Chaney Curriculum Vitae - UNC Gillings School of Global ...sph.unc.edu/files/2013/07/704231872_cv3.pdf3 180 Labeling Patterns and Unstable RNA Degradation in Escherichia coli, Department

Curriculum Vitae Updated April 19, 2011

Stephen G. Chaney

PERSONAL INFORMATION: Name: Stephen Gifford Chaney Business Address: 3091 Genetic Medicine Building Department of Biochemistry and Biophysics Univ. of North Carolina School of Medicine CB# 7260 Chapel Hill, NC 27599-7260 Business Telephone: (9l9) 966-3286 Fax: (919) 966-2852 Email Address: [email protected] EDUCATION: UNC Teaching Scholars Program, 1994-1995 Postdoctoral Washington University School of Medicine Fellowship American Cancer Society Postdoctoral Fellowship, 1970-1972 Research Advisor - Dr. David Schlessinger Ph.D. University of California at Los Angeles Biochemistry, September, 1970 Research Advisor - Dr. Paul D. Boyer B.S. Duke University, Durham, NC Chemistry, June, 1966

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EMPLOYMENT HISTORY: 2009-present Distinguished Professor

2005-2009 Medical Alumni Distinguished Teaching Professor

1992-present Professor of Biochemistry and Biophysics 1992-present Professor, Joint Appointment in the Department of Nutrition 1983-1992 Associate Professor of Biochemistry 1991-1992 Associate Professor, Joint Appointment in

Department of Nutrition 1972-1983 Assistant Professor of Biochemistry University of North Carolina School of Medicine Chapel Hill, NC 27514 OTHER UNC AFFILIATIONS: Department of Nutrition Lineberger Comprehensive Cancer Center Academy of Educators MAJOR AREAS OF RESEARCH INTEREST: Mechanism of action of platinum anticancer agents, DNA repair, mutagenesis. PROFESSIONAL SOCIETIES: American Association for the Advancement of Science American Chemical Society American Society for Biochemistry and Molecular Biology American Association for Cancer Research American Society for Nutrition International Association of Medical Science Educators Association of Biomolecular Course Directors, member of Executive Committee HONORS

Freshman Basic Science Teaching Award, UNC School of Medicine. Awarded by the Whitehead Medical Society for the 2002-2003 academic year.

Freshman Basic Science Teaching Award, UNC School of Medicine. Awarded by the Whitehead Medical Society for the 2004-2005 academic year.

Medical Alumni Distinguished Teaching Professorship, 9/01/05-8/30/09 UNC School of Medicine Academy of Educators, 3/27/07- present BIBLIOGRAPHY: Thesis:

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180 Labeling Patterns and Unstable RNA Degradation in Escherichia coli, Department of

Chemistry, University of California at Los Angeles, 238 pages (1970). Chapters in Textbooks:

1. Chaney SG: "Principles of Nutrition: Macronutrients" in Textbook of Biochemistry with Clinical Correlations, 6th Edition (ed by T. Devlin), Wiley, New York, 2005.

2. Chaney SG: "Principles of Nutrition: Micronutrients" in Textbook of Biochemistry with Clinical Correlations, 6th Edition (ed by T. Devlin), Wiley, New York, 2005.

Refereed Papers: Original Research: (Note: *=publications by graduate student, postdoctoral fellows or technician under direct supervision of Dr. Chaney).

1. *King, C.L., Ramachandran, S., Chaney, S.G., Collins, L., Swenberg, J.A., deKrafft, K.E., Lin, W., Cicurel, L. and Barbier, M.: “Debio 0507 Primarily Forms Pt-diaminocyclohexane-d(GpG) and –d(ApG) DNA Adducts in HCT116 Cells, manuscript in preparation.

2. *Bhattacharyya, D., Ramachandran S., Sharma S., Pathmasiri W., King, C.L., Baskerville-Abraham, I., Boysen,G., Swenberg, J.A., Campbell, S.L., Dokholyan N. V., Chaney, S.G.: “Flanking Bases Influence the Nature of DNA Distortion by Oxaliplatin 1,2-Intrastrand (GG) Cross-links”, manuscript submitted to J. Mol. Biol.

3. Chaney, SG, Pelley, JW and Seifert, WE Jr, “The Role and Value of the Basic Sciences in Medical Education (With an Emphasis on Biochemistry), J. Int. Assoc. Med. Sci. Educ., 20-3: 280-283, 2010.

