Robert Hanzlik Research
Not accepting any students/postdoctoral fellows at the present time.
- B.A., Chemistry and Biology, 1966, Southern Illinois University at Carbondale
- Ph.D., Organic Chemistry, 1970, Stanford University (E. E. van Tamelen)
- NSF/NATO Postdoctoral Fellow, Cambridge University, 1970-71 (Jack Lewis)
- NSF Fellow and Teaching Assistant, Stanford University, 1966-70
- NSF/NATO Postdoctoral Fellow, Cambridge University 1970-71
- Assistant Professor (1971-76), Associate Professor (1976-80), Professor (1980-present), Department of Medicinal Chemistry, University of Kansas
- Frederick J. Di Carlo Distinguished Service Award, International Society for the Study of Xenobiotics, 2013
- Taito O. Soine Award in Medicinal Chemistry, University of Minnesota, 2012
- Leading Light Award, University of Kansas, 2012
- 40 Year Service Award, State of Kansas, 2012
- Awarded Honorary Life Membership by the International Society for the Study of Xenobiotics, 2001
- Excellence in Teaching Award, KU Center for Teaching Excellence, 1999
- Nelson Voldeng Memorial Lecturer, MALTO Medicinal Chemistry and Pharmacognosy Meeting, 1995
- Elected a Fellow of the American Association for Advancement of Science, 1994
- Invited Guest Lecturer, Eightieth Anniversary Celebration, Zhejiang Medical University, China, 1992
- Sato Memorial International Award, from the Foundation for Advanced Education in Science and the Pharmaceutical Society of Japan, 1991
- The Olin Petefish Research Award in the Basic Sciences, University of Kansas, 1989
- U. S. Honorary Ramsey Memorial Fellow, University of Cambridge, England, 1970-71
- NSF Fellow, Stanford University, 1966-70
- Graduated with Honors, Southern Illinois University, 1966. Outstanding senior chemistry major award, 1966. Outstanding senior zoology major award, 1965.
- Elected to membership in Phi Eta Sigma (1962), Phi Kappa Phi (1965), Rho Chi (1972), Sigma Xi (1972).
Completed Research Projects (no longer active)
Chemical mechanisms of cytotoxicity.
Relatively simple organic molecules are sometimes capable of causing considerable toxicity to cells and tissues in vivo. Examples include solvents such as chloroform, bromobenzene and p-xylene, organosulfur compounds such as thioacetamide, thiobenzamide and the herbicide molinate, the analgesic drug acetaminophen, the common antioxidant BHT, and many others. The cytotoxicity of this diverse group of compounds stems from their common tendency to undergo biotransformation to chemically reactive metabolites which then covalently modify cellular proteins leading to cytotoxicity and even cell death. A major interest of our laboratory lies in the elucidation of the steps in this pathway, including identification of the reactive metabolites, the proteins they modify, the adduct structures formed, and their biochemical consequences for protein-protein interaction and signaling. Carefully designed "probe" molecules are synthesized, often with stable- or radio-isotope labeling, and their metabolism is investigated using state-of-the-art analytical methods. Adducted proteins are located on 2D gels by autoradiography and identified, along with their adducts, by modern methods of proteomic analysis based on HPLC/MS/MS.
Visit Chemical mechanisms of cytotoxicity for more information.
COBRE Center in Protein Structure and Function.
In addition to the research activities listed above, Dr. Hanzlik is the Principal Investigator and Director of a NIH Center of Biomedical Research Excellence in Protein Structure and Function. The center provides research support and mentoring to junior and senior faculty on four campuses in Kansas. The Center also hosts three service laboratories that are accessed by more than 75 different research groups across the country.
Visit COBRE Center in Protein Structure and Function for more information.
Keisuke Ikehata, Tatyana G. Duzhak, Nadezhda A. Galeva, Tao Ji, Yakov M. Koen and Robert P. Hanzlik, "Protein Targets of Reactive Metabolites of Thiobenzamide in Rat Liver In Vivo." Chem. Res. Toxicol., 2008, 21, 1432–1442. PMID: 18547066
Kristin Bowman-James, Gary L. Grunewald and Robert P. Hanzlik, "Eulogy to Mathias P. Mertes, 1932-1989." Med. Res. Rev. 29(1),1-2 (2009).
