Roman Dziarski, Ph.D.
Professor of Microbiology and Immunology
Course Director Step 6 Invasion and Defense
- University of Warsaw, Warsaw, Poland, 1971 B.Sc., Biology and
Microbiology, 1972 M.Sc., Microbiology and Genetics
- National Institute of Hygiene, Warsaw, Poland, 1977 Ph.D., Microbiology
- Professor of Microbiology and Immunology
- Course Director for Invasion and Defense
- Editorial Board, "Infection and Immunity", "Current Immunology Reviews"
- American Society for Microbiology
- Society for Leukocyte Biology
- American Association of Immunologists, FASEB
- International Endotoxin Society
Research in Dr. Dziarski's laboratory is funded by National Institutes of Health (NIH) and is focused on innate immunity to infections, which is an immediate first line of defense against infections.
In 2001, Dr. Dziarski's research group, in collaboration with Dr. Gupta's research group (both at Indiana University School of Medicine-Northwest), discovered a new family of four human genes. These genes code for molecules that were named Peptidoglycan Recognition Proteins (PGRPs), because these proteins bind to peptidoglycan, an essential component of the outer surface of all bacteria. Peptidoglycan is a target for many clinically useful antibiotics (such as penicillins, cephalosporins, and vancomycin), and Dr. Dziarski's research has now discovered that peptidoglycan is also a target for host defenses against bacterial infections. Dr. Dziarski's and Dr. Gupta's groups cloned the genes for human Peptidoglycan Recognition Proteins, purified these proteins, and recently discovered how these proteins function in antibacterial innate immunity.
Three of these Peptidoglycan Recognition Proteins directly kill bacteria and are normally produced by white blood cells, or by skin cells and surface epithelial cells on mucous membranes in the mouth, throat, intestinal tract, and in the eyes. They are also secreted into sweat, sebum, and saliva. The fourth protein is an enzyme that degrades peptidoglycan from bacteria, and thus removes this proinflammatory bacterial component from the body, which helps to limit deleterious inflammatory responses during bacterial infections. This protein is made in the liver and secreted into blood.
Dr. Dziarski's research discovered a new mechanism of anti-infectious immunity and a new class of human antibacterial proteins. These proteins can be developed into useful agents that can effectively protect people from infections with bacteria, or could be used for treatment of bacterial infections, including patients with severe immunodeficiencies. They could also be used for protection against possible bacterial agents of a bioterrorist attack. Because these proteins are naturally produced in human blood or on body surfaces, they could be safely used without a fear of allergic or toxic reactions. Future research in Dr. Dziarski's laboratory will focus on developing useful therapeutic approaches using these proteins.
Roman Dziarski, Shin Yong Park, Des Raj Kashyap, Sukumar Saha, Xuefang Jing, Fareeha Zulfiqar, Dipika Gupta
Gupta, D, Wang, Q, Vinson C, and Dziarski, R. 1999. Bacterial peptidoglycan induces CD14-dependent activation of transcription factors CREB/ATF and AP-1. Journal of Biological Chemistry, 274:14012-14020.
Schwandner, R, Dziarski, R, Wesche, H, Rothe, M, and Kirschning, CJ. 1999. Communication: Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. Journal of Biological Chemistry, 274:17406-17409.
Yoshimura, A, Lien, E, Ingalls, RR, Tuomanen, E, Dziarski, R, and Golenbock, D. 1999. Cutting Edge: Recognition of Gram-positive bacteria by the innate immune system occurs via Toll-like receptor 2. Journal of Immunology, 163:1-5.
Wang, Z-M, Liu, C, Dziarski, R. 2000. Chemokines are the main pro-inflammatory mediators in human monocytes activated by Staphylococcus aureus, peptidoglycan, and endotoxin. Journal of Biological Chemistry, 275:20260-20267.
Liu, C, Gelius, E, Liu, G, Steiner, H, and Dziarski, R. 2000. Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. Journal of Biological Chemistry, 275:24490-24499.
Dziarski, R, Viriyakosol, S, Kirkland, TN, and Gupta, D. 2000. Soluble CD14 enhances membrane CD14-mediated responses to peptidoglycan: structural requirements differ from those for responses to lipopolysaccharide. Infection and Immunity, 68:5254-5260.
Dziarski, R, Rasenick, MM, and Gupta, D. 2000. Bacterial peptidoglycan binds to tubulin. Biochimica et Biophysica Acta, 1524:17-26.
Dziarski, R, Wang, Q, Miyake, K, Kirschning, CJ, and Gupta, D. 2001. MD-2 enables Toll-like receptor-2 (TLR2)-mediated responses to LPS and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components. Journal of Immunology, 166:1938-1944.
Wang, Q, Dziarski, R, Kirschning, CJ, Muzio, M, and Gupta, D. 2001. Micrococci and peptidoglycan activate TLR2--> MyD88-->IRAK-->TRAF-->NIK-->IKK-->NF-kB signal transduction pathway that induces transcription of interleukin-8. Infection and Immunity, 69:2270-2276.
Xu, Z, Dziarski, R, Wang, Q, Swartz, K, Sakamoto, KM, and Gupta, D. 2001. Bacterial peptidoglycan-induced tnf-a transcription is mediated through the transcription factors Egr-1, Elk-1, and NF-kB. Journal of Immunology, 167:6975-6982.
Liu, C, Xu, Z, Gupta, D, and Dziarski, R. 2001. Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. Journal of Biological Chemistry, 276:34686-34694.
Doyle, RJ, and Dziarski, R. 2001. The bacterial cell: peptidoglycan. Sussman, M (ed), Molecular Medical Microbiology, Vol. 1, Chapter 7, pp. 137-154, Academic Press, London, England.