4. *Baskerville-Abraham I, Boysen, G, Troutman J, Mutlu E, Collins L , deKrafft K, Lin W, King C, Chaney S and Swenberg J: “Development of an ultra performance LC/MS method to quantify cisplatin 1,2 intrastrand guanine-guanine adducts”, Chem. Res. Toxicol. 22: 905-912, 2009.

5. Shachar S, Ziv O, Avkin S, Adar S, Wittschieben J, Reissner T, Chaney S, Friedberg EC, Wang Z, Carell T, Geacintov N and Livneh Z: “Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals”, EMBO J, 28: 383-393, 2009.

6. *Ramachandran S, Temple B, Chaney SG and Dokholyan NV: “Structural basis for the sequence dependent effects of platinum-DNA adducts”, Nucl. Acids Res., 37: 2434-2448, 2009.

7. *Sharma S, Gong P, Temple B, Bhattacharyya D, Dokholyan NV and Chaney SG: “Molecular dynamic simulations of cisplatin- and oxaliplatin-d(GG) intrastrand cross-links reveal differences in their conformational dynamics”, J. Mol. Biol., 373: 1123-1140, 2007.

8. *Wu Y, Bhattacharyya D, King CL, Baskerville-Abraham I, Huh S-H, Boysen G, Swenberg JA, Temple B, Campbell S and Chaney SG: “Solution structure of a DNA dodecamer duplex with and without a cisplatin 1,2-d(GG) intrastrand cross-link: Comparison with the same DNA duplex containing an oxaliplatin 1,2-d(GG) intrastrand cross-link”, Biochemistry, 64: 6477-6487, 2007.

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9. Avkin S, Sevilya Z, Toube L, Geacintov N, Chaney SG, Oren M, and Livneh Z: “p53 and p21 regulate error-prone DNA repair (translesion DNA synthesis) to yield a lower mutation burden”, Molecular Cell, 22: 407-413, 2006.

10. *Bassett E, King NM, Bryant MF, Hector S, Pendyala L, Chaney SG and Cordeiro-Stone M: “The role of DNA polymerase in translesion synthesis past platinum-DNA adducts in human fibroblasts”, Cancer Res., 64: 6469-6475, 2004.

11. *Wu Y, Pradhan P, Havener J, Boysen G, Swenberg JA, Campbell SL and Chaney SG: “NMR solution structure of an oxaliplatin 1,2-d(GG) intrastrand cross-link in a DNA dodecamer duplex”, J. Mol. Biol., 341: 1251-1269, 2004.

12. *Bassett E, Vaisman A, Havenor JM, Masutani C, Hanaoka F, and Chaney SG: “Efficiency of extension of mismatched primer termini across from cisplatin and oxaliplatin adducts by human DNA polymerases and in vitro”, Biochemistry, 42: 14197-14206, 2003.

13. *Havener J, Nick McElhinney SA, Bassett E, Gauger, M, Ramsden, DA and Chaney SG: “Translesion synthesis past platinum DNA adducts by human DNA polymerase ”, Biochemistry, 42: 1777-1788, 2003.

14. *Bassett E, Vaisman A, McCall CM, Masutani C, Hanaoka F, and Chaney SG: “In Vitro Frequency of Frameshift and Other Errors During Translesion Synthesis Past Pt-DNA Adducts by DNA Polymerases and ”, DNA Repair, 1: 1003-1016, 2002.

15. Shord SS, Bernard SA, Lindley C, Blodgett A, Mehta V, Churchel MA, Poole M, Luo FR, Chaney SG: “Oxaliplatin Biotransformations and Pharmacokinetics: Relationship to Neurotoxicity”, Anticancer Res, 22: 2301-2309, 2002.

16. Vaisman A, Warren MW, Chaney SG: “The Effect of DNA Structure on the Catalytic Efficiency and Fidelity of Human DNA Polymerase on Templates with Platinum-DNA Adducts”, J. Biol. Chem., 276: 18999-19005, 2001.

17. Woynarowski JM, Faivre S, Herzig MCS, Arnett B, Chapman WG, Trevino AV, Raymond E, Chaney SG, Vaisman A, Varchenko, M, Juniewicz, PE: “Oxaliplatin-induced Damage of Cellular DNA”, Molec. Pharmacol. 58: 920-927, 2000.

