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 Department of Defense (DoD), and is focused on innate immunity, 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 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 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 and respiratory tracts, 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 (PGRPs) kill bacteria indirectly, by inducing a misguided defense response in bacteria that results in metabolic, oxidative, thiol, and metal stress and becomes lethal for bacterial cells. This principle of lethal stress induction in bacteria can be developed into useful agents that can effectively protect people from infections with bacteria, or could be used for treatment of bacterial infections with antibiotic-resistant bacteria, including infections in patients with immunodeficiencies.
Peptidoglycan Recognition Proteins also play a role in maintaining the proper healthy composition of the microbiome, which is the entire community of microorganisms that live in or on the body, for example in the intestinal tract, or on the skin and mucous membranes. Microbiome provides the host with essential nutrients (such as vitamins), helps to break down indigestible compounds (such as complex carbohydrates), defends the host against infections with pathogens, and also is required for the proper development and function of the immune system and metabolism. Changes in microbiome predispose the host to various diseases, such as inflammatory bowel disease, obesity, diabetes, arthritis, and asthma. Thus, PGRPs play a role in protecting the host from several diseases by helping to maintain the healthy microbiome.
The current research in Dr. Dziarski's laboratory is focused on unraveling all the biochemical steps in PGRP-induced bacterial killing with a long-term goal of finding new targets and approaches to developing novel preventive and therapeutic measures for infections with antibiotic-resistant bacteria. Another line of research aims to determine how the control of microbiome by PGRPs can be used to protect the host from inflammatory and metabolic diseases.
Roman Dziarski, Shin Yong Park, Des Raj Kashyap, Sukumar Saha, Xuefang Jing, Fareeha Zulfiqar, Dipika Gupta
Liu C, Gelius E, Liu G, Steiner H, Dziarski R. 2000. Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. J. Biol. Chem. 275: 24490-24499, PMID: 10827080.
Liu C, Xu Z, Gupta D, Dziarski R. 2001. Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. J. Biol. Chem. 276: 34686-34694 (featured on the cover), PMID: 11461926.
Dziarski R, Platt KA, Gelius E, Steiner H, 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 (featured in a Blood editorial), PMID: 12649138.
Wang Z-M, Li X, Cocklin RR, Wang M, Wang M, Fukase K, Inamura S, Kusumoto K, Gupta D, Dziarski R. 2003. Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase. J. Biol. Chem. 278: 49044-49052, PMID: 14506276.
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, Dziarski R. 2005. Identification of serum N-acetylmuramoyl-L-alanine amidase as liver peptidoglycan recognition protein 2. Biochim. Biophys. Acta – Proteins and Proteomics 1752:34-46, PMID: 16054449.
Wang H, Gupta D, Li X, Dziarski R. 2005. Peptidoglycan recognition protein 2 (N-acetylmuramoyl-L-ala amidase) is induced in keratinocytes by bacteria through p38 kinase pathway. Infect. Immun. 73:7216-7225, PMID: 16239516.
Lu X, Wang M, Qi J, Wang H, Li X, Gupta D, Dziarski R. 2006. Peptidoglycan recognition proteins are a new class of human bactericidal proteins. J. Biol. Chem. 281: 5895-5907, PMID: 16354652.
Dziarski R, Gupta D. 2006. The peptidoglycan recognition proteins (PGRPs). Genome Biol. 7:232, p. 1-13, PMID: 16930467.
Wang M, Liu LH, Wang S, Li X, Lu X, Gupta D, Dziarski R. 2007. Human peptidoglycan recognition proteins require zinc to kill both Gram-positive and Gram-negative bacteria and are synergistic with antibacterial peptides. J. Immunol. 178: 3116-3125, PMID: 17312159.
Li X, Wang S, Qi J, Echtenkamp SF, Chatterjee R, Wang M, Boons G-B, Dziarski R, Gupta D. 2007. Zebrafish peptidoglycan recognition proteins are bactericidal amidases essential for defense against bacterial infections. Immunity 27: 518-529 (featured in an Immunity editorial), PMID: 17892854.
