Hematopoeitic Stem Cells and Microenvironment

Arbeitsgruppe Prof. Dr. med. Götze

Research Interests

We are focused on studying hematopoietic stem cells in clonal hematopoiesis of indeterminate potential (CHIP) as well as in myeloid disorders such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In particular, we are interested in the interaction between mutated stem calls and their microenvironment (niche) in the bone marrow to identify and target critical pathways directing clonal evolution and enabling survival of leukemic stem calls through interaction with the stem cell niche, including characterization of extracellular vesicles. Current projects are focused on gaining a better understanding of which niche factors contribute to evolution from clonal hematopoiesis to myeloid disease as well as to relapse after allogeneic stemm cell transplantation with the ultimate goal of identifying niche dependencies that can be exploited for disease intervention.

Our projects are funded by the German Research Foundation (DFG), the Jose Carreras Leukämiestiftung, the German Cancer Consortium (Deusches Konsortium für Translationale Krebsforschung, DKTK) and the EU Horizon 2020 program. We have close collaborations with researchers at the Department of Mathematics for computational modeling of stem cell hierarchies and with the Jose Carreras Research Institute in Barcelona for research projects on epigenetics, chromatin, metabolism and cell fate and the Georg Speyer Haus in Frankfurt (Hind Medyouf) for in vivo and organoid niche models of myeloid diesease development.

PhD candidates interested in translational cancer research, cancer biology, hematopoieis, leukemia and/or stem cells are encouraged to contact us. Prior experience with stem cell assays, flow cytometry, bioinformatics, genomics or computational biology is highly desirable.

Selected recent Publications

Hecker JS*, Hartmann J*, Rivière J, BuckMC, van der Garde M, Rothenberg-Thurley M, Fischer L, Winter S, Ksienzyk B, Ziemann F, Solovey M, Rauner M, Tsourdi E, Sockel K, Schneider M, Kubasch AS, Nolde M, Hausmann D, Paulus AC, Lützner J, Roth A, Bassermann F, Spiekermann K, Marr C, Hofbauer LC, Platzbecker U, Metzeler KH*, Götze KS* (2021). CHIP & HIPs: Clonal Hematopoiesis is Common in Hip Arthroplasty Patients and Associates with Autoimmune Disease, Blood. 2021 Jun 17:blood.2020010163. doi: 10.1182/blood.2020010163. Epub ahead of print. PMID: 34139005.


Tirado-Gonzalez I, Descot A, Soetopo D, Nevmerzhitskaya A, Schaffer A, Kur IM, Czlonka E, Wachtel C, Tsoukala I, Muller L, Schafer AL, Weitmann M, Dinse P, Alberto E, Buck MC, Landry JJM, Baying B, Slotta-Huspenina J, Roesler J, Harter PN, Kubasch AS, Meinel J, Elwakeel E, Strack E, Tran Quang C, Abdel-Wahab O, Schmitz M, Weigert A, Schmid T, Platzbecker U, Benes V, Ghysdael J, Bonig H, Götze KS, Rothlin CV, Ghosh S, Medyouf H. AXL inhibition in macrophages stimulates host-versus-leukemia immunity and eradicates naive and treatment resistant leukemia. Cancer Discov. 2021 Jun 8:candisc.1378.2020. doi: 10.1158/2159-8290.CD-20-1378. Epub ahead of print. PMID: 34103328.

Bast L, Buck MC, Hecker JS, Oostendorp RAJ, Götze KS*, Marr C* (2021). Computational modeling of stem and progenitor cell kinetics identifies plausible hematopoietic lineage hierarchies. IScience 24, 102120.

Weickert MT*, Hecker JS*, Buck MC, Schreck C, Rivière J, Schiemann M, Schallmoser K, Bassermann F, Strunk D, Oostendorp RAJ, Götze KS (2021). Bone marrow stromal cells from MDS and AML patients show increased adipogenic potential with reduced Delta-like-1 expression. Sci. Rep. 11, 5944.

Müller-Thomas C, Heider M, Piontek G, Schlensog M, Bassermann F, Kirchner T, Germing U, Götze KS, Rudelius M. Prognostic value of indoleamine 2,3 dioxygenase in patients with higher-risk myelodysplastic syndromes treated with azacytidine. Br J Haematol. 2020 Aug;190(3):361-370. doi: 10.1111/bjh.16652. Epub 2020 Apr 29. PMID: 32350858.

Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Götze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellström-Lindberg E, Zeidan AM, Adès L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodisplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892. PMID: 31914241.

Wenk C, Garz A-K, Grath S, Huberle C, Witham D, Weickert M, Malinverni R, Niggemeyer J, Kyncl M, Hecker J, Pagel C, Mulholland CB, Müller-Thomas C, Leonhardt H, Bassermann F, Oostendorp RAJ, Metzeler KH, Buschbeck M, Götze KS (2018). Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis. Blood Adv. 11;2(23):3447–61.


