Tony R. Hazbun
Ph.D. 1997 - University of Notre Dame
Postdoc. 1998-2005 - University of Washington (Stanley Fields)
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Chromosomal instability due to aberrant chromosome segregation is a hallmark of cancer, suggesting that a more detailed and mechanistic understanding of the molecular processes that control the faithful segregation of chromosomes will lead to new therapeutic strategies to control cancer. An example of this promise is evident in the Aurora kinases, which are important regulators of chromosome segregation. Several specific Aurora kinase inhibitors have demonstrated anti-proliferative activities and are proceeding to clinical trials even though we do not understand the multiple roles of this kinase. Our research involves the development of functional genomics approaches in baker's yeast, Saccharomyces cerevisiae, to focus on the kinase-signaling network of the yeast Aurora kinase, Ipl1. The downstream effects these phosphorylated substrates have on protein-protein interactions will be determined using an integrated approach relying on a phosphomutant scanning approach in conjunction with two-hybrid technology and systematic genetic studies. Identification of phosphomodulated genetic interactions and phosphomodulated protein-protein interactions related to Ipl1 and it's control of mitosis and chromosome segregation in yeast, should serve as a guide toward the analysis of and ultimately, intervention in, the abnormal mitotic pathways that propagate cancer cells.
- Mitosis and Cancer
- Chromosome segregation
- Aurora kinases
- Chaperone biology
- MCMP 422 - Immunology
- PHRM 821 Professional Program Laboratory II
- MCMP 514 - Advanced Medicinal Analysis
- MCMP 690G - Molecular Targets: Cancer
Honors and Credentials
Positions and Employment
1998-2005 Howard Hughes Medical Institute, Postdoctoral Associate, University of Washington
2001-2005 Two-hybrid Screening Coordinator, Yeast Resource Center (NCRR), University of Washington
2005-2011 Assistant Professor of Medicinal Chemistry and Molecular Pharmacology, Purdue University
2005-present Full Member of the Bindley Bioscience Center, Discovery Park, Purdue University
2011-present Associate Professor of Medicinal Chemistry and Molecular Pharmacology, Purdue University
Other Experience and Professional Memberships
1994-1997 Teaching Assistant, Department of Biology, University of Notre Dame
2003 Future Faculty Fellows program, HHMI sponsored workshop
2005-present Instructor – Immunology for Pharm.D. students
2005-present Instructor – Cell Cycle and Drug Discovery for Graduate Students
Professional memberships Genetics Society of America, ABMB
Ad hoc reviewing activities
Reviewed for Nature Biotechnology, Biochemistry, PNAS, PLoS Genetics, PLoS Pathogens, PLoS One, Protein Science, Genome Biology, Cold Spring Harbor Laboratories Protocol, Biotechniques, Bioinformatics, Assay Development and Technologies, Genes Genomes and Genetics (G3), Methods, Wiley Encyclopedia of Chemical Biology.
Reviewed grants for:
National Institute of Health (NIH) – Genomics, Computational Biology and Technology Study Section
National Science Foundation (NSF)
Biomedical Research Council A*STAR – Singapore
Civilian Research and Development Foundation (CRDF)
New Zealand Ministry of Science and Innovation (MSI)
Administration and Committee Work
PULSe Molecular Signaling and Cancer Biology Training Group Chair
MCMP Graduate Admissions Committee Chair
1: Thangamani S, Eldesouky HE, Mohammad H, Pascuzzi PE, Avramova L, Hazbun TR, Seleem MN. Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells. Biochim Biophys Acta. 2016 Oct 3;1861(1 Pt A):3002-3010. doi: 10.1016/j.bbagen.2016.09.029. [Epub ahead of print] PubMed PMID: 27712973.
2: Aslam K, Tsai CJ, Hazbun TR. The small heat shock protein Hsp31 cooperates with Hsp104 to modulate Sup35 prion aggregation. Prion. 2016 Oct 3:0. [Epub ahead of print] PubMed PMID: 27690738.
3: Wang S, Gribskov M, Hazbun TR, Pascuzzi PE. CellMiner Companion: an interactive web application to explore CellMiner NCI-60 data. Bioinformatics. 2016 Aug 1;32(15):2399-401. doi: 10.1093/bioinformatics/btw162. PubMed PMID: 27153600.