18. Vaisman A, Masutani C, Hanaoka F, Chaney SG: “Efficient Translesion replication Past Oxaliplatin and Cisplatin GpG Adducts by Human DNA Polymerase ”, Biochemistry, 39: 4575-4580, 2000.

19. Vaisman A, Chaney SG: “The Efficiency and Fidelity of Translesion Synthesis Past Cisplatin and Oxaliplatin GpG Adducts by Human DNA Polymerase ”, J. Biol. Chem., 275: 13017-13025, 2000.

20. Vaisman A, Lim SE, Patrick SM, Copeland WC, Hinkle DC, Turchi JJ, Chaney SG: “The Effect of DNA Polymerases and HMG1 on the Carrier Ligand Specificity for Translesion Synthesis Past Pt-DNA Adducts",” Biochemistry, 38: 11026-11039, 1999.

21. Reardon JT, Vaisman A, Chaney SG, Sancar, A: “Efficient Nucleotide Excision repair of Cisplatin, Oxaliplatin, and JM216 Platinum Intrastrand DNA Diadducts”, Cancer Res., 59: 3968-3971, 1999.

22. *Luo FR, Wyrick SD, and Chaney SG: “Comparative Neurotoxicity of Oxaliplatin, Ormaplatin, and their Biotransformation Products Utilizing a Rat Dorsal Root Ganglia In Vitro Explant Culture Model” Cancer Chemotherapy & Pharmacology, 44: 29-38, 1999.

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23. *Luo FR, Wyrick SD, and Chaney SG: “Pharmacokinetics and Biotransformations of Oxaliplatin in Comparison with Ormaplatin Following a Single Bolus Intravenous Injection in Rats”. Cancer Chemotherapy & Pharmacology, 44: 19-28, 1999.

24. *Luo FR, Wyrick SD, and Chaney SG: “Biotransformations of Oxaliplatin in Rat Blood In Vitro” J. Biochem. Molec. Toxicol., 13: 159-169, 1999.

25. *Luo FR, Yan R, Wyrick SD, and Chaney SG: “High Performance Liquid Chromatographic Separation of the Biotransformation Products of Oxaliplatin”. J. Chromatog. B, 724: 345-356, 1999.

26. *Ding, H, Goldberg MM, Raymer JH, Holmes J, Stanko J, and Chaney SG: Determinations of Platinum in Rat Dorsal Root Ganglion Using ICP-MS. Biol. Tr. Element Res., 67: 1-11, 1999.

27. *Luo FR, Wyrick SD, and Chaney SG: “Cytotoxicity, Cellular Uptake, and Cellular Biotransformations of Oxaliplatin in Human Colon Carcinoma Cells” Oncol. Res., 10: 595-603, 1998.

28. Vaisman A, Varchenko M, Umar A, Kunkel T, Risinger J, Barrett JC, Hamilton TC, and Chaney SG: The Role of hMLH1, hMSH3, and hMSH6 Defects in Cisplatin and Oxaliplatin Resistance: Correlation with Replicative Bypass of Platinum-DNA Adducts, Cancer Res., 58: 3579-3585, 1998.

29. *Holmes J, Stanko J, Varchenko M, Ding H, Madden VJ, Bagnell CR, Wyrick SD and Chaney SG: Comparative Neurotoxicity of Oxaliplatin, Cisplatin, and Ormaplatin in a Wistar Rat Model, Toxicol. Sci., 46: 342-351, 1998.

30. *Vaisman, A, Varchenko, M, Saib, I and Chaney, SG: Cell Cycle Changes Associated with Formation of Pt-DNA Adducts in Human Ovarian Carcinoma Cells with Different Cisplatin Sensitivity, Cytometry, 27:54-64 (1997)

31. *Delmastro DA, Li J, Vaisman A, Solle M and Chaney SG: DNA-Damage Inducible Gene Expression Following Platinum Treatment in Human Ovarian Carcinoma Cell Lines, Cancer Chemotherap. Pharmacol., 39:245-253 (1997)

32. *Peterson, LN, Mamenta, EL, Stevnsner, T, Chaney, SG, and Bohr, VA: Increased Gene-Specific Repair of Cisplatin Induced Interstrand Crosslinks in Cisplatin Resistant Cell Lines and Studies on Carrier Ligand Specificity, Carcinogenesis, 17: 2597-2602 (1996)

33. *Vaisman A, Keeney S, Nichols AF, Linn S and Chaney SG: Cisplatin-induced Alterations in the Expression of mRNAs for UV-damage recognition protein, Oncology Res., 8: 7-12 (1996)