Wermke M, Eckoldt J, Götze KS, Klein SA, Bug G, de Wreede LC, Kramer M, Stölzel F, von Bonin M, Schetelig J, Laniado M, Plodeck V, Hofmann WK, Ehninger G, Bornhäuser M, Wolf D, Theurl I, Platzbecker U. Enhanced labile plasma iron and outcome in AML and MDS patients undergoing allogeneic hematopoietic cell transplantation – results from the prospective multicenter observational ALLIVE trial (2018). Lancet Haematology, May;5(5):e201-e210.


Platzbecker U, Middeke JM, Sockel K, Herbst R, Wolf D, Baldus CD, …Götze KS…Thiede C. (2018) Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol.19(12):1668–79.


Platzbecker U, Germing U, Götze KS, Kiewe P, Mayer K, Chromik J, et al. (2017) Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 18(10):1338–47.


Park S, Hamel JF, Toma A, Kelaidi C, Thépot S, Campelo MD, Santini V, Sekeres MA, Balleari E, Kaivers J, Sapena R, Götze K, Müller-Thomas C, Beyne-Rauzy O, Stamatoullas A, Kotsianidis I, Komrokji R, Steensma DP, Fensterl J, Roboz GJ, Bernal T, Ramos F, Calabuig M, Guerci-Bresler A, Bordessoule D, Cony-Makhoul P, Cheze S, Wattel E, Rose C, Vey N, Gioia D, Ferrero D, Gaidano G, Cametti G, Pane F, Sanna A, Germing U, Sanz GF, Dreyfus F, Fenaux P (2017). Outcome of Lower-Risk Patients With Myelodysplastic Syndromes Without 5q Deletion After Failure of Erythropoiesis-Stimulating Agents. J Clin Oncol. 10;35(14):1591-1597.


Klaeger S, Heinzlmeir S, Wilhelm M, Polzer H, Vick B, Koenig PA, Reinecke M, Ruprecht B, Petzoldt S, Meng C, Zecha J, Reiter K, Qiao H, Helm D, Koch H, Schoof M, Canevari G, Casale E, Depaolini SR, Feuchtinger A, Wu Z, Schmidt T, Rueckert L, Becker W, Huenges J, Garz AK, Gohlke BO, Zolg DP, Kayser G, Vooder T, Preissner R, Hahne H, Tõnisson N, Kramer K, Götze KS, Bassermann F, Schlegl J, Ehrlich HC, Aiche S, Walch A, Greif PA, Schneider S, Felder ER, Ruland J, Médard G, Jeremias I, Spiekermann K, Kuster B (2017). The target landscape of clinical kinase drugs. Science.1;358(6367).


Garz A-K, Wolf S, Grath S, Gaidzik V, Habringer S, Vick B,Rudelius M, Ziegenhain C, Herold S, Weickert MT, Smets M, Peschel C, Oostendorp RAJ, Bultmann S, Jeremias I, Thiede C, Döhner K, Keller U, Götze KS (2017). Azacitidine combined with the selective FLT3 kinase inhibitor crenolanib disrupts stromal protection and inhibits expansion of residual leukemia-initiating cells in FLT3-ITD AML with concurrent epigenetic mutations. Oncotarget. 12;8(65):108738–59.


Schreck C, Istvánffy R, Ziegenhain C, Sippenauer T, Ruf F, Henkel L, Gärtner F, Vieth B, Florian MC, Mende N, Taubenberger A, Prendergast Á, Wagner A, Pagel C, Grziwok S, Götze KS, Guck J, Dean DC, Massberg S, Essers M, Waskow C, Geiger H, Schiemann M, Peschel C, Enard W, Oostendorp RA (2017). Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells. J Exp Med. 214(1):165-181.


Eichner R, Heider M, Fernández-Sáiz V, van Bebber F, Garz A-K, Lemeer S, …Götze KS, Kuster B and Bassermann F (2016). Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity. Nat Med. 22(7):735–43.


Herhaus P, Habringer S, Philipp-Abbrederis K, Vag T, Gerngross C, Schottelius M, Slotta-Huspenina J, Steiger K, Altmann T, Weißer T, Steidle S, Schick M, Jacobs L, Slawska J, Müller-Thomas C, Verbeek M, Subklewe M, Peschel C, Wester HJ, Schwaiger M, Götze K, Keller U (2016). Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia. Haematologica. Aug;101(8):932-40.


Jilg S, Reidel V, Müller-Thomas C, König J, Schauwecker J, Höckendorf U, Huberle C, Gorka O, Schmidt B, Burgkart R, Ruland J, Kolb HJ, Peschel C, Oostendorp RA, Götze KS, Jost PJ (2016). Blockade of BCL-2 proteins efficiently induces apoptosis in progenitor cells of high-risk myelodysplastic syndromes patients. Leukemia. Jan;30(1):112-23.

Application

Written applications including CV are welcome and should be forwarded by e-mail(link sends e-mail) to Prof. Katharina Götze.

 

Third party funding

Deutsche Jose Carreras Leukämiestiftung
DFG (FOR 2033, SFB 1243)
DKTK Joint Funding (CHOICE)
European Union Horizon 2020 innovative Training Network: INTERCEPT-MDS

 

Ihr Ansprechpartner

   

Prof. Dr. med. Katharina Götze Principal Investigator

Laboratory: Trogerstr. 32

E-Mail(link sends e-mail)