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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Duque lab

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 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 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 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.

2.1. Characterization of oncogenic signaling pathways involved in pathogenesis and drug resistance in pre-B cell acute lymphoblastic leukemia (pre-B ALL)

2.1. Characterization

Collaboration with Prof. Dr. M. Cleary and Prof. Dr. M. Bassik (Stanford University, CA, USA)


2.2. Genomics-based tools for personalized treatment to reduce chemotherapy burden in pediatric cancer (GEPARD)

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)


2.3. Identification of factors for GvHD and relapse risk assessment after allogeneic hematopoietic cell transplantation

Collaboration with Prof. Dr. J. Finke (University of Freiburg, Germany).


2.4. Understanding transcriptional regulation by chromatin-modifying enzymes in acute myeloid leukemia (AML)

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


Miguel Waterhouse, PhD
Sandra Pennisi, M. Sc.
Sandra Pennisi, M. Sc.

Research assistant
Biochemist

sandra.pennisi@uniklinik-freiburg.de

Bettina Berberich, M. Sc.

Research assistant
Biologist

bettina.berberich@uniklinik-freiburg.de

Gila Mostufi-Zadeh-Haghighi
Kristin Walther
Sophie Ewald
  • 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".

Top 10 publications

  1. 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.
  2. 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.
  3. 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.
  4. Zhu L, Li Q, Wong SH, Huang M, Klein BJ, Shen J, Ikenouye L, Onishi M, Schneidawind D, Buechele C, Hansen L, Duque-Afonso J, Zhu F, Mas Martin G, Gozani O, Majeti R, Kutateladze TG, Cleary ML. (2016) ASH1L links histone H3 lysine 36 di-methylation to MLL leukemia. Cancer Discov. 6(7):770-83.
  5. Buechele C, Breese EH, Schneidawind D, Lin CH, Jeong J, Duque-Afonso J, Wong SH, Smith KS, Negrin RS, Porteus M, Cleary ML. (2015) MLL leukemia induction by genome editing of human CD34+ hematopoietic cells. Blood;126(14):1683-94.
  6. 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.
  7. Wong SH, Goode, DL, Iwasaki M, Wei MC, Kuo HP, Zhu L, Schneidawind D, Duque-Afonso J, Weng Z, and Cleary ML. The H3K4-methyl epigenome regulates leukemia stem cell oncogenic potential. Cancer Cell 2015;28(2):198-209.
  8. Kuo HP, Wang Z, Lee DF, Iwasaki M, Duque-Afonso J, Wong SH, Lin CH, Figueroa ME, Su J, Lemischka IR, Cleary ML. Epigenetic roles of MLL oncoproteins are dependent on NF-κB Cancer Cell. 2013; 24(4):423-37.
  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:

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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
  • PD Dr. 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. 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
Group leader

Jesús Duque-Afonso, MD

jesus.duque.afonso@uniklinik-freiburg.de

Telefon0761 270 71822

Adresse

Universitätsklinikum Freiburg
Klinik für Innere Medizin I
Hämatologie/Onkologie
Hugstetter Str. 55

D-79106 Freiburg