Roman Dziarski (Polish pronunciation: IPA: /ˈrɔ.man//ˈd͡ʑar.ski/ born December 11, 1949) is a Polish-born American immunologist and

microbiologist A microbiologist (from Ancient Greek, Greek ) is a scientist who studies microscopic life forms and processes. This includes study of the growth, interactions and characteristics of Microorganism, microscopic organisms such as bacteria, algae, f ...

. He is best known for his research on innate immunity and bacterial peptidoglycan, for discovering the family of human

peptidoglycan recognition protein Peptidoglycan recognition proteins (PGRPs) are a group of highly conserved pattern recognition receptors with at least one peptidoglycan recognition domain capable of recognizing the peptidoglycan component of the cell wall of bacteria. They are pr ...

s, which comprises PGLYRP1, PGLYRP2, PGLYRP3, and

PGLYRP4 Peptidoglycan recognition protein 4 (PGLYRP4, formerly PGRP-Iβ) is an antibacterial and anti-inflammatory innate immunity protein that in humans is encoded by the ''PGLYRP4'' gene. Discovery PGLYRP4 (formerly PGRP-Iβ), a member of a family o ...

, and for defining the functions of these proteins. Dziarski is currently Professor Emeritus of Microbiology and Immunology at Indiana University School of Medicine.

Education

From 1963 to 1967, Dziarski received his secondary education at Reytan High School (Polish: ''VI Liceum Ogólnokształcące im. Tadeusza Reytana'') in Warsaw, Poland, under the tutelage of the revered pedagogue, . From 1967 to 1972, Dziarski attended the

University of Warsaw The University of Warsaw ( pl, Uniwersytet Warszawski, la, Universitas Varsoviensis) is a public university in Warsaw, Poland. Established in 1816, it is the largest institution of higher learning in the country offering 37 different fields of ...

with a major in

Biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...

and

Microbiology Microbiology () is the scientific study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, bacteriology, prot ...

, which he studied under . He received his Bachelor of Sciences (BS) degree in 1971, and Master of Science (MS) degree in 1972. His MS Thesis was titled, ''Phenotypic expression of spontaneous mutations to nalidixic acid resistance in Escherichia coli K-12'', with Roman Mycielski as his thesis advisor. From 1972 to 1973, Dziarski studied English at

West London College West London College, legally known as the Ealing, Hammersmith and West London College is a large further and higher education college in West London, England, formed in 2002 by the merger between Ealing Tertiary College and Hammersmith and West ...

in London, England. From 1973 to 1977, Dziarski was a Research Scientist in the Department of Bacteriology at the National Institute of Public Health (Polish: '' Narodowy Instytut Zdrowia Publicznego – Państwowy Zakład Higieny''), Warsaw, Poland, where he performed research for his Doctor of Philosophy (Ph.D.) degree, which culminated in 1977 with the defense of his Ph.D. thesis, titled, ''Immunobiological properties of Staphylococcus aureus cell wall polysaccharides'', with Janusz Jeljaszewicz as his thesis advisor. In September 1977, Dziarski emigrated to the USA.

Academic positions

In 1977, Dziarski joined the Department of Microbiology, Immunology and Pathology at

Temple University School of Podiatric Medicine The Temple University School of Podiatric Medicine is a podiatric medical school associated with Temple University in Philadelphia, Pennsylvania. The school is located at 8th and Race Streets in downtown Philadelphia. The school was founded in 19 ...

in Philadelphia, Pennsylvania, USA, as a research associate and assistant professor. In 1978, he was promoted to assistant professor and in 1981 to associate professor. In 1985, Dziarski moved to the Department of Microbiology and Immunology at Indiana University School of Medicine–Northwest, in Gary, Indiana, USA, as an associate professor and a full member of the

Indiana University Indiana University (IU) is a system of public universities in the U.S. state of Indiana. Campuses Indiana University has two core campuses, five regional campuses, and two regional centers under the administration of IUPUI. *Indiana Universit ...

Graduate School, in Bloomington, Indiana, USA. In 1991, Dziarski was promoted to a Full Professor of Microbiology and Immunology with tenure. He held this position until his retirement in 2021, when he became Professor Emeritus of Microbiology and Immunology.

Scientific contributions

Role of peptidoglycan in innate immunity

In his early research, Dziarski focused on the role of bacterial peptidoglycan in innate immunity. He showed that peptidoglycan is an immunomodulator and a polyclonal activator of B lymphocytes. He determined the role of DNA synthesis, intracellular calcium,

protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...

, and inhibitory G proteins in peptidoglycan-induced polyclonal B lymphocyte activation. He also established the role of peptidoglycan and other polyclonal B cell activators in the induction of autoantibody responses in various models of autoimmunity.