34. Shea T, Graham M, Bernard S, Steagall A, Wiley J, Serody J, Brecher M, Bentley S, Johnson C, Vaisman A, Chaney SG, Letrent S and Brouwer K: A Clinical and Pharmacokinetic Study of High-Dose Carboplatin, Paclitaxel, G-CSF, and Peripheral Blood Stem Cells (PBSC) in Patients with Unresectable or Metastatic Cancer, Sem. Oncol.,22:80-85 (1995)

35. *Thompson DC, Wyrick SD, Holbrook DJ and Chaney SG: HPLC and 31P NMR Characterization of the Reaction Between Antitumor Platinum Agents and the Phosophorothioate Chemoprotective Agent, WR-2721, Biochem. Pharmacol., 50:1413-1419 (1995).

36. *Thompson DC, Wyrick SD, Holbrook DJ and Chaney SG: Effect of the Chemoprotective Agent, WR-2721, on Disposition and Biotransformation of Ormaplatin in the Fischer 344 Rat Bearing a Fibrosarcoma, Cancer Res., 55:2837-2846 (1995).

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37. *Thompson DC, Wyrick SD, Holbrook DJ and Chaney SG: Effects of Anesthetics on Ormaplatin Biotransformations in the Fischer 344 Rat, Cancer Invest., 13:555-557 (1995).

38. *Vaisman A and Chaney SG: Induction of UV Damage Recognition Protein by Cisplatin Treatment, Biochemistry, 34: 105-114 (1995)

39. *Sakata M, Chaney SG and Spriggs DR: Possible Correlation between Ormaplatin Biotransformations and Neurotoxicity, Oncol. Res., 7:67-71 (1995).

40. *Thompson, DC, Vaisman A, Sakata MK, Wyrick SD, Holbrook DJ and Chaney SG: Organ-Specific Biotransformations of Ormaplatin in the Fischer 344 Rat, Cancer Chemotherap. Pharmacol., 36: 439-447 (1995).

41. Shamkhani H, Anderson LM, Henderson CE, Moskal TJ, Runowicz CD, Dove LF, Jones AB, Chaney SG, Rice JM, and Poirier MC: DNA Adducts in Human and Patas Monkey Maternal and Fetal Tissues Induced by Platinum Drug Chemotherapy, Reproduct. Toxicol., 8:207-216 (1994).

42. *Mamenta EL, Poma EE, Kaufmann WI, Delmastro DA, Grady HL and Chaney SG: Enhanced Replicative Bypass of Platinum-DNA Adducts in Cisplatin-Resistant Human Ovarian Carcinoma Cell Lines, Cancer Res., 54:3500-3505 (1994).

43. Petros WP, Chaney SG, Smith DC, Fangmeier J, Sakata M, Brown TD and Trump DL: Pharmacokinetic and Biotransformation Studies of Ormaplatin in Conjunction with a Phase I Clinical Trial, Cancer Chemotherap. Pharmacol., 33:347-354 (1994)

44. *Schmidt W and Chaney SG: Role of Carrier Ligand in Platinum Resistance of Human Carcinoma Cell Lines, Cancer Res. 53:799-805 (1993).

45. *Nichols AF, Schmidt WJ, Chaney SG and Sancar A: Limitations of the In Vitro Repair Synthesis Assay for probing the Role of DNA Repair in Platinum Resistance, Chemico-Biological Interactions, 81:223-231 (1992).

46. *Gibbons GR, Kaufmann WK and Chaney SG: Role of DNA Replication in Carrier Ligand Specific Resistance to Platinum Compounds in L1210 Cells, Carcinogenesis, 12:2253-2257 (1991).

47. *Thomas DC, Husain I, Chaney SG, Panigrahi GB and Walker IG: Sequence Effect on Incision by (A)BC Excinuclease of 4NQO Adducts and UV Photoproducts, Nucleic. Acids Res., 19:365-370 (1991).

48. *Gibbons GR, Page JD and Chaney SG: Treatment of DNA with Ammonium Bicarbonate or Thiourea Can Lead to Underestimation of Platinum-DNA Monoadducts, Cancer Chemotherap. Pharmacol., 29:112-116 (1991).

49. *Chapman DE, Holbrook DJ, Chaney SG, Hall IH and Lee KH: In vivo and In Vitro Effects of Helenalin on Mouse Hepatic Microsomal Cytochrome P-450, Biochem. Pharmacol., 41:229-235 (1991).

