MacInnes group

Ribosome Biogenesis and Disease

We are interested in human diseases that are the result of mutations in elements of the ribosome biogenesis machinery. Ribosome biogenesis is one of the most fundamental functions of a cell, required for the translation of mRNAs into proteins. The mutation or loss of one of the hundreds of proteins involved in the ribosome biogenesis process can result in a myriad of diseases including bone marrow failure, stem cell failure, anemia, and cancer. Using both zebrafish and human patient cells as our model, we use cellular and molecular biology techniques to study the exact mechanisms that result in these diseases when certain ribosome biogenesis genes are mutated. Our ultimate goal is to be able to provide clinicians with proteins and pathways that may be specifically targeted with therapeutic agents in patients carrying ribosome biogenesis mutations in order to prevent the onset of disease.

About the research

Key publications
Pereboom T, van Weele L, Bondt A, MacInnes A.(2011) A zebrafish model of dyskeratosis congenita reveals hematopoetic stem cell formation failure due to ribosomal protein-mediated p53 stabilization. Blood (in press).

Wesseling S, Essers P, Koeners M, Pereboom T, Braam B, Faaseen E, MacInnnes A, Joles, J. (2011) Perinatal exogenous nitric oxide in fawn-hooded hypertensive rats reduces renal ribosome biogenesis in early life. Frontiers in Genetics (in press).

Paridaen J, Janson E, Utami K, Pereboom T, Essers P, van Rooijen C, Zivkovic D, MacInnes A. (2011) The nucleolar GTP-binding proteins Gnl2 and nucleostemin are required for retinal neurogenesis in developing zebrafish. Dev. Biol.15;286-301.

MacInnes A, Amsterdam A., Lees J, Hopkins N. (2011) Cancer: The Outlaw Cell, 3rd edition. American Chemical Society. Chapter on "Zebrafish models of cancer" (in press).

MacInnes A, Amsterdam A., Hopkins N, Lee, J. (2008) Loss of p53 protein synthesis in zebrafish tumors with ribosomal protein gene mutations. Proc. Natl. Acad.Sci. UA 105: 10408-10413.

Wilbanks A, Fralish G, Kirby M, Barak L, Li Y, Caron M. (2004) ß-arrestin2 regulates zebrafish development through the Hedgehog signaling pathway. Science 306: 2264-2267.

Publication list