Kasper Hoebe, PhD
Appointment
Assistant Professor
Email
kasper.hoebe@cchmc.org
Phone
513-803-1056
Fax
513-636-5355
Credentials
BS: Biology; Ultrecht University, The Netherlands, 1994
PhD: Immunology/ Pharmacology; Ultrecht University, The Netherlands, 2001
Research
Our laboratory is focused on a better understanding of the innate-adaptive connection. Previous work in our laboratory suggests that NK cells discharge an important role in the onset of adaptive immune responses including CD8+ T CD4+ T and B cell responses. NK cells are able to recognize a variety of target cells, including tumor cells, stressed cells or infected cells, via receptor –mediated interactions involving "missing self", "induced self" or recognition of pathogen-derived molecules. Upon administration of antigen-expressing cells that exhibit "missing self", NK cells induce cell death and subsequently prompt a strong CD8+ T, CD4+ T and B cell response. Our laboratory applies a forward genetic approach using ENU mutagenesis to identify key components in NK cell function and subsequent CD8+ T cell responses via the above described cell death pathway. In addition, we aim to exploit this pathway in the design of effective vaccines that promote strong cell-mediated and humoral immunity.
Publications, Most Recent
Hoebe K, Beutler B. Forward genetic analysis of TLR-signaling pathways: An evaluation. Advanced Drug Delivery Reviews 2008 [in press].
Rutschmann S, Hoebe K. Dissecting innate immunity by germline mutagenesis.Immunology 2008;123(4):459-68.
Baccala R, Hoebe K, Kono DH, Beutler B, Theofilopoulos AN. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity.Nature Med 2007;13(5);543–51.
Brinkmann MM, Spooner E, Hoebe K, Beutler B, Ploegh HL, Kim YM. The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling.J Cell Biol 2007;177(2):265-75.
Crozat K, Hoebe K, Ugolini S, Hong NA, Janssen E, Rutschmann S, Mudd S, Sovath S, Vivier E, Beutler B. Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. J Exp Med 2007;204(4):853-63.
Gavin AL, Hoebe K, Duong B, Ota T, Martin C, Beutler B, Nemazee D. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling.Science 2006;314(5807):1936-8.
Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, Alcais A, Picard C, Mahfoufi N, Nicolas N, Lorenzo L, Plancoulaine S, Senechal B, Geissmann F, Tabeta K, Hoebe K, Du X, Miller RL, Heron B, Mignot C, de Villemeur TB, Lebon P, Dulac O, Rozenberg F, Beutler B, Tardieu M, Abel L, Casanova JL. Herpes simplex virus encephalitis in human UNC-93B deficiency.Science 2006;314(5797): 308-12.
Hoebe K, Jiang Z, Tabeta K, Du X, Georgel P, Crozat K, Beutler B. Genetic analysis of innate immunity.Adv Immunol 2006;91:175-226.
Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, Zajonc DM, Ben-Menachem G, Ainge GD, Painter GF, Khurana A, Hoebe K, Behar SM, Beutler B, Wilson IA, Tsuji M, Sellati TJ, Wong CH, Kronenberg M. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.Nat Immunol 2006;7(9): 978-86.
Janssen E, Tabeta K, Barnes MJ, Rutschmann S, McBride S, Bahjat KS, Schoenberger SP, Theofilopoulos AN, Beutler B, Hoebe K. Efficient T cell activation via a Toll-Interleukin 1 Receptor-independent pathway.Immunity 2006;24(6):787-99.
Hoebe K, Beutler B. TRAF3: a new component of the TLR-signaling apparatus.Trends Mol Med 2006;12(5):187-9.
Beutler B, Jiang Z, Georgel P, Crozat K, Croker B, Rutschmann S, Du X, Hoebe K. Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large.Ann Review of Immunol 2006;24:353-89.