Royet J, Dziarski R. 2007. Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defenses. Nature Rev Microbiol. 5:264-277. PMID: 17363965.
Saha S, Qi J, Wang S, Wang, M, Li X, Kim Y-G, Núñez G, Gupta D, Dziarski R. 2009. PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation. Cell Host & Microbe 5: 137-150 (featured in a CHM editorial), PMID: 19218085.
Saha S, Jing X, Park SY, Wang S, Li X, Gupta D, Dziarski R. 2010. Peptidoglycan Recognition Proteins protect mice from experimental colitis by promoting normal gut flora and preventing induction of interferon-?. Cell Host & Microbe 8: 147-162 (featured on the cover and in a CHM editorial), PMID: 20709292.
Kashyap DR, Wang M, Liu L-H, Boons, G-J, Gupta D, Dziarski R. 2011. Peptidoglycan recognition proteins kill bacteria by activating protein-sensing two-component systems. Nature Med. 17: 676-683 (featured in a Nature Med. editorial), PMID: 21602801.
Park SY, Gupta D, Kim CH, 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, PMID: 21949809.
Park SY, Gupta D, Hurwich R, Kim CH, Dziarski R. 2011. Peptidoglycan recognition protein Pglyrp2 protects mice from psoriasis-like skin inflammation by promoting regulatory T cells and limiting Th17 responses. J. Immunol. 187: 5813-5823, PMID: 22048773.
Royet J, Gupta D, Dziarski R. 2011. Peptidoglycan recognition proteins: modulators of the microbiome and inflammation. Nature Rev Immunol. 11:837-851, PMID: 22076558.
Park SY, Jing X, Gupta D, Dziarski R. 2013. Peptidoglycan recognition protein 1 enhances experimental asthma by promoting Th2 and Th17 and limiting regulatory T cell and plasmacytoid dendritic cell responses. J. Immunol. 190: 3480-3492, PMID: 23420883.
Zulfiqar F, Hozo I, Rangarajan S, Mariuzza R, Dziarski R, Gupta D. 2013. Genetic association of peptidoglycan recognition protein variants with inflammatory bowel disease. PLoS One, 8(6):e67393. p. 1-14, PMID: 23840689.
Dziarski R. 2013. Innate immunity. In: Schaechter’s Mechanisms of Microbial Disease, 5th Edition, Engelberg NC, DiRita V, Dermody TS (eds), Chapter 6, Wolters Kluwer/Lippincott, Williams & Wilkins, pp 66-90.
Kashyap DR, Rompca A, Gaballa A, Helmann JD, Chan J, Chang CJ, Hozo I, Gupta D, Dziarski R. 2014. Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress. PLoS Pathog. 10:e1004280. p. 1-17, PMID: 25032698.
Jing X, Zulfiqar F, Park SY, Núñez G, Dziarski R, Gupta D. 2014. Peptidoglycan recognition protein 3 and Nod2 synergistically protect mice from dextran sodium sulfate-induced colitis. J Immunol. 193: 3055-3069, PMID: 25114103.
Dziarski R, Park SY, Kashyap DR, Dowd SE, Gupta D. 2016. Pglyrp-regulated gut microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii enhance and Alistipes finegoldii attenuates colitis in mice. PLoS One, 11(1): e0146162. p. 1-24, PMID: 26727498.
Dziarski R, Royet J, Gupta D. 2016. Peptidoglycan Recognition Proteins (PGRPs) and Lysozyme. In: Encyclopedia of Immunobiology, Ratcliffe MJH (ed), Academic Press/Elsevier Ltd, vol. 2, pp. 389-403.
See PubMed for complete list of publications: http://www.ncbi.nlm.nih.gov/pubmed/?term=dziarski