50. *Carfagna PF, Wyrick SD, Holbrook DJ, and Chaney SG: Effects of Diethyldithiocarbamate (DDTC) on the Plasma Biotransformations of Tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum(IV) (Tetraplatin) in Fischer 344 Rats, J. Biochem. Toxicol, 6:71-80, 1991.

51. *Carfagna PF, Poma A, Wyrick SD, Holbrook DJ, and Chaney SG: Comparisons of Tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum(IV) (Tetraplatin) Biotransformations in the Plasma of Fischer 344 Rats at Therapeutic and Toxic Doses, Cancer Chemotherap. Pharmacol., 27:335-341, 1991.

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52. Chaney SG, Gibbons GR, Wyrick, SD, and Podhasky P: An Unexpected Biotransformation Pathway for Tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum(IV) (Tetraplatin) in the L1210 Cell Line, Cancer Res., 51:969-973 (1991).

53. Oswald CB, Chaney SG and Hall IH: Inhibition of Nucleic Acid Synthesis in P-388; Lymphocytic Leukemia Cells in Culture by Cis-platinum Derivatives, Biomed. Biochim. Acta, 49:579-587 (1990).

54. Hall IH, Grippo AA, Holbrook DJ, Chang JJ, Yang LM, Chaney SG, and Lee KH: Renal, Hepatic, Cardiac and Thymic Acute Toxicity Afforded by bis(Helenalinyl)malonate in BDF1 Mice, Toxicology, 64:205-216 (1990).

55. Chaney SG, Wyrick S, and Till GK: In Vitro Biotransformations of Tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum(IV) (Tetraplatin) in Rat Plasma, Cancer Res., 50:4539-4545 (1990).

56. *Gibbons GR, Page JD, Mauldin SK, Husain I, and Chaney SG: Role of Carrier Ligand in Platinum Resistance in L1210 Cells, Cancer Res., 50:6497-6501 (1990).

57. Oswald CB, Chaney SG and Hall IH: Inhibition of DNA Synthesis in P388 Lymphocytic Leukemia Cells of BDF1 Mice by Cis-Diamminedichloroplatinum(II) and Its Derivatives, J. Pharm. Sci., 79:875-880 (1990).

58. *Wyrick SD, and Chaney SG: Synthesis of [195mPt] Tetraplatin, J. Labeled Compounds and Radiopharmaceuticals, 28:753-756 (1990).

59. Rosenblum MG, Murray JL, Stuckey S, Newman RA, Chaney S, and Khokar AR: Modification of Methylminiodiacetato-trans-R,R-1,2-Diamminocyclohexane Platinum (II) (MIDP) Pharmacology using a Platinum-Specific Monoclonal Antibody,Cancer Chemotherap. Pharmacol, 25:405-410 (1990).

60. *Carfagna PF, Chaney SG, Chang J and Holbrook DJ: Reduction of Tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum(IV) (Tetraplatin) Toxicity by Administration of Diethyldithiocarbamate (DDTC), S-2(3-aminopropylamine)ethylphosphorothioic acid (WR-2721) or Sodium Selenite in the Fischer-344 Rat, Fundam. Appl. Toxicol. 14:706-719 (1990).

61. *Page JD, Husain I, Sancar A, and Chaney SG: Effect of the Diaminocyclohexane Carrier Ligand on Platinum Adduct Formation, Repair, and Lethality, Biochemistry, 29:1016-1024 (1990).

62. Disposition of Cisplatin Derivatives 3H-cis-1,2-Diaminocyclohexanedichloroplatinum(II) and 3H-cis-1,2-Diaminocyclohexanemalonatoplatinum(II) in BDF1 Mice, Research Comm. Chem. Path. Pharm., 64:41-58 (1989).

63. *Chapman DE, Holbrook DJ, Chaney SG, Hall IH, and Lee KH: In Vitro Inhibition of Mouse Hepatic Mixed Function Oxidase Enzymes by Helenalin and Allantolactone, Biochemical Pharmacology, 38:3913-3923 (1989).

64. *Gibbons G, Wyrick S, and Chaney SG: Rapid Reduction of Tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum (IV) (Tetraplatin) in Tissue Culture medium, Cancer Res., 49:1402-1407 (1989).

