Department of Cell Genetics - Institute for Genetics - University of Cologne

Department of Cell Genetics
Institute for Genetics - University of Cologne
Department Head: Prof. Dr. Jonathan C. Howard


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Jonathan C. Howard: Curriculum Vitae - Publications - Research Grants

Recent Publications

The impact of Toxoplasma gondii on the mammalian genome.
Müller UB, Howard JC.
Curr Opin Microbiol. 2016 Apr 26;32:19-25. doi: 10.1016/j.mib.2016.04.009. PubMed, Article

Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection.
Maric-Biresev J, Hunn JP, Kurt O, Helms, JB, Martens S, Howard JC.
BMC Biol. 2016 Apr 20;14:33. doi: 10.1186/s12915-016-0255-4. PubMed, Article

The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.
Schulte K, Pawlowski N, Faelber K, Fröhlich C, Howard JC, Daumke O.
BMC Biol. 2016 Mar 2;14:14. doi: 10.1186/s12915-016-0236-7. PubMed, Article

The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase and regulated by the dense granule protein GRA7.
Hermanns T, Müller UB, Könen-Waisman S, Howard JC, Steinfeldt T
Cell Microbiol. 2016 18(2), 244259 doi:10.1111/cmi.12499 PubMed, Article


Identification of the Microsporidian Encephalitozoon cuniculi as a New Target of the IFN-γ-Inducible IRG Resistance Systems.
Ferreira-da-Silva MDF, Springer-Frauenhoff HM, Bohne W, Howard JC.
PLoS Pathog. 2014 Oct 30;10(10):e1004449. doi: 10.1371/journal.ppat.1004449 PubMed, Article

Innate resistance against Toxoplasma gondii: an evolutionary tale of mice, cats, and men.
Gazzinelli RT, Mendonça-Neto R, Lilue JC, Howard J, Sher A.
Cell Host Microbe. 2014 Feb 12;15(2):132-8. doi: 10.1016/j.chom.2014.01.004. PubMed, Article


Reciprocal virulence and resistance polymorphism in the relationship between Toxoplasma gondii and the house mouse.
Lilue J, Müller UB, Steinfeldt T, Howard JC.
eLife. 2013 Oct 29;2:e01298. doi: 10.7554/eLife.01298. PubMed, Article Access the recommendation on F1000Prime

Irgm1 (LRG-47), a regulator of cell-autonomous immunity, does not localize to mycobacterial or listerial phagosomes in IFN-γ-induced mouse cells.
Springer HM, Schramm M, Taylor GA, Howard JC.
J Immunol. 2013 Aug 15;191(4):1765-74. PubMed, Article


The arginine-rich N-terminal domain of ROP18 is necessary for vacuole targeting and virulence of Toxoplasma gondii.
Fentress SJ, Steinfeldt T, Howard JC, Sibley LD.
Cell Microbiol. 2012 Dec;14(12):1921-33. PubMed, Article

A Toxoplasma gondii pseudokinase inhibits host IRG resistance proteins.
Fleckenstein MC, Reese ML, Könen-Waisman S, Boothroyd JC, Howard JC, Steinfeldt T.
PLoS Biol. 2012;10(7): e1001358. PubMed, Article


The IRG protein-based resistance mechanism in mice and its relation to virulence in Toxoplasma gondii.
Howard JC, Hunn JP, Steinfeldt T.
Curr Opin Microbiol. 2011 Aug;14(4):414-21. PubMed, Article

Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy.
Traver MK, Henry SC, Cantillana V, Oliver T, Hunn JP, Howard JC, Beer S, Pfeffer K, Coers J, Taylor GA.
J Biol Chem. 2011 Sep 2;286(35):30471-80. PubMed, Article

The IFN-γ-inducible GTPase, Irga6, protects mice against Toxoplasma gondii but not against Plasmodium berghei and some other intracellular pathogens.
Liesenfeld O, Parvanova I, Zerrahn J, Han SJ, Heinrich F, Muñoz M, Kaiser F, Aebischer T, Buch T, Waisman A, Reichmann G, Utermöhlen O,
von Stebut E, von Loewenich FD, Bogdan C, Specht S, Saeftel M, Hoerauf A, Mota MM, Könen-Waisman S, Kaufmann SH, Howard JC.

