Ao. Prof.-Mag. Dr. Wolfgag Mikulits
Dept of Internal Medicine I
Institute of Cancer Research
1090 Vienna, Austria
Phone: +43-1- 40160 57527
Cancer Research is a multidisciplinary scientific field. Basic cancer research employs in vitro and in vivo models to identify tumor specific regulatory mechanisms and targets for cancer therapy. It investigates the cellular mechanisms of carcinogens to understand cancer causes and analyses exogenous and endogenous factors contributing to tumor development. The results are applied to develop diagnostic procedures, new therapies, and preventive strategies (translational research). Clinical oncology comprises the development and evaluation of new therapeutics and diagnostic procedures.
The thesis program Malignant Diseases aims to encompass these areas of cancer research to provide students with a profound theoretical background in cancer research as well as excellent practical skills. The participating groups are engaged in international research projects in the areas of basic tumor biology as well as translational and clinical oncology and hematology. They use up to date molecular and cell biological methodology as detailed below.
Medical Biology, Karner-Hanusch
experimental tumor induction
Grasl-Kraupp, Huber, Knasmüller
Cancer Research, Dpt. Internal Medicine 1
Medical Biology, Berger
xenobiotic- / carcinogen metabolism
Huber, Knasmüller, Parzefall
gene expression profiles
Berger, Chiba, Mikulits, Schreiber
genotoxicity assays (e.g. Ames, COMET)
Dpt. Internal Medicine 1, specifically Steger
Dpt. Internal Medicine 1, Cancer Research, Med. Biology
methylation specific PCR
Dpt. Internal Medicine 1, Medical Biology
reporter gene expression
Dpt. Internal Medicine 1, Cancer Research, Med. Biology
stable and transient transfection
Berger, Marian, Mikulits
Projects offered for PhD will cover the following thematic fields:
? Signaling pathways as therapeutic targets
Progressive deregulation of growth control is a central characteristic of tumor development. In a step-by-step process tumor cells develop characteristic changes in tumor-specific signaling pathways that can be targeted by therapeutic intervention. This has already been done with varying success for different signaling molecules (erbB2, bcr-abl, EGF-receptor). With regard to numerous emerging new therapy targets, the necessity arises to characterize the underlying molecular mechanism with regard to cellular functions and interaction partners of the target. Groups in the thesis program Malignant Diseases use diverse in vitro models for both hematological malignancies and solid tumors. Genes of interest are introduced in suitable cell lines by different methods of transfection including viral vectors. Gene knock-down is achieved by anti-sense nucleotides and siRNA technology. A SCID mouse facility is available to study tumor xenograft growth. A strong focus on translational research at the Department of Medicine 1 will introduce targeted therapeutics into clinical testing.
? Tumor specific gene expression and regulation
In malignant cells gene expression is altered by both genetic and epigenetic mechanisms. Some transcription factors are proto-oncogene and over-expressed in malignant cells. In addition promoter activity is altered by tumor-specific patterns of DNA methylation and / or histone acetylation. Up to date methodology is available from the participating groups that permit whole genome analysis of gene expression patterns (Affimetrix), as well as expression of small groups of genes (dedicated micro arrays) and individual genes on the mRNA (RT-PCR) and protein level (western blot, immunocytochemistry and immunohistochemistry) and lastly methylation patterns (methylation specific PCR).
? Molecular mechanisms of tumor progression and metastasis
Malignant progression permits tumor cells the acquisition of those phenotypical traits that enable tumor vascularization, invasiveness and metastasis. This involves interactions with the connective tissue, endothelium and immune cells, matrix degradation and epithelial-mesenchymal transition (EMT). Participating groups have available cellular models of the cell types involved, experimental tumor models and access to human tissue specimen. They use whole genome micro arrays, RT-PCR, karyotyping and FISH and functional assays to identify proteins and signaling pathways involved.
? Cancer Causes: Risk factors and Prevention
Malignant tumors develop through a time consuming process by which both genetic and epigenetic alterations accumulate and cooperate to produce tumor growth and a transformed phenotype. This process can be initiated and driven by exogenous (chemicals, radiation) as well as endogenous (hormones, inflammation) causes. The understanding of these causes and their interplay is a prerequisite for the prevention of tumors. Groups participating in the thesis program study both exogenous and endogenous cancer causes using in vitro and in vivo models to identify risk factors and chemo preventive strategies.
? Preclinical development of new therapeutics
Pharmacological investigations of anticancer agents in vivo and in vitro are a main focus of Cancer Research. This has led to a variety of interactions between analytical chemistry, experimental and clinical oncology. Considering experimental tumor pharmacology, the characterization of novel anticancer compounds in a preclinical setting includes the evaluation of cytotoxicity, metabolism, functional studies and interaction with cellular mechanisms of resistance. When a compound successfully passes all preclinical tests and the toxicological safety assessments, the Clinical Departments of Oncology and Hematology offer the opportunity to conduct clinical trials of phase I/II accompanied by pharmacokinetic and pharmacodynamic investigations in humans.