Kristin Baetz

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Kristin Baetz
Interim Assistant Dean, Research Canada Research, Chair in Chemical and Functional Genomics, Professor, Department of Biochemistry, Microbiology and Immunology

Work: (613) 562-5800 ext. 8592
email: kbaetz@uottawa.ca

Dr. Kristin Baetz

Biography

During evolution, there has been a high level of conservation between the budding yeast Saccharomyces cerevisiae's cellular processes and those of mammalian cells. The Baetz laboratory is exploiting powerful systems biology tools and the model organism yeast as a discovery platform for two areas of research: first, identifying novel targets of the enzyme family lysine acetyltransferases that regulate cell cycle progression, chromosome stability, metabolism and stress response, and second, deciphering the biological impact of lipid dysregulation. Given the conservation between yeast and man, our research will be of direct relevance to human cancer biology, metabolic and neurodegenerative diseases.

The Baetz lab accepts students from graduate programs in Biochemistry.

A graph displaying the interactions of the KAT NuA4

NuA4 interactome (Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):E1641-50)

Research Program

The Baetz laboratory exploits the cross-species conservation of biochemical pathway function between yeast and human cells to gain insights into disease mechanism and the mode of action of various compounds. We are developing and applying high throughput yeast chemical and functional genomic screening along with proteomics to two areas of research interest.

The first of these is the study of lysine acetyltransferase (KAT) enzymes. Acetylation of KAT enzymes regulates protein function in a number of ways, including altering the localization, activity, stability and physical interactions of the target protein. Traditionally, lysine acetylation was thought to be largely a nuclear event; however, recent systematic screens have established acetylation as a ubiquitous and 

conserved post-translational modification occurring on thousands of proteins in the cell. We are particularly interested in the S. cerevisiae KAT NuA4: disruption of its KAT activity causes a myriad of phenotypes including defects in chromosome segregation, cytoskeleton rearrangements, metabolism and stress response. We are using both functional genomic and proteomic approaches to identify novel targets of NuA4 and other KATs. As the human equivalent of NuA4 is mis-regulated in a variety of cancers, identifying the proteins that NuA4 regulates allows us to recognize targets for drugs that may one day be used in treating disease.

Second, we are studying chemical genomic approaches to deciphering the biological impact of lipid dysregulation in neurodegenerative diseases, particularly the pathways mediating the cellular effects of a series of alkylacylglycerophosphocholine species that have been associated with Alzheimer ’s disease progression. By harnessing the versatility of Saccharomyces cerevisiae we can quickly unravel mechanistic insights into the cellular pathways mediating the neurotoxic effects of lipids. Our end goal is to identify proteins and pathways that could be targeted to buffer the effects of neurotoxic lipids and slow the progression of Alzheimer’s disease.

Selected Publications

Kennedy MA, Moffat TC, Gable K, Ganesan S, Niewola-Staszkowska K, Johnston A, Nislow C, Giaever G, Harris L, Loewith R, Zaremberg V, Harper ME, Dunn T, Bennett SA, Baetz K.  A Signaling Lipid Associated with Alzheimer's Disease Promotes Mitochondrial Dysfunction. Scientific Reports. 2016 Jan 13;6:19332. doi: 10.1038/srep19332.

Downey M, Baetz K.  Building a KATalogue of acetyllysine targeting and function. Briefings in Functional Genomics, 2015, 1–10 Oct 27

Kennedy MA, Gable K, Niewola-Staszkowska K, Abreu S, Johnston A, Harris LJ, Reggiori F, Loewith R, Dunn T, Bennett SA, Baetz K. A neurotoxic glycerophosphocholine impacts PtdIns-4, 5-bisphosphate and TORC2 signaling by altering ceramide biosynthesis in yeast. PLoS Genetics. 2014 Jan;10(1):e1004010.doi:10.1371/journal.pgen.1004010. Epub 2014 Jan 23.

Mitchell L, Huard S, Cotrut M, Pourhanifeh-Lemeri R, Steunou AL, Hamza A, Lambert JP, Zhou H, Ning Z, Basu A, Côté J, Figeys DA, Baetz K. mChIP-KAT-MS, a method to map protein interactions and acetylation sites for lysine acetyltransferases. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):E1641-50. doi:10.1073/pnas.1218515110. Epub 2013 Apr 9. Erratum in: Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4346.

Usher J, Balderas-Hernandez V, Quon P, Gold ND, Martin VJ, Mahadevan R, Baetz K. Chemical and Synthetic Genetic Array Analysis Identifies Genes that Suppress Xylose Utilization and Fermentation in Saccharomyces cerevisiae. G3. 2011 Sep;1(4):247-58. doi:10.1534/g3.111.000695. Epub 2011 Sep 1.

Hamza A, Baetz K. Iron-responsive transcription factor Aft1 interacts with kinetochore protein Iml3 and promotes pericentromeric cohesin. J Biol Chem. 2012 Feb 3;287(6):4139-47. doi:10.1074/jbc.M111.319319. Epub 2011 Dec 8.

