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
Essers P, Klasson T, Pereboom T, Mans D, Nicastro M, Boldt K, Giles R, Macinnes A. The von Hippel-Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2. Oncogene. 2014 Jan 27. doi: 10.1038/onc.2013.598.
Pereboom T, Bondt A, Pallaki P, Klasson T, Goos J, Essers P, Koerkamp M, Gazda H, Holstege F, MacInnes A. Translation of branched-chain aminotransferase-1 transcripts is impaired in cells haploinsufficient for ribosomal protein genes. Exp. Hematol. 2014 Jan 23. pii: S0301-472X(14)00053-8.
van Heesch S, van Iterson M, Jacobi J, Boymans S, Essers P, de Bruijn E, Hao W, MacInnes A, Cuppen E, Simonis M. Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes. Genome Biology. 2014 Jan 7;15(1):R6.
Essers P, Pereboom T, Goos Y, Paridaen J, MacInnes A. A comparative study of nucleostemin family members in zebrafish reveals specific roles in ribosome biogenesis. Dev. Biol. 2014 Jan 15;385(2):304-15.
Stout G, Stigter E, Essers P, Mulder K, Kolkman A, Snijders D, van den Broek N, Betist M, Korswagen H, MacInnes A, Brenkman A Insulin/IGF-1-mediated longevity is marked by reduced protein metabolism. Mol Syst Biol. 2013 Jul 2;9:679.
Pereboom T, van Weele L, Bondt A, MacInnes A. A zebrafish model of dyskeratosis congenita reveals hematopoetic stem cell formation failure due to ribosomal protein-mediated p53 stabilization. Blood. 2011 Nov 17;118(20):5458-65.
Wesseling S, Essers P, Koeners M, Pereboom T, Braam B, Faaseen E, MacInnnes A, Joles, J. Perinatal exogenous nitric oxide in fawn-hooded hypertensive rats reduces renal ribosome biogenesis in early life. Frontiers in Genetics. 2011 Aug 29;2:52.
Paridaen J, Janson E, Utami K, Pereboom T, Essers P, van Rooijen C, Zivkovic D, MacInnes A. The nucleolar GTP-binding proteins Gnl2 and nucleostemin are required for retinal neurogenesis in developing zebrafish. Dev. Biol. 2011 15;286-301.
MacInnes A, Amsterdam A., Lees J, Hopkins N. Cancer: The Outlaw Cell, 3rd edition. Chapter on "Zebrafish models of cancer". American Chemical Society, ISBN-10: 0841200009.
MacInnes A, Amsterdam A., Hopkins N, Lee, J. Loss of p53 protein synthesis in zebrafish tumors with ribosomal protein gene mutations. Proc. Natl. Acad.Sci. 2008 UA 105: 10408-10413.
Wilbanks A, Fralish G, Kirby M, Barak L, Li Y, Caron M. ß-arrestin2 regulates zebrafish development through the Hedgehog signaling pathway. Science. 2004 306: 2264-2267.