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 research institute of the Austrian Academy of Sciences dedicated to research with a human focus.
“From the clinic to the clinic”
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.
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 therapeutic strategies. Cancer cells differ from their normal counterparts by having acquired numerous genetic and epigenetic changes and have re-arranged their cellular network. Asa 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 "Achilles' heels" of cancer cells using large-scale functional genomics and chemical biology with the ultimate aim to enable patient stratified cancer therapy. 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.
Synthetic lethal interactions in mammalian cells
A particular type of cancer vulnerability is called synthetic lethal/sick (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 with the aim to identify novel therapeutic angles for 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 RNAi libraries directed against all DUBs in the human genome. Using this approach we have previously identifid DUBs in NF-kappaB signaling, DNA repair and hypoxia signaling. Now, we are suing these libraries to identify potential new drug targets for cancer therapy
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.
Collaborations are crucial for modern day science!
Listed here are some friends and collaborators:
Tony Huang (NYU)
Thijn Brummelkamp (MIT, Whitehead Institute)
Rene Bernards (Netherlands Cancer Institute)
Todd Golub (Broad Institute, MIT/Harvard)
Dave Root (Broad Institute, MIT/Harvard)
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