Medizinische Klinik 2
Prof. Christian Brandts, MD
University Hospital Frankfurt
Goethe University
Theodor-Stern-Kai 7
60590 Frankfurt
Phone: +49 (0) 69 / 6301 - 87334 (office)
Fax: +49 (0) 69 / 6301 - 83833
Email: brandts[at]em.uni-frankfurt.de
Christian Brandts, Principal Investigator
Shabnam Shaid, MD, Post-doctoral fellow, Laboratory coordinator
Ibrahim Polat, MD, Post-doctoral fellow
Sebastian Koschade, MD, Post-doctoral fellow
Fatima Baker, PhD student
Laura Meyer, PhD student
Marlyn Thölken, MTA
Lea Hermann, MD student
Susanna Hock, MD student
Our research group focusses on the role of two degradative pathways involved in cancer: autophagy and proteasomal degradation. We use a combination of biochemical, cellular and genetic models to investigate their role in acute leukemia and solid tumors.
Acute myeloid leukemia (AML) is a hierarchical disease of the bone marrow originating from a leukemia stem cell (LSC). A similar hierarchy is observed in solid tumors. Posttranslational modifications, such as phosphorylation and ubiquitination, are highly relevant during the process of malignant transformation. Functional ubiquitination is required at multiple steps of protein quality control. Autophagy is a fundamental degradation process to maintain cellular homeostasis by removing large protein complexes and damaged organelles, thereby serving as an essential cellular quality control system. Our laboratory is investigating how to target these degradation pathways to potentially develop novel therapies for cancer patients.
As part of the SFB1177 on Selective Autophagy, our research group has demonstrated that the process of selective autophagy plays an essential role in the development of leukemia. The targeted elimination of substrates with the help of autophagy receptors is critical for efficient leukemogenesis. The dynamic process of autophagic flux is highly active in AML blasts (including LSCs) compared to normal hematopoietic stem and progenitor cells.
How does autophagy prevent malignant transformation? How does autophagy support cancer cells to maintain their malignant phenotype? Can we use this knowledge to develop novel cancer therapies?
Our laboratory aims to answer these questions, in particular by identifying the underlying mechanism and investigating the therapeutic potential of targeting cancer cells by autophagy inhibition. Specifically, we are exploring the contribution of selective autophagy to cancer development and progression, as well as in treatment resistance. Our translational research laboratory makes use of genetic mouse models, proteomics, primary tumor material and clinical data, aiming at bringing results from the laboratory towards clinical trials.
We are always interested in applications from excellent students and postdocs that are truly excited about cancer research.
Shabnam Shaid, MD
Brandts Laboratory
University Hospital Frankfurt
Goethe University
Building 25A, 3rd Floor, Room 304
Theodor-Stern-Kai 7
60590 Frankfurt
Phone: +49 69 6301 86709 (office)
Phone: +49 69 6301 7279 (lab)
Email: shaid[at]med.uni-frankfurt.de
Or
Prof. Christian Brandts, MD
University Hospital Frankfurt
Goethe University
Theodor-Stern-Kai 7
60590 Frankfurt
Phone: +49 69 6301 87334 (office)
Fax: +49 69 / 6301 - 83833
Email: brandts[at]em.uni-frankfurt.de
Ortmann CA, Dorsheimer L, Abou-El-Ardat K, Hoffrichter J, Assmus B, Bonig H, Scholz A, Pfeifer H, Martin H, Schmid T, Brüne B, Scheich S, Steffen B, Riemann J, Hermann S, Dukat A, Bug G, Brandts CH, Wagner S, Serve H, Rieger MA. Cell Rep. 2019 May 14;27(7):2022-2028.
Gröschel S, Hübschmann D, Raimondi F, Horak P, Warsow G, Fröhlich M, Klink B, Gieldon L, Hutter B, Kleinheinz K, Bonekamp D, Marschal O, Chudasama P, Mika J, Groth M, Uhrig S, Krämer S, Heining C, Heilig CE, Richter D, Reisinger E, Pfütze K, Eils R, Wolf S, von Kalle C, Brandts C, Scholl C, Weichert W, Richter S, Bauer S, Penzel R, Schröck E, Stenzinger A, Schlenk RF, Brors B, Russell RB, Glimm H, Schlesner M, Fröhling S. Nat Commun. 2019 Apr 9;10(1):1635.
Chaikuad A, Koschade SE, Stolz A, Zivkovic K, Pohl C, Shaid S, Ren H, Lambert LJ, Cosford NDP, Brandts CH, Knapp S. Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2). Biochem J 2019 Mar;476(5):875–87.
Poluzzi C, Nastase M-V, Zeng-Brouwers J, Roedig H, Hsieh LT-H, Michaelis JB, Buhl EM, Rezende F, Manavski Y, Bleich A, Boor P, Brandes RP, Pfeilschifter J, Stelzer EHK, Münch C, Dikic I, Brandts C, Iozzo R V., Wygrecka M, Schaefer L. Biglycan evokes autophagy in macrophages via a novel CD44/Toll-like receptor 4 signaling axis in ischemia/reperfusion injury. Kidney Int. 2019 Mar;95(3):540–62.
Nguyen TD, Shaid S, Vakhrusheva O, Koschade SE, Klann K, Thölken M, Baker F, Zhang J, Oellerich T, Sürün D, Derlet A, Haberbosch I, Eimer S, Osiewacz HD, Behrends C, Münch C, Dikic I, Brandts CH. Loss of the selective autophagy receptor p62 impairs murine myeloid leukemia progression and mitophagy. Blood 2019 Jan;133(2):168–79.