Datta, SK, Redecke, V, Prilliman, KR, Takabayashi, K, Corr, M, Tallant, T, DiDonato, J, Dziarski, R, Akira, S, Schoenberger, SP, and Raz, E. 2003. A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells. Journal of Immunology, 170:4102-4110.
Dziarski, R, Platt, KA, Gelius, E, Steiner, H, and Gupta, D. 2003. Defect in neutrophil killing and increased susceptibility to infection with non-pathogenic Gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice. Blood 102: 689-697.
Dziarski, R. 2003. Recognition of bacterial peptidoglycan by the innate immune system. Cellular and Molecular Life Sciences, 60:1793-1804.
Wang, Z-M, Li, X, Cocklin, RR, Wang, M, Wang, M, Fukase, K, Inamura, S, Kusumoto, K, Gupta, D, and Dziarski, R. 2003. Human peptidoglycan recognition protein-L (PGRP-L) is an N-acetylmuramoyl-L-alanine amidase. Journal of Biological Chemistry 278:49044-49052.
Dziarski, R. 2004. Peptidoglycan recognition proteins (PGRPs). Molecular Immunology 40:877-886.
Dziarski, R, and Gupta, D. 2005. Staphylococcus aureus peptidoglycan is a Toll-like receptor 2 activator: a reevaluation. Infection and Immunity 73:5212-5216.
Dziarski, R, and Gupta, D. 2005. Peptidoglycan recognition in innate immunity. Journal of Endotoxin Research 11:304-310.
Zhang, Y, van der Fits, L, Voerman, JS, Melief, M-J, Laman, JD, Wang, M, Wang, H, Wang, M, Li, X, Walls, CD, Gupta, D, and Dziarski, R. 2005. Identification of serum N-acetylmuramoyl-L-alanine amidase as liver peptidoglycan recognition protein 2. Biochimica et Biophysica Acta - Proteins and Proteomics 1752:34-46.
Wang, H, Gupta, D, Li, X, and Dziarski, R. 2005. Peptidoglycan recognition protein 2 (N-acetylmuramoyl-L-ala amidase) is induced in keratinocytes by bacteria through p38 kinase pathway. Infection and Immunity 73:7216-7225.
Lu, X, Wang, M, Qi, J, Wang, H, Li, X, Gupta, D, and Dziarski, R. 2006. Peptidoglycan recognition proteins are a new class of human bactericidal proteins. Journal of Biological Chemistry 281:5895-5907.
Dziarski, R. 2006. Innate immunity. Shaechter's Mechanisms of Microbial Disease, 4th Edition, Engelberg R, and DiRita V (eds), Chapter 6, pp. 66-89, Lippincott, Williams & Wilkins.
Dziarski, R, and Gupta, D. 2006. Mammalian PGRPs: novel antibacterial proteins. Cellular Microbiology 8:1056-1069.
Dziarski, R, and Gupta, D. 2006. The peptidoglycan recognition proteins (PGRPs). Genome Biology 7:232. 1-13.
Dziarski, R. 2006. Deadly plague versus mild-mannered TLR4. Nature Immunology 7: 1017-1019.
Wang, M, Liu, LH, Wang, S, Li, X, Lu, X, Gupta, D, and Dziarski, R. 2007. Human peptidoglycan recognition proteins require zinc to kill both Gram-positive and Gram-negative bacteria and are synergistic with antibacterial peptides. Journal of Immunology 178: 3116-3125.
Royet, J., and Dziarski, R. 2007. Peptidoglycan recognition proteins: pleotropic sensors and effectors of antimicrobial defenses.Nature Microbiology Reviews 5: 264-277.
Li, X, Wang, S, Qi, J, Echtenkamp, SF, Chatterjee, R, Wang, R. Boons, G-B, Dziarski, R, and Gupta, D. 2007. Zebrafish peptidoglycan recognition proteins are bactericidal amidases essential for defense against bacterial infections. Immunity 27, 518-528.
Saha, S., Qi, J., Wang, S. Wang, M, Li, X. Kim, Y-G., Núñez, G., Gupta, D., and Dziarski, R. 2009. PGLYRP-2 and Nod2 ae both required for peptidoglycen-induced artihritis and local inflammation. Cell Host & Microbe 5: 137-150.
Saha, S, Jing, X, Park, SY, Wang, S, Li, X, Gupta, D, and Dziarski, R. 2010. Peptidoglycan Recognition Proteins protect mice from experimental colitis by promoting normal gut flora and preventing induction of interferon-g. Cell Host & Microbe 8:147-162.
Kashyap, DR, Wang, M, Liu, LH, Boons, GJ, Gupta D, and Dziarski, R. 2011. Peptidoglycan recognition proteins kill bacteria by activating protein-sensing two-component systems. Nature Medicine 17:676-683.
Park, SY, Gupta, D, Kim, CH, and Dziarski, R. 2011. Differential effects of peptidoglycan recognition proteins on experimental atopic and contact dermatitis mediated by Treg and Th17 cells. PLoS One 6: e24961. p. 1-16.
Park, SY, Gupta, D, Hurwich, R, Kim, CH, and Dziarski, R. 2011. Peptidoglycan recognition protein Pglyrp2 protects mice from psoriasis-like skin inflammation by promoting regulatory T cells and limiting Th17 responses. Journal of Immunology 187: 5813-5823.
Royet, J, Gupta, D, and Dziarski, R. 2011. Peptidoglycan recognition proteins: modulators of the microbiome and inflammation. Nature Reviews Immunology 11:837-851.