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Julia Hauer - Pediatric Oncology/Hematology
Research Focus
Pediatric oncology program at TranslaTUM is composed of two pillars (1) prevention of childhood cancer focusing in acute leukemia and (2) translational cellular immunotherapy and oncolytic virotherapy against pediatric sarcoma.
Prevention of cancer in children and young adults is a high goal. Cure rates of cancer are extremely high in children (80%) but disease and therapy related morbidity impact individuals quality of life and the health care system for decades. Thus our group aims at identifying children and young adults with a genetic risk for cancer and approaches, which allow modulation of the host immune response towards environmental challenges to prevent cancer. We focus on acute leukemia, the most prevalent cancer in childhood. For this purpose, we have collected an in-depth characterized cohort of n=150 transgeneration child-parent trios of children with cancer comprising clinical and genetic data. This cohort will be now extended at pediatric oncology TUM in collaboration with NCT Dresden. Combining integrated bioinformatic analysis and molecular functional assays both in-vitro as well as in-vivo, we aim to pinpoint novel signalling pathways predisposing to cancer. We further investigate the role of environmental challenges and early immune training in transgenic murine models. Training of the innate and adaptive immune system is carried out with the aim to pave the way for an early preventive strategy against childhood leukemia. This work is conducted in the context of an ERC and DKH excellence strategy funding.
Translational cellular immunotherapy and oncolytic virotherapy against pediatric sarcoma is the second research pillar. Especially advanced stages of sarcoma have a poor prognosis in children despite extensive therapy. We demonstrated that infusion of unspecific donor lymphocytes after allogeneic stem cell transplantation has the capacity to induce tumour control in paediatric sarcoma patients emphasizing the need to identify tumour-specific cellular approaches. In our hands, pediatric sarcoma has become susceptible to immunotherapy using peptide/HLA-A2 tumour specific allo-restricted wildtype- and retrovirally T cell receptor transduced T cells directed against several Ewing sarcoma (EwS) associated tumor antigens in vitro and in a preclinical mouse model. Adoptive T-cell transfer led to in vivo persistence without inducing GvHD and T cells homed to affected bone marrow and were associated with partial tumour regression (Heisenberg program - PD Dr Thiel). A BMBF granted phase I clinical study using oncolytic virotherapy in combination with CDK4/6 inhibition and immune-checkpoint inhibition will commence in 2023 in our clinic (in cooperation with Per Sonne Holm and Roman Nawroth - Department for Urology, Klinikum rechts der Isar).
Julia Hauer studied medicine at the Ludwig-Maximilians-Universität München and defended her MD thesis with summa cum laude in immunology. As a postdoc her research focused on gene therapy at the Hôpital Necker, Paris. She continued her clinical training and subspecialisation as pediatric hemato-oncologist at the Heinrich-Heine University Düsseldorf, where she did her habilitations. Before joining TUM, Julia Hauer was associated professor and head of pediatric hematology and oncology at TU Dresden as well as group leader at NCT Dresden.
Julia Hauer investigates the importance of genetic predisposition for the development of childhood cancer with a specific focus on acute leukemia. In addition she investigates the role of environmental exposure in childhood and how the immune system can be modulated to avoid acute leukemia. The aim is to offer preventive measures for children with a risk for cancer. Beyond Julia Hauer is interested in the design of novel therapeutic options and their implementation in clinical treatment.
- ERC starting grant (ERCStg 85222 “PreventALL) (2019)
- German Cancer Aid Excellence Funding for established scientists (70114539)
- Scholarship Leopoldina National Academie of Science, Halle, Germany (BMBF-LPD99018-149) (2006)
Hauer, J., Fischer, U., Borkhardt, A. (2021). Toward prevention of childhood ALL by early-life immune training. Blood 138, 1412-1428.
Vicente-Dueñas, C., Janssen, S., Oldenburg, M., Auer, F., González-Herrero, I., Casado-García, A., Isidro-Hernández, M., Raboso-Gallego, J., Westhoff, P., Pandyra, A.A., Hein, D., Gössling, K.L., Alonso-López, D., De Las Rivas, J., Bhatia, S., García-Criado, F.J., García-Cenador, M.B., Weber, A.P.M., Köhrer, K., Hauer, J., Fischer, U., Sánchez-García, I., Borkhardt, A. (2020). An intact gut microbiome protects genetically predisposed mice against leukemia. Blood 136, 2003-2017.