Bohnenberger H, Kaderali L, Ströbel P, Yepes D, Plessmann U, Dharia N V, Yao S, Heydt C, Merkelbach-Bruse S, Emmert A, Hoffmann J, Bodemeyer J, Reuter-Jessen K, Lois A-M, Dröge LH, Baumeister P, Walz C, Biggemann L, Walter R, Häupl B, Comoglio F, Pan K-T, Scheich S, Lenz C, Küffer S, Bremmer F, Kitz J, Sitte M, Beißbarth T, Hinterthaner M, Sebastian M, Lotz J, Schildhaus H-U, Wolff H, Danner BC, Brandts C, Büttner R, Canis M, Stegmaier K, Serve H, Urlaub H, Oellerich T. Comparative proteomics reveals a diagnostic signature for pulmonary head-and-neck cancer metastasis. EMBO Mol Med. 2018 Sep;10(9):e8428.
Demirel Ö, Balló O, Reddy PNG, Vakhrusheva O, Zhang J, Eichler A, Fernandes R, Badura S, Serve H, Brandts C. SOCS1 function in BCR-ABL mediated myeloproliferative disease is dependent on the cytokine environment. PLoS One. 2017 Jul 28;12(7):e0180401.
Jennewein L, Ronellenfitsch MW, Antonietti P, Ilina EI, Jung J, Stadel D, Flohr L-M, Zinke J, von Renesse J, Drott U, Baumgarten P, Braczynski AK, Penski C, Burger MC, Theurillat J-P, Steinbach JP, Plate K-H, Dikic I, Fulda S, Brandts C, Kögel D, Behrends C, Harter PN, Mittelbronn M. Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas. Oncotarget. 2016 Apr;7(15):20016–32.
Zhang J, Vakhrusheva O, Bandi SR, Demirel Ö, Kazi JU, Fernandes RG, Jakobi K, Eichler A, Rönnstrand L, Rieger MA, Carpino N, Serve H, Brandts CH. The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness. Stem Cell Reports. 2015 Oct;5(4):633–46.
Felzen V, Hiebel C, Koziollek-Drechsler I, Reißig S, Wolfrum U, Kögel D, Brandts C, Behl C, Morawe T. Estrogen receptor α regulates non-canonical autophagy that provides stress resistance to neuroblastoma and breast cancer cells and involves BAG3 function. Cell Death Dis 2015 Jul;6(7):e1812–e1812.
Wichmann C, Quagliano-Lo Coco I, Yildiz Ö, Chen-Wichmann L, Weber H, Syzonenko T, Döring C, Brendel C, Ponnusamy K, Kinner A, Brandts C, Henschler R, Grez M. Activating c-KIT mutations confer oncogenic cooperativity and rescue RUNX1/ETO-induced DNA damage and apoptosis in human primary CD34+ hematopoietic progenitors. Leukemia 2015 Feb 4;29(2):279–89.
Oellerich T, Oellerich MF, Engelke M, Munch S, Mohr S, Nimz M, Hsiao H-H, Corso J, Zhang J, Bohnenberger H, Berg T, Rieger MA, Wienands J, Bug G, Brandts C, Urlaub H, Serve H. 2 integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis. Blood 2013 May;121(19):3889–99.
de Bruin AM, Demirel O, Hooibrink B, Brandts CH, Nolte MA. Interferon- impairs proliferation of hematopoietic stem cells in mice. Blood 2013 May;121(18):3578–85.
Shaid S, Brandts CH, Serve H, Dikic I. Ubiquitination and selective autophagy. Cell Death Differ. 2013;20(1):21–30.
Reddy PNG, Sargin B, Choudhary C, Stein S, Grez M, Muller-Tidow C, Berdel WE, Serve H, Brandts CH. SOCS1 cooperates with FLT3-ITD in the development of myeloproliferative disease by promoting the escape from external cytokine control. Blood 2012 Aug;120(8):1691–702.
Bandi S.*, Brandts C.*, Rensinghoff M., Grundler R., Tickenbrock L., Duyster J., Berdel W.E. Müller-Tidow C. Serve H. and Sargin B. (2009) E3 ligase-defective Cbl mutants lead to myeloproliferative disease. Blood 114, 4197-208. *equal contribution
Choudhary C., Olsen J.V., Brandts C., Cox J., Reddy PK, Böhmer F, Gerke V, Schmidt-Arras D.E., Berdel W.E., Müller-Tidow C., Mann M. and Serve H. (2009) Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36, 326-39.
Brandts C.H., Berdel W.E. and Serve H. (2007). Oncogenic signaling in acute myeloid leukemia. Curr Drug Targets 8, 237-46. (review)
Choudhary C., Brandts C., Schwable J., Tickenbrock L., Sargin B., Ueker A., Bohmer F.D., Berdel W.E., Muller-Tidow C. and Serve H. (2007). Activation mechanisms of STAT5 by oncogenic Flt3-ITD. Blood 110, 370-4.
Choudhary C., Schwable J., Brandts C., Tickenbrock L., Sargin B., Kindler T., Fischer T., Berdel W.E., Muller-Tidow C. and Serve H. (2005). AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood 106, 265-73.
Brandts C.H., Sargin B., Rode M., Biermann C., Lindtner B., Schwable J., Buerger H., Muller-Tidow C., Choudhary C., McMahon M., Berdel W.E. and Serve H. (2005). Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation. Cancer Res 65, 9643-50.