Peptidoglycan receptors and cell activation pathways

In his subsequent research, Dziarski set out to identify peptidoglycan receptors on immune cells that mediate the cell-activating and immunomodulating effects of peptidoglycan. His early attempts using biochemical methods were not successful, as they were prone to nonspecific interactions and technical artifacts. He also showed that similar problems and artifacts plagued the early attempts to identify the cell receptors for bacterial

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

and other cell activators. The molecular biology approach to identifying the cell-activating peptidoglycan receptors was more successful. Using this approach, Dziarski and his research group, in collaboration with Dipika Gupta and her group (also at Indiana University School of Medicine), identified

CD14 CD14 (cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP). C ...

as the cell-activating receptor for peptidoglycan and showed that CD14 physically binds peptidoglycan. Furthermore, Dziarski's and Gupta's groups identified the involvement of several signal transduction molecules and pathways in peptidoglycan-induced cell activation. Dziarski also established that

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

s are the main pro-inflammatory mediators in human

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

s activated by peptidoglycan and other bacterial cell activators. Using similar molecular biology approach the research groups of Carsten J. Kirschning (at Tularik Inc.) and Douglas Golenbock (at

Boston University School of Medicine The Boston University Chobanian & Avedisian School of Medicine, formerly the Boston University School of Medicine, is one of the graduate schools of Boston University. Founded in 1848, the medical school was the first institution in the world ...

) in collaboration with Dziarski, discovered that TLR2 is the cell-activating receptor for peptidoglycan and other components of

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

. In the follow-up studies, Dziarski's and Gupta's groups identified the signal transduction pathway activated by peptidoglycan through TLR2 and verified that TLR2 is indeed the peptidoglycan cell-activating receptor.

Discovery of peptidoglycan recognition proteins

Dziarski's best known contribution to innate immunity is his research on mammalian

s (PGRPs). In 2001, Dziarski's and Gupta's groups discovered and cloned three human PGRPs, which they named PGRP-L, PGRP-Iα, and PGRP-Iβ (for long and intermediate size transcripts). They established that the human genome codes for a family of 4 PGRPs: PGRP-S (short PGRP), PGRP-L, PGRP-Iα, and PGRP-Iβ. Subsequently, the Human Genome Organization Gene Nomenclature Committee changed the gene symbols of PGRP-S, PGRP-L, PGRP-Iα, and PGRP-Iβ to '' PGLYRP1'', '' PGLYRP2'', '' PGLYRP3'', and ''

'', respectively, and this nomenclature is currently also used for other mammalian PGRPs. Dziarski and his collaborators showed that mammalian PGRPs are selectively expressed in immune and

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

Functions of peptidoglycan recognition proteins

Dziarski and his collaborators established that all

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

ian PGRPs bind bacterial peptidoglycan. Then, they identified the functions of human PGRPs: PGLYRP2 is a peptidoglycan-lytic enzyme, ''N''-acetylmuramoyl-L-alanine amidase, and PGLYRP1, PGLYRP3, and PGLYRP4 are directly bactericidal for both Gram-positive and Gram-negative bacteria. In further research, Dziarski's group established the mechanism of bacterial killing by human PGRPs. They showed that human PGRPs kill bacteria by simultaneously inducing three synergistic stress responses: oxidative stress, thiol stress, and metal stress, by interfering with the function of the bacterial respiratory electron transport chain. Dziarski also showed that bacterial killing by these PGRPs does not involve cell membrane permeabilization, cell wall hydrolysis, or osmotic shock, but is synergistic with

antibacterial peptides Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for an ...

Cloning and functions of zebrafish peptidoglycan recognition proteins

Collaborative research of Dipika Gupta's and Dziarski's groups also identified and cloned three

zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...

PGRPs and showed that they are highly expressed in eggs, developing embryos, and adult tissues that contact the external environment. They further showed that these PGRPs have both peptidoglycan-lytic amidase and bactericidal activities and are essential for defense against bacterial infections and survival of the developing zebrafish embryos.

In vivo role of mammalian peptidoglycan recognition proteins

Dziarski's group also identified several

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

functions of mammalian PGRPs. Dziarski showed that despite their bactericidal activity, mammalian PGRPs have only a limited role in defense against

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

s. Intranasal application of PGLYRP3 or PGLYRP4 in mice protects from intranasal lung infection with ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...

'' and ''Escherichia'' ''coli'', and ''PGLYRP1''-deficient mice are more sensitive to systemic infections with non-pathogenic bacteria (''

Micrococcus luteus ''Micrococcus luteus'' is a Gram-positive, to Gram-variable, nonmotile, coccus, tetrad-arranging, pigmented, saprotrophic bacterium that belongs to the family Micrococcaceae. It is urease and catalase positive. An obligate aerobe, ''M. luteus' ...

'' and ''Bacillus'' ''subtilis''). Dziarski's group further showed that mouse PGRPs play a role in maintaining healthy

microbiome A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably well ...

