Laura Trinkle-Mulcahy


Laura Trinkle-Mulcahy
Assistant Professor, Department of Cellular and Molecular Medicine

Work: (613) 562-5800 ext. 8068

Picture of Dr. Laura Trinkle-Mulcahy


Trinkle Lab


Human cells express thousands of proteins, many of which are regulated by the addition or removal of a negatively charged phosphate group. The enzymes responsible for this regulation are the protein kinases (which add phosphates) and protein phosphatases (which remove phosphates). The balance of the activities of these enzymes determines the "phospho-state" of each protein, which can in turn affect structure, location within the cell, interaction with other proteins and/or enzymatic activity. Aberrant phosphorylation has been linked to many diseases, including diabetes and cancer, and we study the targeting of phosphatase complexes within living cells to identify and understand that connection.

The Trinkle-Mulcahy lab accepts students from graduate programs in Cellular and Molecular Medicine and Biochemistry.

A three-dimensional computer rendering of a human nucleus

3D rendering of a high-resolution fluorescence image of a human cell nucleus, showing the nuclear envelope (orange; detected with antibodies that recognize the nuclear pore complex), chromatin (blue; DNA stained with Hoechst 33342 dye) and nucleoli (green; detected with antibodies that recognize the nucleolar protein B23/NPM1).

Research Program

Reversible protein phosphorylation is the major general mechanism regulating most physiological processes in eukaryotic cells. Protein kinases and protein phosphatases play key roles in the control of cell proliferation, differentiation and a host of other critical events. A common theme in phosphatase regulation is a mechanism whereby localization of the enzyme determines its access to substrates. In the case of the protein phosphatase 1 (PP1), this is mediated by the interaction of the catalytic subunit with a panel of regulatory proteins termed “targeting subunits” to generate a range of holoenzyme complexes with distinct subcellular roles. The evolution of this unique combinatorial regulatory mechanism provides the opportunity to develop highly specific PP1 inhibitors, based on targeted disruption of single complexes.

Although biochemical, bioinformatic, and proteomic approaches have identified a wide range of targeting subunits, the current list still cannot account for the large number of regulatory pathways in which PP1 is known to play a critical role. The continuing identification and characterization of new targeting subunits is thus critical to our understanding of targeted phosphatase activity. Using a unique and powerful combination of live cell imaging with cell fractionation and quantitative interactome profiling, we have provided the first comprehensive map of functional PP1 complexes throughout the cell, demonstrating its essential roles in diverse processes including ribosome biogenesis, DNA damage repair and chromosome segregation. Our main focus now is on understanding the means by which levels and targeting of PP1 catalytic subunits are dynamically regulated to maintain cellular homeostasis and how errors in this process can lead to cellular dysfunction and disease development.

Selected Publications

Prévost M, Chamousset D, Nasa I, Freele E, Morrice N, Moorhead G, Trinkle-Mulcahy L. Quantitative fragmentome mapping reveals novel, domain-specific partners for the modular protein RepoMan (recruits PP1 onto mitotic chromatin at anaphase). Mol Cell Proteomics. 2013 May;12(5):1468-86. doi:10.1074/mcp.M112.023291. Epub 2013 Jan 29.

Trinkle-Mulcahy L. Resolving protein interactions and complexes by affinity purification followed by label-based quantitative mass spectrometry. Proteomics. 2012 May;12(10):1623-38. doi: 10.1002/pmic.201100438. Review.

Chamousset D, De Wever V, Moorhead GB, Chen Y, Boisvert FM, Lamond AI, Trinkle-Mulcahy L. RRP1B targets PP1 to mammalian cell nucleoli and is associated with Pre-60S ribosomal subunits. Mol Biol Cell. 2010 Dec;21(23):4212-26. doi:10.1091/mbc.E10-04-0287. Epub 2010 Oct 6.

Chamousset D, Mamane S, Boisvert FM, Trinkle-Mulcahy L. Efficient extraction of nucleolar proteins for interactome analyses. Proteomics. 2010 Aug;10(16):3045-50. doi: 10.1002/pmic.201000162.

Trinkle-Mulcahy L, Boulon S, Lam YW, Urcia R, Boisvert FM, Vandermoere F, Morrice NA, Swift S, Rothbauer U, Leonhardt H, Lamond A. Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes. J Cell Biol. 2008 Oct 20;183(2):223-39. doi: 10.1083/jcb.200805092.

Trinkle-Mulcahy L, Lamond AI. Toward a high-resolution view of nuclear dynamics. Science. 2007 Nov 30;318(5855):1402-7. Review.

Moorhead GB, Trinkle-Mulcahy L, Ulke-Lemée A. Emerging roles of nuclear protein phosphatases. Nat Rev Mol Cell Biol. 2007 Mar;8(3):234-44. Review.

Trinkle-Mulcahy L, Andersen J, Lam YW, Moorhead G, Mann M, Lamond AI. Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability. J Cell Biol. 2006 Feb 27;172(5):679-92. Epub 2006 Feb 21.

Trinkle-Mulcahy L, Andrews PD, Wickramasinghe S, Sleeman J, Prescott A, Lam YW, Lyon C, Swedlow JR, Lamond AI. Time-lapse imaging reveals dynamic relocalization of PP1gamma throughout the mammalian cell cycle. Mol Biol Cell. 2003 Jan;14(1):107-17.

Trinkle-Mulcahy L, Sleeman JE, Lamond AI. Dynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells. J Cell Sci. 2001 Dec;114(Pt 23):4219-28.

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