Tabeta K, Hoebe K, Janssen E, Du X, Georgel P, Crozat K, Mudd S, Mann N, Sovath S, Goode J, Shamel L, Herskovits AA, Portnoy DA, Cooke M, Tarantino LM, Wiltshire T, Steinberg B, Grinstein S, Beutler B. The induced mutation 3d disrupts signaling via toll-like receptors 3, 7 and 9 and exogenous antigen presentation.Nature Immun 2006;7:156-64.
Hoebe K, Beutler B. Unraveling innate immunity using large scale N-ethyl-N-nitrosourea mutagenesis.Tissue Antigens 2005;65:395-401.
Mattner J, DeBord K, Ismail N, Goff R, Cantu III C, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N, Hoebe K, Schneewind O, Walker D, Beutler B, Teyton L, Savage P, Bendelac A. Both exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections.Nature 2005;434:525-9.
Hoebe K, Georgel P, Rutschmann S, Du X, Mudd S, Crozat K, Sovath S, Shamel L, Hartung T, Zahringer U, Beutler B. CD36 is a sensor of diacylglycerides.Nature 2005;433:523-7.
Hoebe K, Janssen E, Beutler B. The interface between innate and adaptive immunity.Nat Immunol 2004;5(10):971-4.
Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection.Proc Natl Acad Sci USA 2004;101:3516-21.
Weighardt H, Jusek G, Mages J, Lang R, Hoebe K, Beutler B, Holzmann B. Identification of a TLR4- and TRIF-dependent activation program of dendritic cells.Eur J Immunol 2004;34(2):558-64.
Hoebe K, Janssen EM, Kim SO, Alexopoulou L, Flavell RA, Han J, Beutler B. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways.Nat Immunol 2003;4:1223-9.
Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sovath S, Han J, Beutler B. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.Nature 2003;424:743-8.
Book Chapters
Hoebe K. Genetic dissection of TLR signaling using ENU mutagenesis. In: Methods of Molecular Biology. Editors, O' Neill L, Mc Coy C. Humana Press. 2007
Georgel P, Du X, Hoebe K, Beutler B. ENU mutagenesis in mice. In: Methods of Molecular Biology. Editors, Ewbank J, Vivier E. Humana Press. 2007
Hoebe K and Beutler B. TLRs as bacterial sensors. In: "Toll-like receptors in Inflammation". Editors O'Neill L, Brint E, 2006, Birkhauser Verlag Basel/Switzerland.
Presentations, Most Recent
Pattern-recognition receptors in human disease, Biochemical Society meeting, Cambridge, UK, August 2007.
EuroCancer Meeting, Paris, France, June 2007
EMBO conference on molecular and cellular mechanisms of immune regulation, Sardinia, Italy, May 2007
Keystone Symposium on HIV Vaccines: From Basic Research to Clinical Trials. March 25 - 30, 2007
International Workshop "Toll-like receptors and beyond", Kloster Seeon, Germany, 18-21 March, 2007
Melanoma Symposium, "Overcoming Barriers to Immune Therapy in Melanoma", November 11, 2006, La Jolla, California, USA
32nd Annual La Jolla Immunology Conference, October 10-12, La Jolla, CA
Trans-kingdom Innate Immunity Workshop Sept. 29 - Oct. 1, 2006 Asilomar Conference Center, California
American Society for Microbiology 106th General Meeting, May 21-26th, Orlando, Florida
38th Annual Meeting of the Society for Leukocyte Biology, September 21-24, 2005, Oxford, England
The Molecular Pathogenesis of Infectious and Inflammatory Eye Research Conference, September 16-18, 2005 Cleveland Ohio.
MUGEN_Transgenesis Workshop in Luminy Marseilles, September 8 – September 10.
From Innate Immunity to Vaccines, June 14-15, 2005, San Diego, CA
IMV 2005, The Second International Conference on Immunopotentiators in Modern Vaccines 18-20 May 2005, Malaga, Spain
Keystone Symposium, "Dendritic Cells at the Center of Innate and Adaptive Immunity," organized in Vancouver, BC on Feb. 1–7
Related Areas
This person works in these other areas at Cincinnati Children's Hospital Medical
Center:
