Christine Schaner Tooley, Ph.D
Office: (502) 852-0322
Lab: (502) 852-7488
Fax: (502) 852-2660
Address: 580 S. Preston St., Delia Baxter Building (Baxter II), Rm 102A, Louisville, KY 40202
B.S. – Biochemistry, University of Rochester, 2000.
Ph. D. – Biochemistry, Cell and Developmental Biology, Emory University (Dr. William Kelly), 2005
Postdoctoral Fellowship – Department of Microbiology, University of Virginia (Dr. Ian Macara), 2005-2011
- Renate Meier, Danial Malik
- the function of N-terminal protein methylation in development and tumorigenesis
While great progress has been made in researching the genes involved in the onset and progression of cancer, the advent of microarray analysis has shown there are still many important genes that remain unstudied. To achieve a complete understanding of tumorigenesis and obtain an inclusive list of potential druggable targets, we need to identify the functions of the unstudied genes. One such protein, Mettl11a, is under-expressed in breast cancer, glioblastoma, and leukemia, but until recently, little has been known about its function. I identified Mettl11a as the first mammalian N-terminal methyltransferase and have renamed it NRMT (N-terminal RCC1 methyltransferase). NRMT is a highly conserved, ubiquitously expressed nuclear methyltransferase that can mono-, di-, or trimethylate the N-termini of proteins containing its consensus sequence. I originally purified NRMT as the N-terminal methyltransferase for the Ran-GEF RCC1, but have also verified the tumor suppressor retinoblastoma protein (RB), the oncoprotein SET, and a variety of other proteins as substrates. In support of the microarray data, initial functional studies have shown loss of NRMT disrupts RCC1 binding to DNA and causes growth and mitotic defects often considered to contribute to cancer progression. The work in my lab is aimed at understanding the role of N-terminal methylation on protein and cellular function, and discovering how misregulation of NRMT, and consequently N-terminal methylation, can lead to cancer progression.
Schaner Tooley, C. E., Petkowski, J., Muratore-Schroeder, T., Balsbaugh, J., Shabanowitz, J., Sabat, M., Minor, W., Hunt, D., and Macara, I.G. (2010). NRMT is an -N-methyltransferase that methylates RCC1 and Retinoblastoma Protein. Nature 466 (7310), 1125-1128.
(Commentaries in Cell, Nature Reviews Molecular Cell Biology, and Faculty of 1000 Biology)
Chen, T., Muratore, T. L., Schaner-Tooley, C. E., Shabanowitz, J., Hunt, D. F., and Macara, I. G. (2007). N-terminal alpha-methylation of RCC1 is necessary for stable chromatin association and normal mitosis. Nature Cell Biology 9 (5), 596-603.
Schaner, C. E. and Kelly, W. G., Germline chromatin (January 24, 2006), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.73.1, http://www.wormbook.org.
Bean, C.J.*, Schaner, C.E.*, and Kelly, W.G. (2004). Meiotic Pairing and Imprinted X Chromatin Assembly in C. elegans. Nature Genetics 36 (1), 100-105. * Authors contributed equally to this work
Schaner, C.E., Deshpande, G., Schedl, P.D., and Kelly, W. G. (2003). A Conserved Chromatin Architecture Marks and Maintains the Restricted Germ Cell Lineage in Worms and Flies. Developmental Cell 5 (5), 747-757.
Kelly, W.G., Schaner, C.E., Dernburg, A.F., Lee, M.H., Kim, S.K., Villeneuve, A.M., and Reinke, V. (2002). X-chromosome silencing in the germline of C. elegans. Development 129, 479-492.