Robert P. Hanzlik, Jianwen Fang, Yakov M. Koen, "Filling and Mining the Reactive Metabolite Target Protein Database," Chem.-Biol. Interactions, 179, 38-44 (2009). PMID: 18823962 PMC2669808
M. A. Altaweel, J. Ver Hoeve, J. Eells, R. P. Hanzlik and B. Zhang, "Ocular and Systemic Safety Evaluation of Calcium Formate." J. Ocular Pharmacol. Toxicol. 25, 223-230 (2009). PMID: 19456257
Jianwen Fang, Yakov Koen and Robert P. Hanzlik, "Bioinformatic analysis of xenobiotic reactive metabolite target proteins and their interacting partners." BMC Chemical Biology 2009, 9:5 (12 June 2009). PMID: 19523227
Douglas S. Auld, Scott Lovell, Natasha Thorne, Wendy A. Lea, David J. Maloney, Min Shen, Ganesha Rai, Kevin Battaile, Craig J. Thomas, Anton Simeonov, Robert P. Hanzlik, and James Inglese, "Molecular Basis for the High Affinity Binding and Stabilization of Firefly Luciferase by PTC124." Proc. Nat. Acad. Sci. USA 2010, 107, 4878-83. PMID 20194791
Diganta Sarma and Robert P. Hanzlik, "Synthesis of carbon-14, carbon-13 and deuterium labeled thioacetamide and thioacetamide S-oxide" Journal of Labelled Compounds and Radiopharmaceuticals, 54, 795-798 (2011). PMID: 22667464
Yakov M. Koen, Diganta Sarma,aTodd D. Williams, Nadezhda A. Galeva, R. Scott Obach and Robert P. Hanzlik, "Identification of Protein Targets of Reactive Metabolites of Tienilic Acid in Human Hepatocytes." Chem. Res. Toxicol. 25, 1145-54 (2012). PMID: 22462724 http://dx.doi.org/10.1021/tx3001658
Yakov M. Koen, Heather Hajovsky, Ke Liu, Todd D. Williams, Nadezhda A. Galeva# Jeffrey L. Staudinger and Robert P. Hanzlik, "Liver Protein Targets of Hepatotoxic 4-Bromophenol Metabolites." Chem. Res. Toxicol. 25, 1777-1786 (2012). http://dx.doi.org/10.1021/tx3002675 PMC3431021
Diganta Sarma, Heather Hajovsky, Yakov M. Koen, Nadezhda A. Galeva, Todd D. Williams, Jeffrey L. Staudinger, and Robert P. Hanzlik, "Covalent Modification of Lipids and Proteins in Rat Hepatocytes and in Vitro by Thioacetamide Metabolites." Chem. Res. Toxicol., 25, 1868–1877 (2012). http://dx.doi.org/10.1021/tx3001658 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444623/
Liz Hajovsky, Gang Hu, Yakov Koen, Diganta Sarma, Wenqi Cui, David S. Moore, Jeff L. Staudinger and Robert P. Hanzlik, "Metabolism and Toxicity of Thioacetamide and Thioacetamide S-Oxide in Rat Hepatocytes." Chem. Res. Toxicol. 25, 1955-1963 (2012). http://dx.doi.org/10.1021/tx3002719 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444651/
Yakov M. Koen, Diganta Sarma, Heather Hajovsky, Nadezhda A. Galeva, Todd D. Williams, Jeffrey L. Staudinger and Robert P. Hanzlik, "Protein Targets of Thioacetamide Metabolites in Rat Hepatocytes" Chem. Res. Toxicol. 26, 564−574 (2013). dx.doi.org/10.1021/tx400001x. PMID 23465048 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710294/
Robert P. Hanzlik; Yakov M. Koen; Jianwen Fang, "Bioinformatic Analysis of 302 Reactive Metabolite Target Proteins. Which Ones Are Important for Cell Death?" Toxicological Sciences, 135, 390-401 (2013) doi: 10.1093/toxsci/kft166
Pinakin Sukthankar , L. Adriana Avila, Susan K. Whitaker, Takeo Iwamoto, Alfred Morgenstern, Christos Apostolidis, Ke Liu, Robert P. Hanzlik, Ekaterina Dadachova, JohnM. Tomich, "Branched amphiphilic peptide capsules: Cellular uptake and retention of encapsulated solutes" Biochimica et Biophysica Acta 1838, 2296-2305 (2014). http://dx.doi.org/10.1016/j.bbamem.2014.02.005
Yakov M. Koen, Nadezhda A. Galeva, Imir G. Metushi, Jack Uetrecht, and Robert P. Hanzlik, “Protein Targets of Isoniazid-Reactive Metabolites in Mouse Liver in Vivo.” Chem. Res. Toxicol. 2016, 29, 1064−1072. http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.6b00098
Goldman, J.L, Koen, Y,M., Rogers, S., Li, K., Leeder, S.L., Hanzlik, R. P., “Bioactivation of Trimethoprim to Protein-Reactive Metabolites in Human Liver Microsomes,”Drug Metab. Dispos. 44:1603–1607 (2016). PMID:27457783
Yakov M. Koen, Ke Liu, Heather Shinogle, Todd D. Williams, and Robert P. Hanzlik, “Comparative Toxicity and Metabolism of N‑Acyl Homologues ofAcetaminophen and Its Isomer 3′-Hydroxyacetanilide.” Chem Res Toxicol. 29, 1857-1864 (2016). PMID:27680534
Lan Lan, Minli Xing, Justin Douglas, Philip Gao, Robert P. Hanzlik, Liang Xu, "Human oncoprotein Musashi-2 N-terminal RNA recognition motif backbone assignment and identification of RNA-binding pocket." Oncotarget. 2017, 8(63), 106587-106597. PMID: 29290973 PMCID: PMC5739758 DOI: 10.18632/oncotarget.22540
Lan Lan, Minli Xing, Maithri M. Kashipathy, Justin T. Douglas, Philip Gao, Kevin P. Battaile, Robert P. Hanzlik, Scott Lovell, and Liang Xu. Crystal and Solution Structures of Human Oncoprotein Musashi-2 N-terminal RNA Recognition Motif 1. Proteins. 2019;1–11. DOI: 10.1002/prot.25836