PLoS One. 2011;6(6):e20568. PubMed, Article

The activation mechanism of Irga6, an interferon-inducible GTPase contributing to mouse resistance against Toxoplasma gondii
Pawlowski N, Khaminets A, Hunn JP, Papic N, Schmidt A, Uthaiah RC, Lange R, Vopper G, Martens S, Wolf E, Howard JC
BMC Biol. 2011 Jan 28;9(1):7. PubMed, Article

The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens.
Hunn JP, Feng CG, Sher A, Howard JC
Mamm Genome. 2011 Feb;22(1-2):43-54. PubMed, Article, Cover


Phosphorylation of Mouse Immunity-Related GTPase (IRG) Resistance Proteins Is an Evasion Strategy for Virulent Toxoplasma gondii.
Steinfeldt T, Könen-Waisman S, Tong L, Pawlowski N, Lamkemeyer T, SibleyLD, HunnJP, Howard JC
PLoS Biol. 2010;8(12): e1000576. PubMed, Article

Spontaneous focal activation of invariant natural killer T cells (iNKT cells) in mouse liver and kidney.
Zeng J, Howard JC
BMC Biol. 2010 Nov 30;8(1):142. PubMed, Article, Highlighted

Dynamin self-assembly and the vesicle scission mechanism: how dynamin oligomers cleave the membrane neck of clathrin-coated pits during endocytosis.
Pawlowski N
Bioessays. 2010;32(12):1033-1039. PubMed, Article, Cover

UNC93B1 mediates host resistance to infection with Toxoplasma gondii.
Melo MB, Kasperkovitz P, Cerny A, Könen-Waisman S, Kurt-Jones EA, Lien E, Beutler B, Howard JC, Golenbock DT, Gazzinelli RT
PLoS Pathog. 2010;6(8). pii: e1001071. PubMed, Article

The mouse resistance protein Irgm1 (LRG-47): a regulator or an effector of pathogen defense?
Hunn JP, Howard JC
PLoS Pathog. 2010;6(7):e1001008. PubMed, Article

Coordinated Loading of IRG Resistance GTPases on to the Toxoplasma gondii Parasitophorous Vacuole.
Khaminets A, Hunn JP, Könen-Waisman S, Zhao YO, Preukschat D, Coers J, Boyle JP, Ong YC, Boothroyd JC, Reichmann G, Howard JC
Cell Microbiol. 2010;12(7):939-61. PubMed, Article

Localisation and mislocalisation of the interferon-inducible immunity-related GTPase, Irgm1 (LRG-47) in mouse cells.
Zhao YO, Könen-Waisman S, Taylor GA, Martens S, Howard JC
PLoS One. 2010;5(1):e8648. PubMed, Article


Brucella abortus induces Irgm3 and Irga6 expression via type-I IFN by a MyD88-dependent pathway, without the requirement of TLR2, TLR4, TLR5 and TLR9.
Lapaque N, Muller A, Alexopoulou L, Howard JC, Gorvel JP
Microb Pathog. 2009;47(6):299-304. PubMed, Article

A Dedicated Promoter Drives Constitutive Expression of the Cell-Autonomous Immune Resistance GTPase, Irga6 (IIGP1) in Mouse Liver.
Zeng J, Parvanova IA, Howard JC
PLoS One. 2009;4(8):e6787. PubMed, Article

Modeling infectious disease in mice: co-adaptation and the role of host-specific IFNgamma responses.
Coers J, Starnbach MN, Howard JC
PLoS Pathog. 2009;5(5):e1000333. PubMed, Article

Toxoplasma gondii and the Immunity-Related GTPase (IRG) resistance system in mice: a review.
Zhao YO, Rohde C, Lilue JT, Könen-Waisman S, Khaminets A, Hunn JP, Howard JC
Mem Inst Oswaldo Cruz. 2009;104(2):234-40. PubMed, Article

