Research projects

When applying for the BSIO, students do not apply for specific projects, but for admission to the school in general. However, applicants are requested to choose 5 BSIO faculty members in whose research focus they are interested  in (representing potential supervisors) as part of their application (please refer to Faculty members for profiles of all faculty members including their CV and research interest).

The applicants who are invited to Berlin will have the chance to meet their preferred faculty members (as well as faculty members who would like to meet them) for personal interviews in order to find a supervisor. 

Students admitted to the BSIO will develop their research projects together with their advisors.

However, to give applicants an idea of the potential projects that may be pursued at the BSIO and to specify the research projects of the faculty members and groups involved in the BSIO, a list of potential projects is given below. Applicants are requested to read this information before choosing potential superviors within their application at the online portal.

The projects listed are of an exemplary nature only; the (dropdown) list of all supervisors recruiting students can be found in the online application tool only (at the points "first to fifth supervisor choice).

The majority of projects are suitable for PhD as well as MD candidates.

Potential research projects

Prof. Helmut Anheier

Potential PhD projects:

  • The governance of cancer treatment
  • Societal perceptions of cancer research
  • Alternative business models for cancer research
  • The sociology of cancer prevention and awareness programmes
  • Advanced training of nurses in cancer treatment
  • Managing interdisciplinary skills and training in cancer treatment

Prof. Claudia Baldus

Scope of the project: Within the German wide DKTK consortium (of the DKFZ in Heidelberg) we will explore genotype based drug response signatures in leukemia.

Background: Preparing a personalized clinical trial, the proposed consortium integrates detailed tumor cell profiling with preclinical in-vitro and in-vivo drug testing to address individual pathway dependencies, using acute lymphoblastic leukemia (ALL) as model disease. We set up an interconnected pipeline of genotype-directed preclinical drug response testing and have established an ALL specific gene panel to prospectively screen relapsed ALL patient samples; this will facilitate to identify affected pathways and direct in-vitro assessments of drug response. Functional studies for target validation, identification of response biomarkers as well as drug resistance mechanisms will flank these studies. The final aim is to implement effective drug combinations specific to defined genotypes into the clinical setting. For this, ALL patients will be prospectively genotyped using this ALL gene panel and integration will be based on the established genotype-drug response signatures to subsequently enroll ALL patients with minimal residual disease into individualized German ALL study group (GMALL) trials.

Our group is highly active and focused on the molecular dissection on acute leukemia using a wide spectrum of experimental methods. In addition, we have access to large sample banks and clinical data sets within the German wide study groups.

(https://haema-cbf.charite.de/forschung/wissenschaftliche_arbeitsgruppen/ag_baldus/)

For this project we are seeking at the CharitéCentrum14, Department of Hematology, Oncology and Tumor immunology at the Campus Benjamin Franklin from 01.02.2017 for 3 years a PhD student.

 The specific aims will be to explore genetic lesions (by targeted NGS) and to perform genotype directed drug response assays of on leukemic cell lines, PDX samples, primary cells in mono and co-culture systems.

 Required Experience include:

· Comprehensive knowledge NGS derived data sets including WES, RNAseq, panel NGSs

· Expertise in molecular genetics and molecular biology including DNA; RNA, CHIP, FACS, cell culture, cytotoxicity screens, PCR, RT-PCR, cloning, transfection, knock-down.

· Team player, focused individual with a strong work ethic and great attention to detail.

· Must exhibit excellent communication skills and a broad knowledge able to distil and relay complex scientific concepts to a variety of members within the consortium.

Ability to exercise judgment within broadly defined practices and policies in selecting methods, techniques, and evaluation criteria for obtaining results

--> Please submit your application via the BSIO online tool choosing Prof. Baldus as your preferred supervisor if you would like to apply for this project.

Prof. Walter Birchmeier

Potential PhD or MD projects:

 

Signaling and Metastasis of Stem and Cancer Stem Cells

Conditional LOF and GOF mutations of β-catenin in mice were used to study canonical Wnt signal­ing in stem and cancer stem cells. Wnt/β-catenin signaling was examined in metastasis of colon cancer. Signaling of Met and other receptor tyrosine kinases through Gab1 and Shp2 controls organ development.

 

Wnt/ß-catenin, BMP and Met

β-catenin GOF and BmpR LOF mutations created rapid tumors in salivary glands and maintained selfrenewal of cancer stem cells by  Histone 3K4 trimethylation. GOF mutations of β-catenin and Met resulted in basal-like mammary gland tumors: Wnt signaling stimulates self-renewal and Met suppress differentiation of cancer stem cells. Wnt and Met inhibitors block tumor formation. The Wnt/Met signature predicts survival of patients with Basal and HER2 breast cancer.

 

Inhibitors of Shp2 and ß-catenin

GS-493 is 20-fold more active than PHPS1 and interferes with MMTV-PyMT mammary gland tu­mor and mammosphere formation, and with human lung tumor cell xenografts. LF3 disrupts the association of β-catenin and TCF4, inhibits Wnt signaling, reduces cell migration, and blocks spheroids of colon cancer stem cells.

 

Research aims & perspectives

We will unravel the function of genes that control self-renewal and differentiation of mammary and salivary gland cancer stem cells. MicroRNAs that are regulated during selfrenewal and differentiation will be identifiedWe found that several microRNAs were down-regulated in the cancer stem cells following ICG-001 treatment, like mir-210, while others were upregulated, like let-7. Candi­date genes and microRNAs will be functionally examined by siRNA and Antagomir technology or overexpression in cultured stem cells. Functional screening for other signaling networks that are regulated by Wnt/Met/Bmp signaling will be performed. The phosphor proteome associated with different stages of cancer development will be defined.