4: Aslam K, Hazbun TR. Hsp31, a member of the DJ-1 superfamily, is a multitasking stress responder with chaperone activity. Prion. 2016 Mar 3;10(2):103-11. doi: 10.1080/19336896.2016.1141858. PubMed PMID: 27097320; PubMed Central PMCID: PMC4981205.
5: Tsai CJ, Aslam K, Drendel HM, Asiago JM, Goode KM, Paul LN, Rochet JC, Hazbun TR. Hsp31 Is a Stress Response Chaperone That Intervenes in the Protein Misfolding Process. J Biol Chem. 2015 Oct 9;290(41):24816-34. doi: 10.1074/jbc.M115.678367. PubMed PMID: 26306045; PubMed Central PMCID: PMC4598993.
6: Thapa KS, Oldani A, Pagliuca C, De Wulf P, Hazbun TR. The Mps1 kinase modulates the recruitment and activity of Cnn1(CENP-T) at Saccharomyces cerevisiae kinetochores. Genetics. 2015 May;200(1):79-90. doi: 10.1534/genetics.115.175786. PubMed PMID: 25716979; PubMed Central PMCID: PMC4423383.
7: Mukherjee D, Sen A, Boettner DR, Fairn GD, Schlam D, Bonilla Valentin FJ, Michael McCaffery J, Hazbun T, Staiger CJ, Grinstein S, Lemmon SK, Claudio Aguilar R. Bem3, a Cdc42 GTPase-activating protein, traffics to an intracellular compartment and recruits the secretory Rab GTPase Sec4 to endomembranes. J Cell Sci. 2013 Oct 15;126(Pt 20):4560-71. doi: 10.1242/jcs.117663. PubMed PMID: 23943876; PubMed Central PMCID: PMC3795334.
8: Song B, Liu XS, Rice SJ, Kuang S, Elzey BD, Konieczny SF, Ratliff TL, Hazbun T, Chiorean EG, Liu X. Plk1 phosphorylation of orc2 and hbo1 contributes to gemcitabine resistance in pancreatic cancer. Mol Cancer Ther. 2013 Jan;12(1):58-68. doi: 10.1158/1535-7163.MCT-12-0632. PubMed PMID: 23188630; PubMed Central PMCID: PMC3732037.
9: Bock LJ, Pagliuca C, Kobayashi N, Grove RA, Oku Y, Shrestha K, Alfieri C, Golfieri C, Oldani A, Dal Maschio M, Bermejo R, Hazbun TR, Tanaka TU, De Wulf P. Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore. Nat Cell Biol. 2012 May 6;14(6):614-24. doi: 10.1038/ncb2495. Erratum in: Nat Cell Biol. 2013 Mar;15(3):335. PubMed PMID: 22561345; PubMed Central PMCID: PMC3438452.
10: Ren L, McLean JR, Hazbun TR, Fields S, Vander Kooi C, Ohi MD, Gould KL. Systematic two-hybrid and comparative proteomic analyses reveal novel yeast pre-mRNA splicing factors connected to Prp19. PLoS One. 2011 Feb 28;6(2):e16719. doi: 10.1371/journal.pone.0016719. Erratum in: PLoS One. 2011;6(9). doi: 10.1371/annotation/62e74a1c-c922-495b-9aaf-eebfe6b85ff5. PubMed PMID: 21386897; PubMed Central PMCID: PMC3046128.
11: Luo J, Xu X, Hall H, Hyland EM, Boeke JD, Hazbun T, Kuo MH. Histone h3 exerts a key function in mitotic checkpoint control. Mol Cell Biol. 2010 Jan;30(2):537-49. doi: 10.1128/MCB.00980-09. PubMed PMID: 19917722; PubMed Central PMCID: PMC2798460.
12: Wong J, Nakajima Y, Westermann S, Shang C, Kang JS, Goodner C, Houshmand P, Fields S, Chan CS, Drubin D, Barnes G, Hazbun T. A protein interaction map of the mitotic spindle. Mol Biol Cell. 2007 Oct;18(10):3800-9. PubMed PMID: 17634282; PubMed Central PMCID: PMC1995735.