, because ''PGLYRP1''-, ''PGLYRP2''-, ''PGLYRP3''-, and ''PGLYRP4''-deficient mice have significant changes in the composition of their intestinal microbiomes. ''PGLYRP1''-deficient mice also have changes in their lung microbiome. Dziarski's and Gupta's groups further showed that mouse PGRPs play a role in maintaining anti- and pro- inflammatory homeostasis in the intestine, skin, lungs, and joints. They demonstrated that all four PGLYRPs protect mice from dextran sodium sulfate (DSS)-induced colitis and the effect of ''PGLYRP2'' and ''PGLYRP3'' on the intestinal microbiome is responsible for this protection. They showed that PGLYRP3 and PGLYRP4 are anti-inflammatory and protect mice from experimentally induced

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in puritis, itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens o ...

, and PGLYRP2 is also anti-inflammatory and protects mice from experimentally induced

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

-like inflammation. They also showed that some PGRPs have opposite effects, i.e., PGLYRP2 also has a pro-inflammatory effect, as it promotes the development of experimental

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

, and PGLYRP1 is pro-inflammatory and promotes experimentally induced

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

and skin

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

in mice. The pro-inflammatory effect of PGLYRP1 on asthma depends on the PGLYRP1-regulated intestinal microbiome.

Disease associations of peptidoglycan recognition proteins

In collaborative research, Dipika Gupta's and Dziarski's groups showed that patients with two forms of

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...

(IBD),

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

and ulcerative colitis, have significantly more frequent missense variants in all four ''PGLYRP'' genes than healthy control individuals. These results suggest that PGRPs may protect humans from these inflammatory diseases, and that mutations in ''PGLYRP'' genes may be among the genetic factors predisposing to these diseases.

Publications and research support

Dziarski authored over 150 scientific publications, which have 13,310 citations,

h-index The ''h''-index is an author-level metric that measures both the productivity and citation impact of the publications, initially used for an individual scientist or scholar. The ''h''-index correlates with obvious success indicators such as winn ...

of 48, and i10-index of 87. From 1979 to 2020, Dziarski was a Principal Investigator on more than 20 research grants, including 10 awards from the

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

Teaching

Dziarski is a dedicated educator. From 1978 to 1984, he taught Immunology and Microbiology to

podiatric medicine Podiatry () or podiatric medicine () is a branch of medicine devoted to the study, diagnosis, medical and surgical treatment of disorders of the foot, ankle, and leg. A Doctor of Podiatric Medicine (DPM), or a podiatrist, is a healthcare p ...

students at Temple University School of Podiatric Medicine. From 1985 to 2020, he taught Immunology, Microbiology, and elements of Pathology and Pharmacology to medical students at Indiana University School of Medicine–Northwest. He was a Course Director of Microbiology and Immunology, and in 1990 introduced an innovative

Problem-Based Learning Problem-based learning (PBL) is a student-centered pedagogy in which students learn about a subject through the experience of solving an open-ended problem found in trigger material. The PBL process does not focus on problem solving with a define ...

curriculum. He authored a chapter on Innate Immunity, published in three editions of the popular medical textbook, ''Schaechter’s Mechanisms of Microbial Disease'', and a chapter on peptidoglycan in ''Molecular Medical Microbiology'' textbook. Dziarski received seven Teaching Awards at Indiana University.

Awards and honors

* Indiana University Trustees’ Teaching Awards (2001, 2012, and 2018) * Indiana University School of Medicine Class of 2016 Faculty Teaching Award (2016) * Indiana University Outstanding Educator (2012, 2013, and 2014) * Innovation Fellow Award from the Society of Innovators, sponsored by Ivy Tech State College in Indiana (2007) * Joseph A. Negri Trust Award and Dedication of the Laboratory (2006) * Indiana University School of Medicine Eminent Scholar (1998 – 1999) * Editorial Board of ''Infection and Immunity'', the official journal of the American Society for Microbiology (1982 – 2020) * Editorial Board of ''Current Immunology Reviews'' (2004 – 2020) * Member of the American Association of Immunologists and Federation of American Societies for Experimental Biology (1982 – 2020) * Member of the American Society for Microbiology (1978 – 2020) * Dean's Award to the Best Graduating Student at the Faculty of Biology, University of Warsaw, Poland (1971)

Family

Dziarski's mother (Janina Dziarska, née Domańska) and father (Kazimierz W. Dziarski) were both dentists in Warsaw, Poland. Dziarski was married to Agnes Dziarski (née Rewkiewicz), a dentist, from 1971 to 1994. In 1996, Dziarski married Dipika Gupta, a biochemist and molecular biologist at Indiana University School of Medicine. Dziarski has three children: Matthew Dziarski, Alisha Dziarski, and Anjali Dziarski.

References

{{DEFAULTSORT:Dziarski, Roman Polish microbiologists Scientists from Warsaw 1949 births Living people Indiana University School of Medicine faculty Temple University faculty Polish emigrants to the United States