 

The failure to specifically target cancer stem cells is a major hurdle in current tumor treatment. We will test combinations of Wnt and Met inhibitors to eradicate cancer stem cells in model systems. We will also characterize Xenograft models to identify human cancers types that express our signaling networks. We will improve our Wnt and Shp2 inhibitors by medicinal chemistry.

Prof. Thomas Blankenstein

Potential PhD or MD project:

  • T cell receptor gene therapy against therapy-induced Bcr-Abl mutations in drug-resistant CML. 

 

 

Prof. Nils Blüthgen

Potential PhD or MD project:

  • The role of feedbacks and network topology on drug sensitivity for targeted inhibitors in the EGF-receptor pathway
Prof. Volker Haucke

We appreciate applications of research-experienced, highly motivated biomedical undergraduates to enter a PhD project within one of the following scientific areas:

  • Endosomal sorting of growth and differentiation factor receptors in cell division and growth control
  • Phosphoinositide metabolizing enzymes and their role in cancer
  • Proteomic analysis of the clathrin CHC17 and CHC22 interactomes during cell division

The projects will combine high-end live imaging with genetic, proteomic, biochemical, and cell biological approaches.

Prof. Michael Hummel

The application of research oriented and highly motivated biomedical undergraduates are very welcome to enter a PhD or MD project within one of the following scientific areas:

  • Molecular mechanisms in malignant lymphomas
  • Epigenetic defects in B-cell and T-cell lymphomas
  • Transcription factor binding studies (e.g. MYC)
  • Whole genome and whole transcriptom studies
  • Comprehensive analysis of B-cell and T-cell repertoire hematological disorders
Dr. Stefan Kempa

Potential PhD or MD project:

Metabolic reprogramming is a key step in oncogenic transformation including the activation of energy- and anabolic-metabolism. Thus, differentiated cells reenter the cell cycle and proliferate. The central metabolism is the ultimate source of energy and building blocks enabling growth and proliferation.

We have further developed gas chromatography coupled mass spectrometry (GC-MS) to measure the dynamics of the central metabolism in high resolution. Therefore we apply stable isotope labeled substrates to cells and determine their incorporation rates within a very short time using pulsed stable isotope resolved metabolomics (pSIRM) - a method which was developed by our group. pSIRM for example enables to directly compare the dynamics of glycolysis and glutaminolysis and to track the individual carbon routes within the cell.

Metabolomics in combination with quantitative proteomics (SILAC and phospho-proteomics) enables to decode complex metabolic phenotypes (Mastrobuoni et al. 2012).Within the proposed project we aim to further explore the therapeutic window introduced by the deregulated MYC oncogene (Liu et al. 2012).

Liu L. et al. (2012) Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature 483(7391):608-12.

Mastrobuoni G. (2012) Proteome dynamics and early salt stress response of the photosynthetic organism Chlamydomonas reinhardtii. BMC Genomics 13(1):215.

Prof. Ulf Leser

We seek enthustic and skillful PhD candidates with a solid background in cancer biology and in bioinformatics / systems biology for a project on in-silico reconstructing the human core regulatory network, using a mixture of experimental and literature-derived data. Applications should bring at least basic knowledge in statistical data analysis and machine learning. The project will be co-hosted by Prof. Nils Blüthgen, Medical Systems Biology, Charite Berlin.

 

Prof. Jörg Rademann

Potential PhD (or MD) projects:

- Development of fragment-based inhibitors of arginase - a target in immunotherapy of cancer

- Small-molecule ligands of the STAT5 SH2 domain and their effects in leukemic cells

- Inhibitors of protein tyrosine phosphatases as chemical tools in cancer cells

The PhD projects in Prof. Rademann's group will be offered in collaboration (and co-supervision) with Prof. Gerard Wolber and Prof. Britta Siegmund.

Dr. Angela Relogio

We seek higly motivated students with a background in physics, mathematics, informatics or biology, to work in interdisciplinary projects involving wet lab work, mathematical modelling and bioinformatics. Our group cooperates with several groups within the BSIO School and also with institutes outside Berlin such as the European Molecular Biology Laboratory (EMBL) in Heidelberg, the Institute for Molecular Medicine (IMM) in Lisbon and the Centre for Genomic Regulation (CRG) in Barcelona. We have open positions for both wetlab and computational projects. Available projects include mathematical modelling of the circadian clock and circadian networks in a cancer context and analysis of alternative splicing switches in tumorigenesis. We are looking forward for your application.

Prof. Clemens Schmitt

Perspectives for Future PhD or MD Thesis Projects:

  • Metabolic defects and anticancer drug responsiveness
  • Cellular senescence and host immune interaction
  • Translating various “omics” data levels into underlying pathway information (co-hosted by Prof. Ulf Leser, Dep. of Data Management and Bioinformatics, Humboldt Universität zu Berlin)
  • Modeling societal stress responses as evolution-conserved evasion strategies in cancer – a transdisciplinary (theoretical and „wet bench“) approach (co-hosted by Prof. Miranda Schreurs, Dep. of Political and Social Sciences, and Prof. Rupert Mutzel, Institute of Biology, both Freie Universität Berlin)