Nachwuchsgruppe Dr. Erik T. Orberg
Microbiome-based therapies of intestinal damage in leukemia and stem cell transplantation
Microbial triggers of onset, progression and relapse in hematological malignancies
Our reseach focuses on the cellular and molecular interactions between the microbiome, the gastrointestinal (GI) mucosa and the mucosal immune system in humans. We are interested in how microbiota modulate innate and adaptive immune pathways and how they influence the intestinal and hematopoietic stem cell niches in cancer and stem cell transplantation.
Microbial diversity is a strong predictor of survival in various hematological malignancies. Foremost, our group seeks to understand the microbiome signatures that contribute to positive clinical outcomes, how these bacteria mediate protection of mucosal barriers and the molecular mechanisms by which they do so. Specifically, we are interested in microbial products that can exert protective effects on the GI epithelium with its associated stem cell and immune cell compartments.
Conversely, there is ample evidence that microbial signatures can drive cancer. In B-cell malignancies such as multiple myeloma and chronic lymphocytic leukemia, tumor growth results from B-cell-receptor signaling upon binding of unknown antigens. Confident that these antigens are microbiome-derived, our apporach aims to identify microbiome signatures in progressive, refractory and relapsed disease.
We are part of the collaborative research center 1371, a DFG-funded consortium uniquely focused on microbiome in the context of inflammation and cancer. Here, our distinction results from the combination of clinical expertise in hematological malignancies, stem cell transplantation and cellular therapies with rigorous collection of human bio-samples and matching clinical data and integration in cutting-edge analyitical pipelines at the consortium.
Our clinical aim is to develop microbiome-based therapeutic approaches that can protect the GI epithelium, provide resistance to intensive chemotherapy and irradiation, and induce regenaration in the context of allogeneic immune reactions after stem cell transplantation.
Our aim for translational research is to define microbial communities specific to progression and relapse of mature B-cell malignancies. By transferring these communities into pre-clinical models, we aim unravel mechanisms by which microbiome can drive cancer.
We cooperate closey with AG Heidegger (Med. III, Rechts der Isar) and AG Poeck (Med. III, University Hospital of Regensburg).
Vision Zero Award 2019 des Netzwerks gegen Darmkrebs
Fischer JC, Bscheider M, Göttert S, Thiele Orberg E, Combs SE, Bassermann F, Heidegger S, Haas T, Poeck H. Type I interferon signaling before hematopoietic stem cell transplantation lowers donor T cell activation via reduced allogenicity of recipient cells.
Sci Rep. 2019 Oct 18;9(1):14955.
Chung L, Thiele Orberg, Geis AL, Chan JL, Fu K, DeStefano Shields CE, Dejea CM, Fathi P, Chen J, Finard BB, Tam AJ, McAllister F, Fan H, Wu X, Ganguly S, Lebid A, Metz P, Van Meerbeke SW, Huso DL, Wick EC, Pardoll DM, Wan F, Wu S, Sears CL, Housseau F.
Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells.
Cell Host Microbe. 2018Feb 14;23(2):203-214.e5.
Thiele Orberg E, Fan H, Tam AJ, Dejea CM, Destefano Shields CE, Wu S, Chung L, Finard BB, Wu X, Fathi P, Ganguly S, Fu J, Pardoll DM, Sears CL, Housseau F.
The myeloid immune signature of enterotoxigentic Bacteroides fragilis-induced murine colon tumorigenesis.
Mucosal Immunol. 2017 Mar;10(2):421-433.
Tina Eismann, Medizindoktorandin
Sophia Göldel, Medizindoktorandin
Melanie Tiefgraber, wissenschaftliche Mitarbeiterin
Third party funding
Else Kröner-Fresenius-Stiftung: Forschungskolleg "Mikrobielle Trigger als Auslöser von Krankheiten"(link is external)
Deutsches Konsortium für Translationale Krebsforschung: School of Oncology (link is external)
Deutsche Gesellschaft für Innere Medizin: Clinician Scientist Programm