Associate Professor of Immunology
Phone: (919) 684-7109
Fax: (919) 684-2790
Vertebrates maintain a sophisticated network of specialized immune cells that includes innate lymphoid cells, professional antigen presenting cells, B cells and T cells. This network of professional immune cells is often equated with the immune system. However, more often than not professional immune cells exert their function indirectly through the secretion of pro-inflammatory cytokines that bind to their cognate receptors on the surface of non-immune cells and thereby instruct these non-immune cells to enter a state of heightened resistance towards intracellular pathogens. This cytokine-induced state of heightened resistance is due to the upregulation of various cell-autonomous defense modules. Our lab studies cytokine-induced cell-autonomous immunity and its role in infectious and autoimmune diseases. Specifically, we are in pursuit of finding answers to the following questions:
How does the innate immune system detect the location of bacterial and protozoan pathogens within an infected cell?
We are interested in Interferon (IFN)-stimulated host defense mechanisms against intracellular bacterial and protozoan pathogens that include Toxoplasma gondii, Chlamydia trachomatis, Legionella pneumophila and Shigella flexneri. To exert their antimicrobial activities, many IFN-induced host proteins must specifically localize to pathogen-containing vacuoles (PVs) or cytosolic pathogens. The mechanisms by which the host recognizes and discriminates between ‘non-self’ PVs or ‘non-self’ cytosolic bacteria and endogenous ‘self’ membranous structures, such as mitochondria or the Golgi apparatus, are not well understood. One of the main interests of our lab is to unveil molecular mechanisms that underlie the specific delivery of antimicrobial proteins to intracellular pathogens. Towards this goal we are taking the following complementary approaches:
- We conduct functional genomics screens to identify host genes required for the delivery of antimicrobial host proteins to intracellular sites of infection.
- We use bacterial genetics, cell biological and biochemical techniques to determine what PV- or bacteria-associated patterns are recognized by the innate immune response.
How do infected cells combat bacterial and protozoan pathogens?
We are interested in defining the network of cell-autonomous defense modules recruited to intracellular sites of infection and used by infected host cells to eliminate intracellular bacterial and protozoan pathogens. Towards this goal we are taking the following approaches:
We use proteomics to identify novel antimicrobial host proteins delivered to PVs and cytosolic bacterial pathogens
- We conduct functional genomics screens to identify host genes required for cell-autonomous host resistance
- We employ bacterial genetics to identify bacterial virulence factors required for the evasion of cell-autonomous defense pathways
What are the in vivo functions of cell-autonomous defense modules in host resistance, inflammation and autoimmunity?
To understand the in vivo relevance of cell-autonomous immune functions, we engineer and study genetic mouse models that include, for example, mice bearing Cas9/sgRNA-induced loss-of–function alleles in novel host defense genes. We use these mice to study the pathogenesis of infections diseases, sepsis and autoimmune diseases. A specific interest of the lab is to understand how the obligate intracellular bacterial pathogen C. trachomatis can cause chronic genital infections, infertility and other complications in women. We and others have found that humans and mice differ substantially in their respective IFN-induced cell-autonomous defense pathways and that these differences emerge as key determinants of host tropism. Therefore, we have developed mouse models that more accurately reflect the pathogenesis of human C. trachomatis infections. The study of these mouse models will support the development of more effective, alternative therapeutic strategies to treat Chlamydia and other microbial infections.
Jörn Coers received his M.Sc. degree in Biology from the University of Konstanz, Germany in 1999. While enrolled at the University of Konstanz, Dr. Coers conducted his M.Sc. thesis work in Craig Roy’s laboratory at the State University of New York, Stony Brook and later at Yale University where he continued to work as a research assistant until the spring of 2000. Dr. Coers made several important findings during his two and a half year stint in the Roy lab including the discovery of a chaperone complex in the bacterial pathogen Legionella pneumophila that is essential for the injection of virulence factors into host cells.
For his doctoral training, Dr. Coers employed transgenic mouse models to study the role of cytokine signaling in hematopoiesis at the German Cancer Research Center and at the University of Basel, Switzerland, in the laboratory of Radek Skoda. His work led to the discovery that aberrant expression of the thrombopoietin receptor protein can cause thrombocytosis due to a shift in the balance between thrombopoietin-induced proliferation of platelet precursor cells and removal of thrombopoietin by receptor mediated internalization in platelets.
