Mammalian Cell Cycle Control Mechanisms
- Immunology, Infection and Cancer
Prof. Dr. Ingrid Hoffmann
Group Leader
The research group Cell Cycle Control and Carcinogenesis is studying the molecular mechanisms underlying centrosome duplication.
Projects
Failure to properly control centrosome number results in supernumerary centrosomes, which are frequently found in cancer cells. Centrosomes are small organelles that contain a pair of barrel-shaped centrioles surrounded by pericentriolar material, PCM. Centrioles duplicate once during the cell cycle to give rise to two mitotic spindle poles, each containing one old and one new centriole. Centrosome duplication must occur in coordination with other cell cycle events, including DNA synthesis.
Most human cancers exhibit centrosome duplication errors which might lead to aneuploidy and cancer formation. How centrioles are assembled and how their numbers are controlled within cells constitute long-standing unresolved questions.
Plk4, a polo-like kinase family member, is the key regulator of centriole duplication. We are studying the pathways underlying Plk4-induced centriole duplication in normal and malignant cells by identifying and characterizing substrates and regulators of Plk4.
To decipher signaling pathways involved in centrosome overduplication in cancer cells we use HPV (human papilloma virus)-induced cervical carcinogenesis as a model system. The high-risk human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Expression of the E7 oncoprotein rapidly drives centrosome duplication errors leading to aberrant centrosome numbers. The goal of our study is to decipher the cellular pathways and mechanisms of action of the high-risk HPV16-E7 oncoprotein leading to centrosomal abnormalities and subsequent genomic instability.
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