Why didn't Darwin discover Mendel's laws?
Howard JC
J Biol. 2009;8(2):15. PubMed, Article, Special Darwin issue

Death and resurrection of the human IRGM gene.
Bekpen C, Marques-Bonet T, Alkan C, Antonacci F, Leogrande MB, Ventura M, Kidd JM, Siswara P, Howard JC, Eichler EE
PLoS Genet. 2009;5(3):e1000403. PubMed, Article

Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite vacuole disruption within primed macrophages.
Zhao Y, Ferguson DJ, Wilson DC, Howard JC, Sibley LD, Yap GS
J Immunol. 2009;182(6):3775-81. PubMed, Article

Disruption of the Toxoplasma gondii parasitophorous vacuole by IFNgamma-inducible immunity-related GTPases (IRG proteins) triggers necrotic cell death.
Zhao YO, Khaminets A, Hunn JP, Howard JC
PLoS Pathog. 2009;5(2):e1000288. PubMed, Article

Balance of Irgm protein activities determines IFN-gamma-induced host defense.
Henry SC, Daniell XG, Burroughs AR, Indaram M, Howell DN, Coers J, Starnbach MN, Hunn JP, Howard JC, Feng CG, Sher A, Taylor GA
J Leukoc Biol. 2009;85(5):877-85. PubMed, Article


The IRG proteins: a function in search of a mechanism.
Howard J
Immunobiology. 2008;213(3-4):367-75. PubMed, Article

Inactive and active states of the interferon-inducible resistance GTPase, Irga6, in vivo.
Papic N, Hunn JP, Pawlowski N, Zerrahn J, Howard JC
J Biol Chem. 2008;283(46):32143-51. PubMed, Article

Regulatory interactions between IRG resistance GTPases in the cellular response to Toxoplasma gondii.
Hunn JP, Koenen-Waisman S, Papic N, Schroeder N, Pawlowski N, Lange R, Kaiser F, Zerrahn J, Martens S, Howard JC
EMBO J. 2008;27(19):2495-509. PubMed, Article Access the recommendation on F1000Prime

Chlamydia muridarum evades growth restriction by the IFN-gamma-inducible host resistance factor Irgb10.
Coers J, Bernstein-Hanley I, Grotsky D, Parvanova I, Howard JC, Taylor GA, Dietrich WF, Starnbach MN
J Immunol. 2008;180(9):6237-45. PubMed, Article


Introduction: cell-autonomous immunity.
Howard JC
Microbes Infect. 2007;9(14-15):1633-5. PubMed, Article

Cell-autonomous immunity to Toxoplasma gondii in mouse and man.
Könen-Waisman S, Howard JC
Microbes Infect. 2007;9(14-15):1652-61. PubMed, Article

Evolution of immunity and pathogens.
Howard JC, Jack RS
Eur J Immunol. 2007;37(7):1721-3. PubMed, Article


The interferon-inducible GTPases.
Martens S, Howard J
Annu Rev Cell Dev Biol. 2006;22:559-89. PubMed, Article

Biogenesis of functional antigenic peptide transporter TAP requires assembly of pre-existing TAP1 with newly synthesized TAP2.
Keusekotten K, Leonhardt RM, Ehses S, Knittler MR
J Biol Chem. 2006;281(26):17545-51. PubMed, Article

Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse classic and non-classic lipopolysaccharides.
Lapaque N, Takeuchi O, Corrales F, Akira S, Moriyon I, Howard JC, Gorvel JP
Cell Microbiol. 2006;8(3):401-13. PubMed, Article


Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases.
Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, Reichmann G, Howard JC
PLoS Pathog. 2005;1(3):e24. PubMed, Article

Critical role for the tapasin-docking site of TAP2 in the functional integrity of the MHC class I-peptide-loading complex.
Leonhardt RM, Keusekotten K, Bekpen C, Knittler MR
J Immunol. 2005;175(8):5104-14. PubMed, Article