65. *Mauldin SK, Gibbons G, Wyrick SD, and Chaney SG: Intracellular Biotransformation of Platinum Compounds with the 1,2-Diaminocyclohexane Carrier Ligand in the L1210 Cell Line, Cancer Res., 48:5136-5144 (1988).

66. *Mauldin SK, Plescia M, Richard FA, Wyrick SG, Voyksner RD, and Chaney SG: Displacement of the Malonate Ligand from (d,l-trans-1,2-

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Diaminocyclohexane)malonatoplatinum(II) by Physiologically Important Compounds In Vitro, Biochemical Pharmacology, 37:3321-3333 (1988).

67. *Chaney SG, Mauldin SK, and Gibbons G: Biotransformations of Platinum Compounds with the 1,2-Diaminocyclohexane Carrier Ligand in Cultured L1210 Leukemia Cells, in Platinum and Other Metal Coordination Compounds In Cancer Chemotherapy (ed by M. Nicolini), pp. 290-300, Martinus Nijhoff Publishing, Boston, 1988.

68. *Page JD, Husain I, Chaney SG, and Sancar A: In Vitro Repair of Cisplatin-DNA Adducts by a Defined Enzyme System, in Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy (ed by M. Nicolini), pp. 115-126, Martinus Nijhoff Publishing, Boston, 1988.

69. *Wyrick SD and Chaney SG: Tritiated Platinum Antitumor Agents Containing the Trans(d,l)-1,2-Diaminocyclohexane Carrier Ligand, J. Labeled Compounds and Radiopharmaceuticals, 25:349-357 (1988).

70. Williams WL, Jr., Hall IH, Grippo AA, Oswald CB, Lee KH, Holbrook DJ, and Chaney SG: Inhibition of Nucleic Acid Synthesis in P-388 Lymphocytic Leukemia Tumor Cells by Helenalin and Bis(helenalinyl)malonate In vivo, J. Pharm. Sci., 77:178-184 (1988).

71. Hall IH, Williams WL, Jr., Grippo AA, Lee KH, Holbrook DJ, and Chaney SG: Inhibition of Nucleic Acid Synthesis in P-388 Lymphocytic Leukemia Cells in Culture by Sesquiterpene Lactones, Anticancer Research, 8:33-42 (1988).

72. *Chapman DE, Roberts GB, Reynolds DJ, Grippo AA, Holbrook DJ, Hall IH, Chaney SG, Chang J, and Lee KH: Acute Toxicity of Helenalin in BDFI Mice, Fundamental and Applied Toxicology, 10:302-312 (1988).

73. Hall IH, Grippo AA, Lee KH, Chaney SG, and Holbrook DJ: Effect of Helenalin and Bis(helenalinyl) Malonate on Nucleic Acid and Protein Synthesis in Human KB Carcinoma Cells, Pharmaceut. Res., 4:509-514 (1987).

74. *Page JD, Chaney SG, Hall IH, Lee KH, and Holbrook DJ: Inhibition of Inosine Monophosphate Dehydrogenase by Sesquiterpene Lactones, Biochim. Biophys. Acta. 926:186-194 (1987).

75. *Mauldin SK, Richard FA, Plescia M, Wyrick SD, Sancar A, and Chaney SG: High Performance Liquid Chromatographic Separation of Platinum Complexes Containing the cis-1,2-Diaminocyclohexane Carrier Ligand, Anal. Biochem., 157:129-143 (1986).

76. *Mauldin SK, Husain I, Sancar A, and Chaney SG: Effects of the Bidentate Malonate Ligand on the Utilization and Cytotoxicity of Platinum Compounds in the L1210 Cell Line, Cancer Res., 46:2876-2882 (1986).

77. *Husain, I., Chaney, SG, and Sancar, A: Repair of Cis Platinum - Deoxyribonucleic Acid Adducts By ABC Excinuclease In vivo and In Vitro. J. Bact., 163:817-823 (1985).

78. Hall, IH, Williams, WL, Chaney, SG, Gilbert, CJ, Holbrook, DJ, Muraoka, O., Kiyokowa, H, and Lee, KH: Antitumor Agents 68: Effects of a Series of Helenalin Derivatives on P-388 Lymphocytic Leukemia Nucleic Acid and Protein Synthesis, J. Pharm Sci., 74:250-254 (1985).

79. Chaney SG, Williams WL, Willingham W, Considine RT, Hall IH, and Lee K-H: Inhibition of Protein Synthesis Initiation Factors by Naturally Occurring Sulfhydryl Reactive Reagents, Current Topics in Cellular Regulation, 24:251-260 (1984).