Rodríguez-Hernández, G., Opitz, F.V., Delgado, P., Walter, C., Álvarez-Prado, Á.F., González-Herrero, I., Auer, F., Fischer, U., Janssen, S., Bartenhagen, C., Raboso-Gallego, J., Casado-García, A., Orfao, A., Blanco, O., Alonso-López, D., Rivas, J.D.L., Tena-Dávila, S.G.D., Müschen, M., Dugas, M., Criado, F.J.G., Cenador, M.B.G., Vicente-Dueñas, C., Hauer, J., Ramiro, A.R., Sanchez-Garcia, I., Borkhardt, A. (2019). Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID. Nature Communications 10,
Lin, M., Nebral, K., Gertzen, C.G.W., Ganmore, I., Haas, O.A., Bhatia, S., Fischer, U., Kuhlen, M., Gohlke, H., Izraeli, S., Trka, J., Hu, J., Borkhardt, A., Hauer, J., Auer, F. (2019). JAK2 p.G571S in B-cell precursor acute lymphoblastic leukemia: a synergizing germline susceptibility. Leukemia 33, 2331-2335.
García‐Ramírez, I., Bhatia, S., Rodríguez‐Hernández, G., González‐Herrero, I., Walter, C., González De Tena‐Dávila, S., Parvin, S., Haas, O., Woessmann, W., Stanulla, M., Schrappe, M., Dugas, M., Natkunam, Y., Orfao, A., Domínguez, V., Pintado, B., Blanco, O., Alonso‐López, D., De Las Rivas, J., Martín‐Lorenzo, A., Jiménez, R., García Criado, F.J., García Cenador, M.B., Lossos, I.S., Vicente‐Dueñas, C., Borkhardt, A., Hauer, J., Sánchez‐García, I. (2018). Lmo2 expression defines tumor cell identity during T‐cell leukemogenesis. The EMBO Journal 37, e98783.
Bhatia, S., Diedrich, D., Frieg, B., Ahlert, H., Stein, S., Bopp, B., Lang, F., Zang, T., Kröger, T., Ernst, T., Kögler, G., Krieg, A., Lüdeke, S., Kunkel, H., Rodrigues Moita, A.J., Kassack, M.U., Marquardt, V., Opitz, F.V., Oldenburg, M., Remke, M., Babor, F., Grez, M., Hochhaus, A., Borkhardt, A., Groth, G., Nagel-Steger, L., Jose, J., Kurz, T., Gohlke, H., Hansen, F.K., Hauer, J. (2018). Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response. Blood 132, 307-320.
Martín-Lorenzo, A., Auer, F., Chan, L.N., García-Ramírez, I., González-Herrero, I., Rodríguez-Hernández, G., Bartenhagen, C., Dugas, M., Gombert, M., Ginzel, S., Blanco, O., Orfao, A., Alonso-López, D., Rivas, J.D.L., García-Cenador, M.B., García-Criado, F.J., Müschen, M., Sánchez-García, I., Borkhardt, A., Vicente-Dueñas, C., Hauer, J. (2018). Loss of Pax5 Exploits Sca1-BCR-ABLp190 Susceptibility to Confer the Metabolic Shift Essential for pB-ALL. Cancer Research 78, 2669-2679.
Martín-Lorenzo, A., Hauer, J., Vicente-Dueñas, C., Auer, F., González-Herrero, I., García-Ramírez, I., Ginzel, S., Thiele, R., Constantinescu, S.N., Bartenhagen, C., Dugas, M., Gombert, M., Schäfer, D., Blanco, O., Mayado, A., Orfao, A., Alonso-López, D., Rivas, J.D.L., Cobaleda, C., García-Cenador, M.B., García-Criado, F.J., Sánchez-García, I., Borkhardt, A. (2015). Infection Exposure Is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of Pax5-Inherited Susceptibility. Cancer Discovery 5, 1328-1343.
Hauer, J., Mullighan, C., Morillon, E., Wang, G., Bruneau, J., Brousse, N., Lelorc'H, M., Romana, S., Boudil, A., Tiedau, D., Kracker, S., Bushmann, F.D., Borkhardt, A., Fischer, A., Hacein-Bey-Abina, S., Cavazzana-Calvo, M. (2011). Loss of p19Arf in a Rag1−/− B-cell precursor population initiates acute B-lymphoblastic leukemia. Blood 118, 544-553.
Hacein-Bey-Abina, S., Hauer, J., Lim, A., Picard, C., Wang, G.P., Berry, C.C., Martinache, C., Rieux-Laucat, F., Latour, S., Belohradsky, B.H., Leiva, L., Sorensen, R., Debré, M., Casanova, J.L., Blanche, S., Durandy, A., Bushman, F.D., Fischer, A., Cavazzana-Calvo, M. (2010). Efficacy of Gene Therapy for X-Linked Severe Combined Immunodeficiency. New England Journal of Medicine 363, 355-364.