Nijman

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About

The Nijman lab is at the Center for Molecular Medicine (CeMM, pronounce \sam\) in Vienna, Austria . We have recently moved into our new research building right next to Vienna General Hospital, one of the largest academic hospitals in Europe. CeMM is an international, independent and interdisciplinary institute of the Austrian Academy of Sciences dedicated to research with a human focus. CeMM’s mission is to combine insight obtained from basic and clinical research and use it to implement the development of innovative therapeutic and diagnostic strategies: “From the clinic to the clinic”

Research scope

In the Nijman lab we are particularly interested in cancer and try to understand the cellular circuitry that is misregulated in this disease with the ultimate aim to identify new patient stratified therapeutic strategies. Cancer cells differ from their normal counterparts by having acquired numerous genetic and epigenetic changes and have re-arranged their cellular network. As a consequence, cancer cells have become dependent on nodes in these networks that are not critical in normal tissues. We perform experiments to identify these cancer vulnerabilities or "Achilles' heels" of cancer cells using large-scale functional genomics and chemical biology. We are currently focusing on breast and lung cancer.

Figure (right). Breast cancer in a mastectomy specimen (top). The cancerous tumour (pale yellow) resembles the figure of a crab, giving the disease its name.

Projects

Synthetic lethal interactions in mammalian cells

A particular type of cancer vulnerability is synthetic lethality/sickness (SSL), a term derived from classical genetics. SSL occurs when two genetic perturbation are only deleterious to a cell or organism in combination. We have recently established a method to screen large numbers of cancer relevant combinations and are now employing this technology in projects relating to breast and lung cancer.

Cell circuits and cancer: Ubiquitin dynamics

Other projects in the lab are generally focussed on cancer-relevant pathways and signaling dynamics, such as ubiquitination/deubiquitination. To identify deubiquitinating enzymes (DUBs) in pathways or processes of interest we employ various post-genomic strategies. We have previously identified DUBs in NF-kappaB signaling, DNA repair and hypoxia signaling. Now, we are also exploring DUBs as potential therapeutic targets in breast cancer.

Figure (right). Ribbon representation of ubiquitin protein, highlighting the secondary structure. α-helices are coloured in blue and the β-sheet in green. The typical attachment point for a further ubiquitin molecule in polyubiquitin chain formation, lysine 48, is shown in pink.