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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Duque Laboratory

Acute leukemias and allogeneic stem cell transplantation

Scientific focus

The work of our group is focused on the study of molecular pathomechanisms in acute leukemias and on translational studies in allogeneic hematopoietic cell transplantation.

Although the treatment of the acute leukemias has been improved during the last decades, there are still many patients not surviving the disease being relapse and chemotherapy-related complications the main causes of death. Most of survivors are young and therefore very susceptible to the negative long-term effects of chemo- and radiotherapy.  In contrast, older patients or patients with comorbidities did not qualify for current intensified therapy regimens being treated with a palliative intention.

We aim to identify novel molecular targets and mechanisms of resistance to small molecules and chemotherapy using novel engineered leukemia mouse models as well as unbiased approaches as shRNA library screen, chromatin immunoprecipitation sequencing and global transcriptome analysis.  We employ defined genetic models as the chimeric fusion proteins E2A-PBX1 in acute lymphoblastic leukemias and AML1-ETO in acute myeloid leukemia.  Our long-term goal is to develop novel and more rational therapeutic approaches to contribute to the improvement of survival and quality of life of patients

A second major research focus of my group is the identification of molecular markers and clinical parameters including microbiome composition to assess risk for GvHD and relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and for non-relapse mortality after autologous hematopoietic cell transplantation (auto-HCT). Although allo-HCT and auto-HCT are effective curative treatment options for several neoplastic and non-neoplastic diseases, these procedures are not devoid of complications.

Relapse of the underlying disease and Graft-versus-Host Disease (GvHD) are frequent complications after allo-HCT, they contribute to morbidity and mortality and are the main cause of treatment failure. We aim to establish a non-invasive monitoring of circulating nucleic acids and to identify clinical parameters for early detection of relapse and/or GvHD in patients undergoing allo-HCT.

In addition, we are also investigating clinical factors, which contributes to non-relapse mortality in patients undergoing allo-HCT and auto-HCT, focusing especially on the pulmonary function. Our long term goal is to establish a disease risk predictive model, which will lead to preventive or anticipatory therapeutic interventions and improved outcomes of patients after allo-HCT and auto-HCT.

 

 

Team

Jesús Duque-Afonso, MD

Jesús Duque-Afonso, MD
Group leader
Hematologist/Oncologist
jesus.duque.afonso@uniklinik-freiburg.de

Miguel Waterhouse, PhD

Miguel Waterhouse, PhD
Postdoc
Biochemist
miguel.waterhouse@uniklinik-freiburg.de

Sandra Pennisi, M. Sc.

Sandra Pennisi, M. Sc.
Ph D Student
Biochemist
sandra.pennisi@uniklinik-freiburg.de

Gaia Gentile, M. Sc.

Gaia Gentile, M. Sc.
Ph D Student
Biotechnologist
gaia.gentile@uniklinik-freiburg.de

Heike Herzog

Heike Herzog
Medical Technical Assistant (MTA)
heike.herzog@uniklinik-freiburg.de

Bettina Berberich, M. Sc.

Bettina Berberich, M. Sc.
Research Assistant
Biologist
bettina.berberich@uniklinik-freiburg.de

Gila Mostufi-Zadeh-Haghighi

Gila Mostufi-Zadeh-Haghighi
MD Student
gila.mostufi@uniklinik-freiburg.de

Kristin Walther

Kristin Walther
MD Student
kristin.walther@uniklinik-freiburg.de

Sophie Ewald

Sophie Ewald
MD Student
sophie.ewald@uniklinik-freiburg.de

Patricia Grüninger

Patricia Grüninger
MD Student
patricia.grueninger@uniklinik-freiburg.de

Thilo Thanscheidt

Thilo Thanscheidt
MD Student
thilo.thanscheidt@uniklinik-freiburg.de

Paraschiva Pitu

Paraschiva Pitu
MD Student
paraschiva.pitu@uniklinik-freiburg.de

Mira Kusterer

Mira Kusterer
MD Student
mira.kusterer@uniklinik-freiburg.de

Ernesto Olcina Aguado

Ernesto Olcina Aguado
MD Student
ernesto.olcina.aguado@uniklinik-freiburg.de

Projects

Collaboration with Prof. Dr. O. Lohi (University of Tampere, Finland), Prof. Dr. M. Heinäniemi (University of Eastern Finland, Finland),  Prof. Dr. V. Wirta (Karolinska Institutet, Sweden) and Prof. Dr. J. Hauer, (University of Dresden, Germany)

Collaboration with Prof. Dr. Michael Lübbert (University of Freiburg, Germany)

Further Information

01/2020 - 12/2022 Research Grant from the German Research Foundation (DFG) for the project “Mechanisms of resistance to targeted therapy and chemotherapy in acute lymphoblastic leukemias”.

07/2019 - 06/2022 Research Grant from the ERA PerMed cofounded by the European Commission for the project “Genomics-based tools for personalized treatment to reduce chemotherapy burden in pediatric cancer (GEPARD)”.

01/2019 - 12/2020 Research Grant from Else Kröner-Fresenius-Stiftung for the project “Non-invasive monitoring of minimal residual disease and Graft-versus-Host Disease by circulating nucleic acids after allogeneic hematopoietic transplantation”.