80. *Williams WL, Chaney SG, Hall IH, Lee KH: Indirect Inactivation of Rabbit Reticulocyte Initiation Factor eIF-2 by Helenalin and Bis-helenalinyl Malonate. Biochemistry, 23:5637-5644 (1984).

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81. *Willingham Jr., W, Considine RT, Chaney SG, Lee KH, Hall IH: Reversibility of Protein Synthesis Inhibition by Quassinoid Antineoplastic Agents in a Rabbit Reticulocyte System. Biochem. Pharmacol, 33:330-333 (1984).

82. *Considine RT, Willingham Jr., W, Chaney SG, Wyrick S, Hall IH, Lee KH: Structure Activity Relationships for Binding and Inactivation of Rabbit Reticulocyte Ribosomes by Quassinoid Antineoplastic Agents. Eur J. Biochem, 132:157-163 (1983).

83. *Williams WL, Chaney SG, Willingham W, Considine RT, Hall IH, Lee KH: Selective Inactivation of Rabbit Reticulocyte Initiation Factor eIF-3 by Helenalin. Biochim Biophys Acta, 740:152-162 (1983).

84. Hall IH, Liou YF, Lee KH, Chaney SG, Willingham W: Antitumor Agents 59. The Effect of Quassinoids on Protein Synthesis of Murine Tumors and Related Tissues. J Pharm Sci, 72:626-630 (1983).

85. *Williams DE, Jackson JM, Chaney SC: Characterization of RNA Synthesis in a Mutant Strain of E. coli with a Temperature Sensitive Lesion in Stable RNA Synthesis. J Bacteriol 153:616-626, 1983.

86. Liou YF, Hall IH, Lee KH, Williams WL, Chaney SG: Investigation of Sesquiterpene Lactones as Protein Synthesis Inhibitors of P-388 Lymphocytic Leukemia Cells. Biochim. Biophys. Acta, 739:190-196 (1983).

87. *Reynolds SH, Brantley CK, Harris, JS, Chaney, SG: ppGpp Levels, Carbon Source, and RNA Synthesis in a Mutant Strain of Escherichia coli. Biochemistry 22:1123-1128, 1983.

88. *Reynolds SH, Chaney SG: Carbon Source Transport, Nucleotide Levels, and Stable RNA Synthesis in a Mutant Strain of E. coli. Arch Biochem Biophys 221:548-556, 1983.

89. Liou YF, Hall IH, Okano M, Lee KH, Chaney SG: Antitumor Agents 48: Structure-Activity Relationships of Quassinoids as In Vitro Protein Synthesis Inhibitors of P-388 Lymphocytic Leukemia Cell Metabolism. J Pharm Sci, 71:430-435, 1982.

90. Hall IH, Liou YF, Lee KH, Okano M, Chaney SG: Antitumor Agents 47: The Effects of Bisbrusatolyl Malonate on P-388 Lymphocytic Leukemia Cell Metabolism. J Pharm Sci 71:257-262, 1982.

91. *Willingham Jr, W, Stafford EA, Reynolds SH, Chaney SG, Lee KH, Okano M,Hall IH: Mechanism of Eukaryotic Protein Synthesis Inhibition by Brusatol. Biochim Biophys Acta 654:169-174, 1981.

92. *Harris JS, Chaney SG: Guanine Nucleotide Metabolism in a Mutant Strain of Escherichia coli with a Temperature Sensitive Lesion in rRNA Synthesis. Biochim Biophys Acta 521:634-640, 1978.

93. *Harris JS, van Tassel E, Chaney SG: A Mutation in Escherichia coli that Mimics Diauxie Lag. Biochem Biophys Res Commun 82:982-989, 1978.

94. Chaney SG, Jackson JM, III, Harris JS: A New Mutation Affecting Ribosomal RNA Synthesis in Escherichia coli. Biochemistry 16:3603-3607, 1977

95. *Jackson JM, III, Chaney SG: Escherichia coli Mutants with Altered Ribosomal Ribonucleic Acid Metabolism. J Bacteriol 125:1057-1073, 1976.

96. Chaney SG, Schlessinger D: Escherichia coli Mutants Deficient in RNA Accumulation at High Temperature. Biochim Biophys Acta 378:80-91, 1975.