The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage.
Bekpen C, Hunn JP, Rohde C, Parvanova I, Guethlein L, Dunn DM, Glowalla E, Leptin M, Howard JC
Genome Biol. 2005;6(11):R92. PubMed, Article

Functional role of C-terminal sequence elements in the transporter associated with antigen processing.
Ehses S, Leonhardt RM, Hansen G, Knittler MR
J Immunol. 2005;174(1):328-39. PubMed, Article


Crystal structure of IIGP1: a paradigm for interferon-inducible p47 resistance GTPases.
Ghosh A, Uthaiah R, Howard J, Herrmann C, Wolf E
Mol Cell. 2004;15(5):727-39. PubMed, Article

Mechanisms regulating the positioning of mouse p47 resistance GTPases LRG-47 and IIGP1 on cellular membranes: retargeting to plasma membrane induced by phagocytosis.
Martens S, Sabel K, Lange R, Uthaiah R, Wolf E, Howard JC
J Immunol. 2004;173(4):2594-606. PubMed, Article


The distinct nucleotide binding states of the transporter associated with antigen processing (TAP) are regulated by the nonhomologous C-terminal tails of TAP1 and TAP2.
Bouabe H, Knittler MR
Eur J Biochem. 2003;270(22):4531-46. PubMed, Article

IIGP1, an interferon-gamma-inducible 47-kDa GTPase of the mouse, showing cooperative enzymatic activity and GTP-dependent multimerization.
Uthaiah RC, Praefcke GJ, Howard JC, Herrmann C
J Biol Chem. 2003;278(31):29336-43. PubMed, Article

A giant GTPase, very large inducible GTPase-1, is inducible by IFNs.
Klamp T, Boehm U, Schenk D, Pfeffer K, Howard JC
J Immunol. 2003;171(3):1255-65. PubMed, Article


Controlled elimination of clathrin heavy-chain expression in DT40 lymphocytes.
Wettey FR, Hawkins SF, Stewart A, Luzio JP, Howard JC, Jackson AP
Science. 2002;297(5586):1521-5. PubMed, Article


Functional asymmetry of the ATP-binding-cassettes of the ABC transporter TAP is determined by intrinsic properties of the nucleotide binding domains.
Daumke O, Knittler MR
Eur J Biochem. 2001;268(17):4776-86. PubMed, Article

Distinct functional properties of the TAP subunits coordinate the nucleotide-dependent transport cycle.
Alberts P, Daumke O, Deverson EV, Howard JC, Knittler MR
Curr Biol. 2001;11(4):242-51. PubMed, Article


Is a mutator analogous to the Ig hypermutator of the sheep ileal Peyer's patch active on MHC class I genes in the germ line?
Guethlein LA, Howard JC
Immunogenetics. 2000;51(6):462-72. PubMed, Article


The gene conversion hypothesis of MHC evolution: a review.
Martinsohn JT, Sousa AB, Guethlein LA, Howard JC
Immunogenetics. 1999;50(3-4):168-200. PubMed, Article

Nucleotide binding by TAP mediates association with peptide and release of assembled MHC class I molecules.
Knittler MR, Alberts P, Deverson EV, Howard JC
Curr Biol. 1999;9(18):999-1008. PubMed, Article

Antigen recognition.
Cresswell P, Howard J
Curr Opin Immunol. 1999;11(1):61-3. PubMed, Article


MHC class I molecules compete in the endoplasmic reticulum for access to transporter associated with antigen processing.
Knittler MR, Gülow K, Seelig A, Howard JC
J Immunol. 1998;161(11):5967-77. PubMed, Article

Two families of GTPases dominate the complex cellular response to IFN-gamma.
Boehm U, Guethlein L, Klamp T, Ozbek K, Schaub A, Fütterer A, Pfeffer K, Howard JC
J Immunol. 1998;161(12):6715-23. PubMed, Article


Cellular responses to interferon-gamma.
Boehm U, Klamp T, Groot M, Howard JC
Annu Rev Immunol. 1997;15:749-95. PubMed, Article