For his postdoctoral training, he returned to the topic of host-pathogen interactions and applied his knowledge of mouse genetics to study infectious disease in the labs of Bill Dietrich and Michael Starnbach at Harvard Medical School. He identified members of a large family of Interferon-inducible GTPases as critical components in the innate immune response to the bacterial pathogen Chlamydia trachomatis, the cause of a common sexually transmitted disease resulting in sterility and the leading cause of preventable blindness globally.
In 2010, Dr. Coers began his independent laboratory as an Assistant Professor in the Department of Molecular Genetics and Microbiology at Duke University Medical Center. His laboratory is interested in the fundamental aspects of immune recognition of intracellular bacterial pathogens and the corresponding microbial counter-immune strategies. His lab uses applied genetic approaches in mice and mammalian cell lines to identify novel host genes required for innate immune responses and bacterial genetics to identify key bacterial genes involved in triggering or evading host immunity.
Danielle Pilla-Moffett, Shattuck Labs
Eric Feeley, Gyros Protein Technologies
Anthony Piro, Max-Planck Institute for Plant Breeding Research in Cologne, Germany
Ryan Finethy; University of Massachusetts Medical School
Jacob Dockterman, Duke Medical School
Mark Vignola, Intercept Pharmaceuticals
Arun Haldar, CSIR-Central Drug Research Institute
Kutsch, M., Sistemich, L., Lesser, CF., Goldberg, MB., Herrmann, C., Coers, J. Direct binding of polymeric GBP1 to LPS disrupts bacterial cell envelope functions. EMBO J 2020 10.15252/embj.2019104926
Kohler, KM.*, Kutsch, M.*, Piro, AS.*, Wallace, G., Coers, J.$, Baber, MF.$ Evolution of a C-terminal polybasic motif modulates pathogen recognition by primate guanylate binding proteins. mBio 2020 May 19;11(3):e00340-20 PMID: 32430466 (*Authors contributed equally to this study; $Authors contributed equally to this study)
Giebel, AM., Hu, S., Rajaram, K., Finethy, R., Toh, E., Brothwell, JA., Morrison, SG., Suchland, RJ., Stein, BD., Coers, J., Morrison, RP., Nelson, DE. Genetic screen in Chlamydia muridarum reveals role for an Interferon-induced host cell death program in antimicrobial inclusions rupture. mBio 2019 Apr 9;10(2) pii: e00385-19. PMID:30967464ope
Coers, J., Brown, HM., Hwang, S., Taylor, GA. Partners in anti-crime: how IFN-inducible GTPases and autophagy proteins team up in cell-intrinsic host defense. Current Opinion in Immunology 2018. 54:93-101. PMID: 29986303
Liu, BC., Sarhan, J., Panda, A., Muendlein, HI. Coers, J., Yamamoto, M., Isberg, RR., Poltorak, P. Constitutive-IFN maintains GBP expression required for release of bacterial components upstream of pyroptosis and anti-DNA responses. Cell Rep. 2018 Jul 3;24(1):155-168.e5. PMID: 29972777
Piro, AS., Hernandez, D., Luoma, S., Feeley, EM., Finethy, R., Yirga, A., Frickel, EM., Lesser, CF., Coers, J. Detection of cytosolic Shigella flexnerivia a C-terminal triple-ariginine motif of GBP1 inhibits actin-based motility. mBio 2017 Dec 12;8(6) pii: e01979-17. PMID: 29233899
Finethy, R., Luoma, S., Orench-Rivera, N., Feeley, EM., Haldar, AK., Yamaoto, Y., Kanneganti, TD., Kuehn, MJ., Coers, J. Inflammasome activation by bacterial outer membrane vesicles requires guanylate binding proteins. mBio 2017 Oct 3;8(5). pii: e01188-17. PMID: 28974614
Feeley, EM.*, Pilla-Moffett, D.*, Zwack, EE., Piro, AS., Finethy, R., Kolb, JP, Martinez, J., Brodsky, IE., Coers, J. Galectin-3 directs antimicrobial Guanylate Binding Proteins to vacuoles furnished with bacterial secretion systems. (*Authors contributed equally to this study). Proc Natl Acad Sci U.S.A. 2017 Feb 28;114(9):E1698-E1706 PMID: 28193861
Coers, J. Sweet host revenge: galectins and GBPs join forces at broken membranes. Cell Microbiol. 2017 Dec;19(12). doi: 10.1111/cmi.12793. PMID: 28973783
Sixt, BS., Bastidas, RJ., Finethy, R., Baxter, RM., Carpenter, VK., Kroemer, G., Coers, J., Valdivia, RH. The Chlamydia trachomatis inclusion membrane protein CpoS counteracts cellular surveillance and suicide programs. Cell Host and Microbe 2017 Jan 11;21(1):113-121. PMID: 28041929.