Mitchell L, Lau A, Lambert JP, Zhou H, Fong Y, Couture JF, Figeys D, Baetz K. Regulation of septin dynamics by the Saccharomyces cerevisiae lysine acetyltransferase NuA4. PLoS One. 2011;6(10):e25336. doi:10.1371/journal.pone.0025336. Epub 2011 Oct 3.

Batenchuk C, St-Pierre S, Tepliakova L, Adiga S, Szuto A, Kabbani N, Bell JC, Baetz K, Kærn M. Chromosomal position effects are linked to sir2-mediated variation in transcriptional burst size. Biophys J. 2011 May 18;100(10):L56-8. doi: 10.1016/j.bpj.2011.04.021.

Kennedy MA, Kabbani N, Lambert JP, Swayne LA, Ahmed F, Figeys D, Bennett SA, Bryan J, Baetz K. Srf1 is a novel regulator of phospholipase D activity and is essential to buffer the toxic effects of C16:0 platelet activating factor. PLoS Genet. 2011 Feb 10;7(2):e1001299. doi: 10.1371/journal.pgen.1001299.

Lambert JP, Fillingham J, Siahbazi M, Greenblatt J, Baetz K, Figeys D. Defining the budding yeast chromatin-associated interactome. Mol Syst Biol. 2010 Dec 21;6:448. doi:10.1038/msb.2010.104.

Berthelet S, Usher J, Shulist K, Hamza A, Maltez N, Johnston A, Fong Y, Harris LJ, Baetz K. Functional genomics analysis of the Saccharomyces cerevisiae iron responsive transcription factor Aft1 reveals iron-independent functions. Genetics. 2010 Jul;185(3):1111-28. doi: 10.1534/genetics.110.117531. Epub 2010 May 3.

Lambert JP, Baetz K, Figeys D. Of proteins and DNA--proteomic role in the field of chromatin research. Mol Biosyst. 2010 Jan;6(1):30-7. doi:10.1039/b907925b. Epub 2009 Sep 3. Review.

Lambert JP, Mitchell L, Rudner A, Baetz K, Figeys D. A novel proteomics approach for the discovery of chromatin-associated protein networks. Mol Cell Proteomics. 2009 Apr;8(4):870-82. doi:10.1074/mcp.M800447-MCP200. Epub 2008 Dec 22.

Mitchell L, Lambert JP, Gerdes M, Al-Madhoun AS, Skerjanc IS, Figeys D, Baetz K. Functional dissection of the NuA4 histone acetyltransferase reveals its role as a genetic hub and that Eaf1 is essential for complex integrity. Mol Cell Biol. 2008 Apr;28(7):2244-56. doi:10.1128/MCB.01653-07. Epub 2008 Jan 22.

Martin DG, Baetz K, Shi X, Walter KL, MacDonald VE, Wlodarski MJ, Gozani O, Hieter P, Howe L. The Yng1p plant homeodomain finger is a methyl-histone binding module that recognizes lysine 4-methylated histone H3. Mol Cell Biol. 2006 Nov;26(21):7871-9. Epub 2006 Aug 21.

Baetz K, Kaern M. Predictable trends in protein noise. Nat Genet. 2006 Jun;38(6):610-1.

Baetz K, Measday V, Andrews B. Revealing hidden relationships among yeast genes involved in chromosome segregation using systematic synthetic lethal and synthetic dosage lethal screens. Cell Cycle. 2006 Mar;5(6):592-5. Epub 2006 Mar 15. Review.

Martin DG, Grimes DE, Baetz K, Howe L. Methylation of histone H3 mediates the association of the NuA3 histone acetyltransferase with chromatin. Mol Cell Biol. 2006 Apr;26(8):3018-28.

Keogh MC, Mennella TA, Sawa C, Berthelet S, Krogan NJ, Wolek A, Podolny V, Carpenter LR, Greenblatt JF, Baetz K, Buratowski S. The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4. Genes Dev. 2006 Mar 15;20(6):660-5.

Measday V, Baetz K, Guzzo J, Yuen K, Kwok T, Sheikh B, Ding H, Ueta R, Hoac T, Cheng B, Pot I, Tong A, Yamaguchi-Iwai Y, Boone C, Hieter P, Andrews B. Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13956-61. Epub 2005 Sep 19.

Krogan NJ, Baetz K, Keogh MC, Datta N, Sawa C, Kwok TC, Thompson NJ, Davey MG, Pootoolal J, Hughes TR, Emili A, Buratowski S, Hieter P, Greenblatt JF. Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4. Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13513-8. Epub 2004 Sep 7. Erratum in: Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6410.

Baetz K, McHardy L, Gable K, Tarling T, Rebérioux D, Bryan J, Andersen RJ, Dunn T, Hieter P, Roberge M. Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4525-30. Epub 2004 Mar 15.

Baetz KK, Krogan NJ, Emili A, Greenblatt J, Hieter P. The ctf13-30/CTF13 genomic haploinsufficiency modifier screen identifies the yeast chromatin remodeling complex RSC, which is required for the establishment of sister chromatid cohesion. Mol Cell Biol. 2004 Feb;24(3):1232-44.

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