Christine E. Schaner Tooley PhD
Christine E. Schaner Tooley
PhD
Associate Professor
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Ageing; Cell growth, differentiation and development; DNA Replication, Recombination and Repair; Gene Expression; Molecular and Cellular Biology; Signal Transduction; Stem Cells; Transcription Factors
Professional Summary:
The main goal of my research group is to understand the role of N-terminal methylation in human development and disease. I identified the first eukaryotic N-terminal methyltransferases, NRMT1 and NRMT2, and am now working to identify how these enzymes affect cancer development and ageing. Our laboratory has shown that NRMT1 functions as a tumor suppressor in mammary glands, and its loss sensitizes breast cancer cells to DNA damaging chemotherapeutics. We have also created the first NRMT1 knockout mouse and shown it to have developmental defects, as well as exhibit phenotypes of premature ageing, including neurodegeneration and cognitive impairment. We hypothesize that these premature ageing phenotypes may result from misregulation of different stem cell populations, as we have recently shown that loss of NRMT1 alters both muscle and neural stem cell differentiation. Currently, we are working to understand the exact biochemical pathways that lead from loss of N-terminal methylation to these phenotypes. We are also studying how post-translational modifications on the N-terminus of proteins may interact and dictate protein function, similar to the post-translational modifications found on histone tails.
Education and Training:
- Fellowship, Biochemistry, University of Virginia (2011)
- PhD, Biochemistry, Cell, & Developmental Biology, Emory University (2005)
- BS, Biochemistry, University of Rochester, Magna Cum Laude (2000)
Employment:
- Associate Professor, Biochemistry, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2019-present)
- Assistant Professor, Biochemistry, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2016–2019)
- Assistant Professor, Biochemistry & Molecular Genetics, University of Louisville (2011–2016)
Grants and Sponsored Research:
- January 2022–December 2026
Expanding the Biological Roles of N-terminal methylation
NIGMS
Role: Principal Investigator
$1,978,690 - September 2015–June 2022
Deciphering the Code of N-terminal Post-translational Modification
NIGMS
Role: Principal Investigator
$1,504,140 - April 2018–March 2020
HNRNPA2B1 as a reader of RNA methylation in breast cancer
NCI
Role: Co-Principal Investigator
$356,370 - September 2013–August 2015
The Role of the First Mammalian N-terminal Methyltransferase, NRMT1, in tumorigenesis
NCI
Role: Principal Investigator
$454,074 - September 2011–August 2013
The Role of the First Mammalian N-term. Methyltransferase, NRMT, in tumorigenesis
NCI
Role: Principal Investigator
$176,934 - September 2006–December 2008
Regulation of RCC1 through N-terminal serine methylation
NIGMS
Role: Principal Investigator
Journal Articles:
- Catlin JP, Schaner Tooley CE. (2024) Exploring potential developmental origins of common neurodegenerative disorders. Biochemical Society transactions (Apr).
- Hobble HV, Schaner Tooley CE. (2024) Intrafamily heterooligomerization as an emerging mechanism of methyltransferase regulation. Epigenetics & chromatin (Mar), 17(1): 5. doi:10.1186/s13072-024-00530-0
- Schaner Tooley CE. (2024) Reframing the relationship between motherhood and academic science. Trends in Biochemical Sciences (Jan), 1(49): 1-4. doi:10.1016/j.tibs.2023.08.008
- Parker HV, Schaner Tooley CE. (2023) Opposing regulation of the Na-trimethylase METTL11A by its family members METTL11B and METTL13. The Journal of biological chemistry (Apr), 299(4): 104588. doi:10.1016/j.jbc.2023.104588
- Parker HV, Tooley JG, Schaner Tooley CE. (2023) Optimizing purification and activity assays of N-terminal methyltransferase complexes. Methods in enzymology (Jan), 684: 71-111.
- Tooley JG, Catlin JP, Tooley CES. (2023) METTLing in Stem Cell and Cancer Biology. Stem cell reviews and reports (Jan), 19(1): 76-91.