Zwack, EE., Feeley, EM., Bliska, JB., Yamamoto, M., Coers, J., Brodsky, IE. Guanylate Binding Proteins regulate inflammasome activation in response to Yersinia Type III translocon proteins. Infection and Immunity 2017 Sep 20;85(10). pii: e00778-16. PMID: 28784930
Haldar, AK., Piro, AS., Finethy, R., Espenschied, ST., Brown, HE., Giebel, AM., Frickel, E-A., Nelson, DE., Coers, J. Chlamydia trachomatis is resistant to inclusion ubiquitination and associated host defense in IFNg-primed human cells. mBio 2016. Dec 13;7(6). pii: e01417-16. PMID: 27965446
Pilla-Moffett, D., Barber, MF., Taylor, GA., Coers, J. IFN-inducible GTPases in host defense, inflammation and disease. Journal of Molecular Biology 2016 May 12. pii: S0022-2836(16)30142-5. PMID: 27181197
Coers, J., Finethy, R. Sensing the enemy, containing the threat: cell-autonomous immunity to Chlamydia trachomatis FEMS Microbiology Review 2016 Jul 29. pii: fuw027. PMID: 27476078
Finethy, R., Jorgensen, I., Haldar, AK., de Zoete, MR., Flavell, RA., Yamamoto, M., Nagarajan, UM., Miao, EA., Coers, J. Guanylate Binding Proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages. Infection and Immunity 2015 Dec; 83(12):4740-9. PMID: 26416908; PMC4645370.
Selected by I&I editors as article of significant interest. See Research Spotlight: Infection and Immunity 83(12): 4465
Haldar, AK., Finethy, R., Piro, AS., Feeley, EM., Pilla-Moffett, D., Foltz, C., Komatsu, M., Frickel, EM., Coers, J. Ubiquitin systems mark pathogen-containing vacuoles for host defense by Guanylate Binding Proteins. Proc Natl Acad Sci U.S.A. 2015 Oct 13;112(41):E5628-37. PMID: 26417105; PMC4611635.
FACULTY OF 1OOO: recommended article
NSF DISCOVERY FILES RADIO SPOT: http://news.science360.gov/archives/20151209
Aachoui, Y., Kajiwara, Y., Leaf, IA., Mao, D., Ting, JP., Coers, J., Aderem, A., Buxbaum, JD., Miao, EA. Canonical inflammasomes prime murine caspase-11, but not human caspase-4 during cytosol-invasive bacterial infection. Cell Host and Microbe 2015 Sep 9;18(3):320-32. PMID: 26320999;
Pilla, D., Hagar, JA., Haldar, AK., Mason, AK., Ernst, RK., Yamamoto M., Miao, EA., Coers, J. Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS. Proc Natl Acad Sci U.S.A. 2014 Apr 22;111(16):6046-51. PMID: 24715728
Haldar, AK., Saka, HA., Piro, AS., Dunn, JD., Henry, SC., Taylor, GA., Frickel, EM., Valdivia,RH., Coers, JC. IRG and GBP host resistance factors target aberrant, “non-self” vacuoles characterized by the missing of “self” IRGM proteins. PLoS Pathogens 2013 Jun;9(6):e1003414. PMID: 23785284