Reinhard Hinterleitner, Ph.D.
Campus: The Assembly, 5051 Centre Ave
Pittsburgh, PA 15213
- University of Chicago, Postdoc
- Medical University Innsbruck – Austria, Ph.D. (2012)
- University of Applied Sciences Vienna – Austria, M.S. (2007)
- Assistant Professor, Department of Immunology
IDENTIFY TRIGGERS THAT LEAD TO ABERRANT TYPE 2 IMMUNE-MEDIATED FOOD ALLERGIES
We have shown that enteric reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease (Science, 2017). Loss of oral tolerance to gluten antigen is characterized by proinflammatory T-helper 1 immune responses. However, in contrast to celiac disease, classical food allergies such as peanut allergy for example are initiated via T-helper 2 immune responses going wrong. One aim of my lab is to study and identify triggers that lead to aberrant T-helper 2 immune-mediated food allergies using genetically engineered mouse models, various immunological tools and by collaborating with the food allergy program at the University of Pittsburgh allowing us to translate our findings to human health.
IMPACT OF SOMATIC MUTATIONS ON INTESTINAL BARRIER INTEGRITY
Age-acquired somatic TET2 mutations increase the risk for hematopoietic malignancies. We have shown that microbial signals drive pre-leukemic myeloproliferation in a Tet2-deficient host (Nature, 2018), suggesting new ways of preventing disease development. In this study we have identified that defects in the small intestinal gut barrier lead to systemic bacteria translocation resulting in pre-leukemic myeloproliferation. One aim of my lab is to define the underlying mechanism of this gut barrier defect and to identify potential intestinal abnormalities in humans with somatic TET2 mutations.
INTESTINAL GENE MACHINE
From the very proximal part of the intestine, which is the duodenum, to the very distal part of the colon, this entire organ has highly-specialized site-specific functions and is characterized by differences in the composition of intestinal microbes and host immune cells residing in the epithelium and lamina propria. With the use of next generation sequencing we have identified site-specific genes and want to define their function and relevance under homeostasis and presence of inflammatory triggers using CRISPR-engineered genetically modified mice, organoid co-cultures and various molecular techniques
The Hinterleitner lab is currently accepting graduate students for rotations in the laboratory, as well as applications for postdoctoral fellows.
Meisel M#, Hinterleitner R#, Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado G, Lira S, Baier G, Chang EB, Eren MA, Weber CR, Busque L, Godley LA, Verdú EF, Barreiro LB, Jabri B. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 2018 May;557(7706):580-584. #contributed equally
Bouziat R#, Hinterleitner R#, Brown JJ#, Stencel-Baerenwald JE, Ikizler M, Mayassi T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA, Costes LMM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S, McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker HC, Kupfer SS, Guandalini S, Semrad C, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A, Dermody TS, Jabri B. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science 2017 Apr 7;356(6333):44-50
#contributed equally. Perspective in Science, New England Journal of Medicine, J Cell Physiol. Highlighted in Science Immunology, Nature Reviews Gastroenterology and Hepatology, Science Daily and various other news and media outlets.
Hinterleitner R, Jabri B. A dendritic cell subset designed for oral tolerance. Nature Immunology 2016 Apr 19;17(5):474-476.
Konjar Š#, Frising UC#, Ferreira C, Hinterleitner R, Mayassi T, Zhang Q, Blankenhaus B, Haberman N, Loo Y, Guedes J, Baptista M, Innocentin S, Stange J, Strathdee D, Jabri B, Veldhoen M. Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes. Science Immunology 2018 June 22;3(24). #contributed equally
Pierre JF, Hinterleitner R, Bouziat R, Hubert NA, Leone V, Miyoshi J, Jabri B, Chang EB. Dietary antioxidant micronutrients alter mucosal inflammatory risk in a murine model of genetic and microbial susceptibility. The Journal of Nutritional Biochemistry 2017 Dec 10;54:95-104
Minter MR, Hinterleitner R#, Meisel M#, Zhang C#, Leone V, Zhang X, Oyler-Castrillo P, Musch MW, Jabri B, Chang EB, Tanzi RE, Sisodia SS. Antibiotic-induced perturbations in microbial diversity during development alters amyloid pathology in APPSWE/PS1ΔE9 murine model of Alzheimer’s disease. Scientific Reports 2017 Sep 5;7(1):10411 #contributed equally
Meisel M, Mayassi T, Fehlner-Peach H, Koval JC, O'Brien SL, Hinterleitner R, Lesko K, Kim S, Bouziat R, Chen L, Weber CR, Mazmanian SK, Jabri B, Antonopoulos DA. Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis. ISME J 2017 Jan;11(1):15-30
Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson AM, Langdon WY, Ikeda F, Fededa JP, Cronin SJ, Nitsch R, Schultz-Fademrecht C, Eickhoff J, Menninger S, Unger A, Torka R, Gruber T, Hinterleitner R, Baier G, Wolf D, Ullrich A, Klebl BM, Penninger JM. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature 2014 Mar 27;507(7493):508-12.
Gruber T#, Hinterleitner R#, Hermann-Kleiter N, Meisel M, Pfeifhofer-Obermair C, Kleiter I, Wang M, Viola A, Baier G. Cbl-b mediates TGFb sensitivity by downregulation of the inhibitory SMAD7 in primary T cells. Journal of Molecular Cell Biology 2013 Dec;5(6):358-68. #contributed equally
Hinterleitner R#, Gruber T#, Pfeifhofer-Obermair C#, Lutz-Nicoladoni C#, Tzankov A, Schuster M, Penninger JM, Loibner H, Lametschwandtner G, Wolf D, Baier G. Adoptive transfer of siRNA cblb-silenced CD8+ T lymphocytes augments tumor vaccine efficacy in a B16 melanoma model. PLoS ONE 2012;7(9):e44295. #contributed equally