- Conner MM, Schaner Tooley CE. (2023) Three's a crowd - why did three N-terminal methyltransferases evolve for one job?. Journal of cell science (Jan), 136(2).
- Conner MM, Parker HV, Falcone DR, Chung G, Schaner Tooley CE. (2022) Novel regulation of the transcription factor ZHX2 by N-terminal methylation. Transcription (Sep), 13(1-3): 1-15. doi:10.1080/21541264.2022.2079184
- Catlin JP, Marziali LN, Rein B, Yan Z, Feltri ML, Schaner Tooley CE. (2021) Age-related neurodegeneration and cognitive impairments of NRMT1 knockout mice are preceded by misregulation of RB and abnormal neural stem cell development. Cell death & disease (Oct), 12(11): 1014. doi:10.1038/s41419-021-04316-0
- Tooley JG, Catlin JP, Schaner Tooley CE. (2021) CREB-mediated transcriptional activation of NRMT1 drives muscle differentiation. Transcription (Oct), 12(2-3): 72-88. doi:10.1080/21541264.2021.1963627
- Mackie BD, Chen D, Dong G, Dong C, Parker H, Schaner Tooley CE, Noinaj N, Min J, Huang R. (2020) Selective Peptidomimetic Inhibitors of NTMT1/2: Rational Design, Synthesis, Characterization, and Crystallographic Studies. Journal of medicinal chemistry (Sep), 63(17): 9512-9522. doi:10.1021/acs.jmedchem.0c00689
- Klinge CM, Piell KM, Schaner Tooley CE, Rouchka EC. (2019) HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells. Scientific reports (Jul), 9(1): 9430. doi:10.1038/s41598-019-45636-8
- Nevitt C, Tooley JG, Schaner Tooley CE. (2018) N-terminal acetylation and methylation differentially affect the function of MYL9. Biochem J (Oct), 475(20): 3201-3219.
- Faughn JD, Dean WL, Schaner Tooley CE. (2018) The N-terminal methyltransferase homologs NRMT1 and NRMT2 exhibit novel regulation of activity through heterotrimer formation. Protein Sci (Sep), 27(9): 1585-1599.
- Shields KM, Tooley JG, Petkowski JJ, Wilkey DW, Garbett NC, Merchant ML, Cheng A, Schaner Tooley CE. (2017) Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N-terminal trimethylation. Protein Sci (Aug), 26(8): 1639-1652.
- Cheng A, Gustafson AR, Schaner Tooley CE, Zhang M. (2016) BMP-9 dependent pathways required for the chondrogenic differentiation of pluripotent stem cells. Differentiation (Apr), 92(5): 298-305.
- Fiehn O, Showalter MR, Schaner-Tooley CE. (2016) Registered report: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Elife (Feb), 5 doi:10.7554/eLife.12626
- Yang R, Zhang M, Gustafson AR, Wang E, Cole MP, Schaner Tooley CE, Cheng A. (2015) Loss of Protein Targeting to Glycogen sensitizes human hepatocellular carcinoma cells towards glucose deprivation mediated oxidative stress and cell death. Biosci Rep (May), 35(3): e00207. doi:10.1042/BSR20150090
- Bonsignore LA, Butler JS, Klinge CM, Schaner Tooley CE. (2015) Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis. Oncotarget (May), 6(14): 12248-12263.
- Bonsignore LA, Tooley JG, Van Hoose PM, Wang E, Cheng A, Cole MP, Schaner Tooley CE. (2015) NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging. Mech Ageing Dev (Mar), 146-1: 42-52.
- Tooley JG, Schaner Tooley CE. (2014) New roles for old modifications: emerging roles of N-terminal post-translational modifications in development and disease. Protein Sci (Dec), 23(12): 1641-1649.
- Petkowski JJ, Bonsignore LA, Tooley JG, Wilkey DW, Merchant ML, Macara IG, Schaner Tooley CE. (2013) NRMT2 is an N-terminal monomethylase that primes for its homologue NRMT1. Biochem J (Dec), 456(3): 453-462.
