Tony R. Hazbun, Ph.D. Assistant Professor of Medicinal Chemistry and Molecular Pharmacology Phone: (765) 496-8228 Fax: (765) 494-1414 E-mail: thazbun@purdue.edu Full directory listing

Specialization: Functional Genomics and Systems Biology, Chemical Genetics

Education

Research: Functional Genomics and Systems Biology, Chemical Genetics

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.

Interests

• Mitosis and Cancer
• Chromosome segregation
• Aurora kinases
• Hsp90

Teaching

• MCMP 422 - Immunology
• PHRM 401 - Integrated Lab III
• MCMP 514 - Advanced Medicinal Analysis
• MCMP 690G - Molecular Targets: Cancer

Grants

"Integrated Genomewide Analysis of the Ipl1 Kinase Signaling Network", 7/01/2009-6/30/2013, R01 funded by NIH, NIGMS

"High-throughput Chemotyping of Yeast Signature Strains Reflecting Hsp90 Biology", 09/30/2007 - 05/31/2010, R21 MLPCN funded by NIH, NINDS; 1R21NS061667-01 (co-investigator: V Jo Davisson, Purdue University)

PhRMA Foundation: Uncovering the Proteomic Network Surrounding the Yeast Aurora Kinase, Ipl

Showalter Trust: DJ-1: an "ON" for Cell Survival Pathways in the Brain, (co-investigator: J-C Rochet, Purdue University)

Showalter Trust: Identification of Novel Anti-cancer Drug Targets in Cells Overexpressing Lyar, (co-investigator: S Mendrysa, Purdue University)

Showalter Trust: Cell Cycle Regulatory Functions of the 14-3-3 Protein Family, (co-investigators: Mark Hall and Harry Charbonneau, Purdue University)

Representative Publications

1. Luo J, Xu X, Hall H, Hyland EM, Boeke JD, Hazbun TR, Kuo M-H. Histone H3 Exerts Key Function in Mitotic Checkpoint Control. Mol Cell Biol 30:537-49, 2010

2. Wong J, Nakajima Y, Westermann S, Shang C, Goodner C, Houshmand P, Chan C, Fields S, Drubin DG, Barnes G, Hazbun T. A protein interaction map of the mitotic spindle. Mol Biol Cell 18:3800-9, 2007

3. Jin F, Avramova L, Huang J, Hazbun T. A yeast two-hybrid smart-pool-array system for protein-interaction mapping. Nat Methods 4(5):405-7, 2007

4. Montpetit B, Hazbun TR, Fields S, Hieter P. Sumoylation of the budding yeast kinetochore protein Ndc10 is required for Ndc10 spindle localization and proper anaphase spindle elongation. J Cell Biol 174(5):653-63, 2006

5. Jin F, Hazbun T, Michaud GA, Salcius M, Predki PF, Fields S, Huang J. A pooling-deconvolution strategy for biological network elucidation. Nat Methods 3(3):183-9, 2006

6. Gingras AC, Caballero M, Zarske M, Sanchez A, Hazbun TR, Fields S, Sonenberg N, Hafen E, Raught B, Aebersold R. A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity. Mol Cell Proteomics 4(11): 1725-40, 2005

7. Guo D*, Hazbun TR*, Xu X-J, Fields S, Kuo M-H. A Tethered Catalysis Two-Hybrid System to Identify Protein-Protein Interactions Requiring Post-Translational Modifications. Nature Biotech Jul;22(7):888-92, 2004* Equal contributions

8. Hazbun TR, Malmstrom L, Anderson S, Graczyk BJ, Fox B, Riffle M, Sundin BA, Aranda J.D, McDonald WH, Chiu C-H, Snydsman BE, Bradley P, Muller EGD, Fields S, Baker D, Yates III, JR, Davis TN. Assigning Function to Yeast Proteins by Integration of Technologies. Mol Cell 12 (6):1353-65, 2003

9. Shang C, Hazbun TR, Cheeseman IM, Aranda J, Fields S, Drubin DG, Barnes G. Kinetochore Protein Interactions and their Regulation by the Aurora Kinase Ipl1. Mol Biol Cell 14(8):3342-55, 2003

10. Hazbun TR, Fields S. A genome-wide screen for site-specific DNA-binding proteins. Mol Cell Proteomics 1(7):538-43, 2002