Dr. Nisar Malek
Institute for Molecular Biology and Dept. of Gastroenterology
Our lab is studying basic mechansims of cell division. We are particularly intersted in the control of proteins involved in the regulation of the eukaryotic cell cycle. Two classes of proteins can be distinguished, activators of cell divison i.e. cyclin-kinase complexes and inhibitors of proliferation so called cyclin kinase inhibitors (cki). We are currently focusing on the regulation of the cyclin kinase inhibitor p27. As the levels of p27 within an eukaryotic cell determines whether the cell can divide or must stay in a quiescent state, the regulation of this cki is of fundamental importance under normal and pathological conditions of cell proliferation
We have previously generated several mouse models which allow us to investigate the role of p27 protein turnover in tumorigenesis. This is especially important for the understanding of human tumorigenesis as the p27 protein is rapidly degraded in human tumors. The characterisation of tumor initiation, progression and metastasis formation in these in vivo models as well as in primary cell lines is the prerequisite for the development of new drugs that aim at the stabilisation of tumor suppressor proteins in cancer cells. A process in which the lab is actively involved.
Dr. N. Malek, MD Dr. H. Sundberg, PhD Dr. J. Vervoorts, PhD Inke Timmerbeul, cand.med.
Tissue culture, protein purification, immunoprecipitations and western Blotting, production of Retroviral and Adenoviral Vectors, tissue processing and staining techniques, all techniques of DNA modification.
N.P. Malek, H. Sundberg, S. McGrew, K. Nakayama, T.R. Kyriakides, J. Roberts A mouse knock-in model exposes two sequential proteolytic pathways that regulate p27kip1 in G1 and S phase. Nature, 413, 323-27, (2001)