- Petkowski JJ, Schaner Tooley CE, Anderson LC, Shumilin IA, Balsbaugh JL, Shabanowitz J, Hunt DF, Minor W, Macara IG. (2012) Substrate specificity of mammalian N-terminal a-amino methyltransferase NRMT. Biochemistry (Jul), 51(30): 5942-5950.
- Tooley CE, Petkowski JJ, Muratore-Schroeder TL, Balsbaugh JL, Shabanowitz J, Sabat M, Minor W, Hunt DF, Macara IG. (2010) NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Nature (Aug), 466(7310): 1125-1128.
- Chen T, Muratore TL, Schaner-Tooley CE, Shabanowitz J, Hunt DF, Macara IG. (2007) N-terminal alpha-methylation of RCC1 is necessary for stable chromatin association and normal mitosis. Nat Cell Biol (May), 9(5): 596-603.
- Bean CJ, Schaner CE, Kelly WG. (2004) Meiotic pairing and imprinted X chromatin assembly in Caenorhabditis elegans. Nat Genet (Jan), 36(1): 100-105.
- Schaner CE, Deshpande G, Schedl PD, Kelly WG. (2003) A conserved chromatin architecture marks and maintains the restricted germ cell lineage in worms and flies. Developmental cell (Nov), 5(5): 747-57.
- Kelly WG, Schaner CE, Dernburg AF, Lee MH, Kim SK, Villeneuve AM, Reinke V. (2002) X-chromosome silencing in the germline of C. elegans. Development (Cambridge, England) (Jan), 129(2): 479-92.
Books and Book Chapters:
- Schaner CE, Kelly WG. (2006) Germline chromatin. In: WormBook. , 1-14.
Professional Memberships:
- American Society for Cell Biology; Member
- Association of Biochemistry Educators; Member
- International Society of Protein Termini; Member
Presentations:
- "N-terminal methylation and stem cell development" 2022 EMBO Workshop, Protein termini: From mechanisms to biological impact (2022)
- "N-terminal methylation by NRMT1 regulates neural stem cell development and neurodegeneration" 2022 FASEB Summer Research Conference - The Biological Methylation Conference (2022)
- "The role of N-terminal methylation in development and disease" Proteins and Biology Symposium (2022)
- "Panel Discussion I: Tenure Track" Moffitt Cancer Center Junior Scientist Retreat (2021)
Service Activities:
- Department of Microbiology & Immunology Faculty Search Committee (2023–present)
- Luxembourg National Research Fund; Reviewer (2023)
- Search Committee for Senior Associate Dean of Research (2023)
- JSMBS Research Day; Faculty Chair (2023)
- NIH CSF1/CSF2 Study Section; Ad hoc reviewer (2023)
- Faculty Candidate Search Committee (2022–2023)
- Department of Structural Biology Faculty Search Committee (2022–present)
- NIH Special Interest Panel ZRG1-BCMB-J(55)R; Ad hoc reviewer (2022)
- Medical School Admissions; Interviewer (2022–present)
- Paul G. Allen Frontiers Group, Allen Distinguished Investigator Program; Ad hoc reviewer (2022)
- Poster judge for annual CSTEP Summer Research Poster Symposium; Poster Judge (2021–present)
- Served on NIH Special Interest Panel ZRG1 F05 U20 for Feb. and June study sections; Grant reviewer (2021)
- ; Manuscript Reviewer (2021–present)
- UB School of Dental Medicine Executive Council; Committee Member (2020–present)
- Ad Hoc Committee on Promotions to Academic (Tenurial) Ranks; Committee Member (2019–2022)
- Natural Sciences Interdisciplinary Masters Program Admission Committee; Committee Member (2019–present)
- MD/PhD Admissions Committee; Metric Reviewer and Interviewer (2019–present)
- Dept. of Biochemistry representative to the PPBS Steering/Curriculum Committee; Committee Member (2018–present)
- Served as a JSMBS representative to the Faculty Senate; Faculty Senator (2017–2021)