immunol. 177:8667-75, 2006.
Daley, J.M., Reichner, J.S., Mahoney, E.J., Manfield, L., Henry Jr., W.L., Mastrofrancesco, B., and Albina, J.E. The anti-inflammatory neutrophil: Wound neutrophils suppress macrophage TNF-alpha release. J. Immunol. 174:2265-2272, 2005.
Albina, J.E., Mahoney, E.J., Daley, J.M., Wesche, D.E, Morris, S.M., and Reichner, J.S. Macrophage arginase I regulation by C/EBPß. SHOCK 23:168-172, 2005.
Tsikitis, V., Morin, N., Harrington, E., Albina, J.E. and Reichner, J.S. Glucan protects the integrity of an endothelial monolayer in the presence of activated neutrophils. J. Immunol. 173:1284-1291, 2004.
Tsikitis, V.L., Albina, J.E., and Reichner, J.S. ß-glucan affects leukocyte navigation in complex chemotactic gradients. Surgery 136:384-389, 2004.
Ivanov, S.S., Chung, A.S., Yuan, P.Z., Guan, A.Y., Sachs, K.V., Reichner, J.S. and Chin, Y.E. Antibodies immobilized as arrays to profile protein post-translational modifications in mammalian cells. Molecular and Cellular Proteomics 3:788-795, 2004
ß-glucan is a (1,3)(1,6)-beta-linked polymer of glucose normally found as a structural component of the fungal cell wall. Since beta-glucan is not expressed in mammalian cells, it is an example of a pathogen-associated molecular pattern (PAMP) that permits leukocytes to recognize microbes as foreign. Although PAMPs are now understood to be a significant aspect of nonself recognition, mechanisms that regulate the subsequent host response to these molecules are not well understood. When purified and injected in soluble form, ß-glucan has been shown to prime the innate immune system without cytokine production. Experimental animals receiving ß-glucan showed improved outcomes when challenged with pathogens or tumors.
Neutrophils are capable of recognizing linear polymers of glucose linked in ß-1,3 conformation (viz., ß-glucan) which is a cell wall component of infectious microorganisms including yeast, fungi and bacteria. The recognition of ß-glucan by these cells is of benefit to host defense in two ways: first, since glucose does not occur in mature mammalian glycoproteins, ß-glucan provides a recognition mechanism through which neutrophils can bind and clear microorganisms without the need for opsonization; and second, ß-glucan binding stimulates neutrophil functions including chemotaxis, phagocytosis and oxidative burst. However, the mechanism(s) by which these inflammatory cells recognize ß-glucan is not defined. Work in this laboratory suggests that human neutrophils detect ß-glucan through novel interactions with cell surface integrins producing subsequent effects on cell motility. Ongoing efforts are directed at defining the mechanism(s) of this recognition and the second messenger signalling events that are triggered within the migrating cell. This work entails microscopic techniques in cell migration and immunocytochemistry, as well as protein biochemistry and molecular biology to investigate intracellular signalling pathways.
Translational Research: Although the innate immune system has been studied for a number of years, a well-defined pharmacological intervention to beneficially prime the function of neutrophils or macrophages is still lacking. This is so because the favorable aspects of cell priming needed to improve host defense is often accompanied by the overproduction of proinflammatory mediators at levels that cannot be tolerated by human subjects. PGG-ß-glucan, a soluble form of ß-glucan extracted from Saccharomyces cerevsiae, has been shown to prime leukocyte functions while not eliciting cytokine production in experimental animals and in high-risk surgical patients. It is this desirable property of PGG-ß-glucan that allowed for its evaluation in clinical trials where it was well tolerated by patients participating in phase III studies at the doses used in this report and underlies its therapeutic potential as an immunomodulator. Therapeutic opportunities in improving host response to cancer and infectious disease are being pursued by Biothera, Eagan, MN
Michael Harman, Ph.D., postdoctoral fellow
Hadley Witt, MA, graduate student
2014 –2019 “Neutrophil-Endothelial Interactions and Barrier Function in Sepsis”
Multi-PI: M. Kim, J. Reichner, R. Waugh
2015-2020 “Use of Biomimicry to Determine the Effect of Sepsis on Neutrophil Traction”