01/2017 - 12/2017 Research Grant from the Research Committee (Forschungskommission) of the University of Freiburg for the project “Functional characterization of the TGFβ signalling pathway in acute lymphoblastic leukemia”.

Internal collaborations

  • Prof. Dr. J. Finke, University of  Freiburg Medical Center
  • Prof. Dr. M. Lübbert, University of  Freiburg Medical Center
  • Prof. Dr. R. Zeiser, University of  Freiburg Medical Center
  • Prof. Dr. M. Engelhardt, University of Freiburg Medical Center
  • PD Dr. R. Marks, University of Freiburg Medical Center
  • Dr. C. Miething, University of  Freiburg Medical Center
  • Prof. C. Dierks, University of  Freiburg Medical Center
  • Prof. Dr. C. Flotho, University of  Freiburg Medical Center
  • Dr. G. Ihorst, University of Freiburg Medical Center

External collaborations

  • Prof. Dr. M. Cleary, Stanford University, CA , USA
  • Prof. Dr. M. Bassik, Stanford University, CA, USA
  • Prof. Dr.  O. Lohi, University of Tampere and Tampere University Hospital, Finland
  • Prof. Dr. M. Heinäniemi, University of Eastern Finland, Finland
  • Prof. Dr. V. Wirta, Karolinska Institutet, Sweden
  • Prof. Dr. J. Hauer, University of Dresden, Germany
  • Prof. Dr. A. Borkhardt, University of Düsseldorf, Germany
  • Prof. Dr. G. Cario, University Medical Center Schleswig-Holstein  (Kiel), Germany
  • Prof. Dr. M. Schrappe, University Medical Center Schleswig-Holstein (Kiel), Germany
  • Dr. R. Sawarkar, Max Plack Institute, Freiburg, Germany

Graphic design

  • C. Duque-Afonso, cand. PhD, University of Göttingen, Germany

Top 10 publications

  1. Waterhouse M, Pennisi S, Pfeifer D, Deuter M, von Bubnoff N, Scherer F, Struessmann T, Wehr C, Duyster J, Bertz H, Finke J, Duque-Afonso J. (2020) Colon and liver tissue damage detection using methylated SESN3 and PTK2B genes in circulating cell-free DNA in patients with acute Graft-versus-Host disease. Bone Marrow Transplantation (in press).
  2. Duque-Afonso J, Ihorst G, Waterhouse M, Zeiser R, Wäsch R, Bertz H, Yücel M, Köhler T, Müller-Quernheim J, Marks R, Finke J. (2020) Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. Jun 26:1-11.
  3. Waterhouse M, Pfeifer D, Duque-Afonso J, Follo M, Duyster J, Depner M, Bertz H, Finke J. (2019) Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation. Clin Chem Lab Med. 57(5):641-647
  4. Duque-Afonso J, Waterhouse M, Pfeifer D, Follo M, Duyster J, Bertz H, Finke J.  (2018) Cell-free DNA characteristics and chimerism analysis in patients after allogeneic cell transplantation. Clin Biochem.;52:137-141.
  5. Duque-Afonso J, Lin CH, Han K, Morgens DW, Jeng EE, Weng Z, Jeong J, Wong SHK, Zhu L, Wei MC, Chae HD, Schrappe M, Cario G, Duyster J, Xiao X, Sakamoto KM, Bassik MC, Cleary ML. (2018). CBP Modulates Sensitivity to Dasatinib in Pre-BCR+ Acute Lymphoblastic Leukemia. Cancer research. 2018; 78(22):6497-6508. 
  6. Duque-Afonso J, Ihorst G, Waterhouse M, Zeiser R, Wäsch R, Bertz H, Müller-Quernheim J, Finke J, Marks R, Prasse A.  (2018). Impact of lung function on bronchiolitis obliterans syndrome and outcome after allogeneic hematopoietic cell transplantation with reduced intensity conditioning. Biology of Blood and Marrow Transplantation;24(11):2277-2284.
  7. Duque-Afonso J, Lin CH, Han K, Wei MC, Feng J, Kurzer JH, Schneidawind C, Wong SH, Bassik MC, Cleary ML. (2016) E2A-PBX1 Remodels Oncogenic Signaling Networks in B-cell Precursor Acute Lymphoid Leukemia. Cancer Res.;76(23):6937-6949.
  8. Duque-Afonso J, Feng J, Scherer F, Lin CH, Wong SH, Wang Z, Iwasaki M, Cleary ML. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia. Journal of Clinical Investigation. 2015;125(9):3667-80.
  9. Duque-Afonso J, Ihorst G, Wäsch R, Bertz H, Müller-Quernheim J, Finke J, Prasse A, Marks R. Identification of risk factors for bronchiolitis obliterans syndrome after reduced toxicity conditioning before hematopoietic cell transplantation. Bone Marrow Transplant. 2013; 48(8):1098-103.
  10. Duque-Afonso J, Yalcin A, Berg T, Abdelkarim M, Heidenreich O, Lübbert M.. The HDAC Class I specific inhibitor Entinostat (MS-275) effectively relieves epigenetic silencing of the LAT2 gene mediated by AML1/ETO. Oncogene 2011; 30(27): 3062-72.

Review articles and book chapters

  1. Duque-Afonso J, Cleary ML.  The AML Salad Bowl. Cancer Cell. 2014;25(3):265-7.

Complete List of Published Work in: