11 PhD positions for applicants from the natural sciences


Available Positions

The i-Target doctoral program offers financial support for 11 PhD positions for applicants from the natural sciences for the following projects A to K.

Applications are only possible online using the following link: portal.graduatecenter-lmu.de/i-target. The application portal will be open from may May 19th through June 20th 2014. For any inquiries concerning the program or the application process, please contact the i-Target staff: itarget@med.uni-muenchen.de. Please note that applications submitted by email will not be considered.

Research Area 1: Targeted cellular therapy

  • A: Arming tumor specific T cells with CC motive receptors

    Principle investigators: PD Dr. Sebastian Kobold and Prof. Stefan Endres

    Brief description: Adoptive T cell therapy is one of the most promising approaches for the treatment of cancer. A major limitation is the infiltration or homing of the transferred T cells to the tumor site. The aim of this PhD-project will be to overexpress defined chemokine receptors on tumor-specific T cells to enhance the efficacy of adoptive T cell therapy. The methods will comprise a wide range of cellular and immunological methods and will include in vivo experiments.

    Homepage: www.klinikum.uni-muenchen.de/Abteilung-fuer-Klinische-Pharmakologie/de

  • B: Enhancing T cell therapy through activating receptors

    Principle investigators: PD Dr. Sebastian Kobold and Prof. Stefan Endres

    Brief description: Tumors mount an effective immunosuppressive milieu to prevent immune cells to efficiently recognize tumor cells and suppress their activity. The aim of this Ph. D. project will be to overexpress in-house engineered activating receptors to enhance the efficacy of adoptive T cell therapy. The methods will comprise a wide range of cellular and immunological methods and will include in vivo experiments.

    Homepage: www.klinikum.uni-muenchen.de/Abteilung-fuer-Klinische-Pharmakologie/de

  • C: Engagement of T cells through bispecific antibodies

    Principle investigators: PD Dr. Sebastian Kobold and Prof. Stefan Endres

    Brief description: Bispecific antibodies have the great advantage of specific targeting of two different antigens, allowing for both immune and tumor cell binding. The aim of this Ph. D. project will be to design and use new bispecific antibodies to enhance the efficacy of adoptive T cell therapy. The methods will comprise a wide range of cellular and immunological methods and will include in vivo experiments.

    Homepage: www.klinikum.uni-muenchen.de/Abteilung-fuer-Klinische-Pharmakologie/de

  • D: Therapeutic vaccines and immune check point blockade in leukemia

    Principle investigator: PD Dr. Marion Subklewe; Department of hematology / oncology, University Hospital of the Ludwig-Maximailians-Universität, Munich, Germany

    Brief description: We have documented the generation of superior dendritic cells (DCs) from monocytes of AML patients using a fast, TLR ligand-containing maturation cocktail. Based on our preclinical data, we have initiated a proof-of-concept trial using RNA-transfected DCs for postremission therapy in AML. Therapeutic vaccinations induced cellular immune responses may be hampered by upregulation of immune inhibitory molecules (“immune checkpoint markers”) on target cells.

    The aim of this Ph.D. project is to identify immuninhibitory pathways relevant in AML as mechanisms of immune escape and as therapeutic targets. The therapeutic potential of checkpoint inhibitors and other immunmodulatory drugs will be assessed in vitro and in collaboration also in an in vivo AML mouse model. The methods will comprise a wide range of cellular and immunological methods and will optionally include in vivo experiments.

    Homepage: www.klinikum.uni-muenchen.de/Medizinische-Klinik-und-Poliklinik-III/de/team/oberaerzte/subklewe_m

 

Research Area 2: Targeted immunomodulatory therapy

  • E: Development of innovative multispecific antibody derivatives for the specific recruitment of immune effector cells to tumor cells

    Principle investigator: Prof. Dr. rer. nat. Karl-Peter Hopfner

    Brief description: The project will involve a combination of protein engineering, protein biochemistry and functional studies (cell culture, cell lysis assays, FACS). In collaboration with other iTarget members, the final goal of the PhD thesis is to test the efficacy in mouse models.

    Homepage: www.hopfner.genzentrum.lmu.de

  • F: Identifying novel immunological epitopes for immunotherapy of acute myeloid leukemia.

    Principle investigators: Prof. Dr. Christoph Klein, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University, Munich, Germany.

    Brief description: In this Phd project we plan to develop a research pipeline to discover novel therapeutic targets for AML by deciphering key factors controlling myeloid cell differentiation. Thus we wish to study the potential role of novel targets in murine leukemia cells as well as the identification of novel pathways via genome-wide analysis of rare children with monogenetic diseases. We plan to design monoclonal antibodies and chimeric T-cell receptors recognizing specific membrane-bound proteins and anticipate that immune-targeting will selectively eliminate myeloid cells. Immune-effectors will be systematically assessed in vitro and in vivo for their capacity to recognize and kill myeloid leukemia cells. The methods will comprise a wide range of cellular, immunological and biochemical methods as well as in vivo experiments.

    Homepage: www.klein.genzentrum.lmu.de

  • G: Induction of anti-leukemic T-cell responses by bystander killing of CD33+ myeloid-derived suppressor cells via a CD33/CD3-bispecific BiTE® antibody construct

    Principle investigators: Prof. Dr. Andreas Mackensen and PD Dr. Dimitrios Mougiakakos, Department of Hematology and Oncology, University Hospital, Friedrich-Alexander-University, Erlangen, Germany

    Brief description: In recent years myeloid derived suppressor cells (MDSCs) have emerged as a key cell subset that promotes tumor immune escape. Strategies to overcome MDSC-mediated immune suppression hold promise to improve efficacy of modern immunotherapies. The aim of this PhD project is to (1) characterize MDSCs in patients with acute myeloid leukemia (AML) in order to (2) target them with a novel so-called CD33/CD3 bi-specific antibody (AMG330) showing a high anti-leukemic activity. In doing so we hope elicit two critical hits against AML. The methods utilized in this translational project will comprise a broad variety of cellular, molecular, and immunological techniques.

    Homepage: www.medizin5.uk-erlangen.de/en/research-teaching

 

Research Area 3: Targeted immunomodulatory therapy

  • H: Harnessing immune responses in hematological malignancies by redox remodeling

    Principle investigators: PD Dr. Dimitrios Mougiakakos and Prof. Dr. Andreas Mackensen, Department of Hematology and Oncology, University Hospital, Friedrich-Alexander-University, Erlangen, Germany

    Brief description: Emerging evidence suggest that tumor-associated oxidative stress weakens the patients’ immune system and thereby contributes to tumor immune escape and attenuates the efficacy of immune based therapies. In this PhD project we aim to (1) evaluate oxidative stress-induced immune alterations in patients with leukemia and to develop strategies for pharmacologically (2) antagonizing this metabolic condition and for (3) enhancing the resilience of immune cells towards it. The ultimate goal is to boost intrinsic anti-tumor immune responses and to increase the efficacy of immune based therapies. The methods utilized in this translational project will comprise a broad variety of cellular, immunological, and metabolic techniques.

    Homepage: www.medizin5.uk-erlangen.de/en/research-teaching

  • I: Combination of radiotherapy with Hsp90 inhibition to enhance the extent and the immunogenicity of tumor cell death for the treatment of sarcoma

    Principle investigators: Prof. Kirsten Lauber, Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany

    Brief description: The induction of immunogenic forms of cell death by specific radiotherapeutic regimes appears to be a promising approach for the stimulation of innate and adaptive anti-tumor immune responses. The aim of this PhD project is to explore, whether Hsp90 inhibition in combination with radiotherapy can enhance the extent as well as the immunogenicity of sarcoma cell death, and whether this can contribute to the stimulation of anti-sarcoma immune responses. To this end, various molecular, cell biological, and immunological methods will be employed, including in vivo experiments.

    Homepage: www.klinikum.uni-muenchen.de/Klinik-und-Poliklinik-fuer-Strahlentherapie-und-Radioonkologie/de/forschung/molek_onkologie/index.html

  • J: Card9 signaling in anti-tumor immunity

    Principle investigator: Prof. Jürgen Ruland, Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München

    Brief description: T cell activation is controlled by signals from antigen-presenting cells (APCs). APCs express multiple distinct pattern recognition receptors that can respond to specific innate immune stimuli and trigger unique signaling pathways that can prime T cell responses in a differential manner. The downstream adapter protein Card9 is absolutely critical for this process. Using in vitro and in vivo techniques, the PhD student will characterize the role of Card9 in the induction of T cell responses and tumor immunity. Another major aim of the project is to investigate the role of innate immune effectors on tumor growth and survival and their role in the tumor environment.
    Homepage: www.klinchem.med.tum.de

  • K: Targeting myeloid-derived suppressor cells (MDSC) in pancreatic cancer with ligands of RIG-I like helicases (RLH)

    Principle investigator: Prof. Max Schnurr, Division of Clinical Pharmacology, University Hospitals, Ludwig-Maximilians-Universität, Munich, Germany

    Brief description: Pancreatic cancer is characterized by an immunosuppressive network involving immature myeloid cells, so called MDSCs. Reprogramming MDSCs from an immunosuppressive (M2) towards an immunogenic (M1) phenotype is a novel therapeutic approach for breaking immunosuppression in tumors. The aim of this PhD project will be to assess the influence of immune stimulatory RNA species that activate the cytosolic helicase RIG-I on MDSC functional profiles, both tumor-promoting and -inhibitory. The methods will comprise a wide range of cellular and immunological methods and will include in vivo experiments in murine pancreatic carcinoma models.

    Homepage: www.klinikum.uni-muenchen.de/Abteilung-fuer-Klinische-Pharmakologie/de