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97. Chaney SG, Duffy JJ, Boyer PD: Patterns of Oxygen Interchange between Water, Substrates, and Phosphate Compounds of Escherichia coli and Bacillus subtilus. J Biol Chem 247:2145-2150, 1972.

98. Chaney SG, Boyer PD: Incorporation of Water Oxygens into Intracellular Nucleotides and RNA. II. Hydrolytic RNA Turnover in Escherichia coli. J Mol Biol 64:581-591, 1972.

99. Duffy JJ, Chaney SG, Boyer PD: Incorporation of Water Oxygens into Intracellular Nucleotides and RNA. I. Non-Hydrolytic RNA Turnover in Bacillus subtilis. J Mol Biol 64:565-579, 1972.

100. Chaney SG, Boyer PD: Lack of Detection of Intermediates in the Path of Phosphate Oxygen to Water in Photophosphorylation. J Biol Chem 244:5773-5776, 1969.

Other Peer Reviewed Articles (Reviews):

1. Chaney SG, Ramachandran S, Sharma S, Dokholyan NV, Temple B, Bhattacharyya D, Wu Y and Campbell S: Differences in Conformation and Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts, in Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy,Molecular Mechanisms and Clinical Implications (A Bonetti, F Muggia R. Leone and SB Howell, eds), Humana Press, Totowa, NJ, pp. 157-169, 2009.

2. Chaney SG, Campbell SL, Bassett E and Wu Y: Recognition and Processing of Cisplatin- and Oxaliplatin-DNA Adducts, Crit. Rev. Oncol. Hematol., 53: 3-11, 2005.

3. Chaney SG, Campbell SL, Temple B, Bassett, E, Wu Y and Faldu M: Protein Interactions with Platinum-DNA Adducts: From Structure to Function, J. Inorg. Biochem., 98: 1551-1559, 2004.

4. Mani S, Bregman D, Ivy P, Wadler S, Chaney S: Oxaliplatin: A Review of Evolving Concepts, Cancer Invest., 20: 246-263, 2002

5. Raymond E, Faivre S, Chaney S, Woynarowski J, Cvitkovic,E: Cellular and Molecular Pharmacology of Oxaliplatin, Mol. Cancer Ther., 1: 227-235 (2002).

6. Vaisman A and Chaney SG: DNA Adduct Tolerance and Bypass, in Platinum-based Drugs in Cancer Therapy (LR Kelland and NP Farrell eds) Humana Press, Totowa, NJ, pp. 129-148, 1999.

7. Chaney SG and Vaisman A: Specificity of Platinum DNA Adduct Repair, J. Inorg. Biochem.,77: 71-81, 1999

8. Raymond E, Faivre S, Woynarowiski JM, and Chaney SG: Oxaliplatin: Mechanism of Action and Antineoplastic Activity, Sem. Oncol., 25: Supp 5: 4 -12 , 1998

9. Chaney S, Raymond E, Taamma A, and Cvitkovic E: Preclinical and Clinical Studies of Oxaliplatin. Annals Oncol., 9: 1053-1071, 1998.

10. Chaney SG and Mamenta EL: DNA Repair and the Carrier Ligand Specificity of Platinum Resistance, in Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, 2 (HM Pinedo and JH Schornagel, eds) pp. 327-340, Plenum Press, New York, 1996.

11. Chaney, SG and Sancar, A: DNA Repair-Enzymatic Mechanisms and Relevance to Drug Response, J. Natl. Cancer Inst., 88: 1346-1360, 1996.

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12. Chaney SG: The Chemistry and Biology of Platinum Complexes with 1,2-Diaminocyclohexane Carrier Ligand, Int. J. Oncol., 6:1291-1305, 1995.

13. Chaney SG, Gibbons GR, Schmidt W and Page JD: Carrier Ligand Effects in Platinum Resistant Cell Lines, in Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy (SB Howell, ed), pp. 269-283,Plenum Press, New York, 1991.

Chapters in Textbooks:

1. Chaney SG: "Vitamins and Minerals: Requirements and Function" in Textbook of Biochemistry with Clinical Correlations, 7th Edition (ed by T. Devlin), Wiley, New York, 2009.

2. Chaney SG: "Macronutrients: Metabolic Effects and Health Implications" in Textbook of

Biochemistry with Clinical Correlations, 7th Edition (ed by T. Devlin), Wiley, New York, 2009.

3. Chaney SG: "Principles of Nutrition I: Macronutrients" in Textbook of Biochemistry

with Clinical Correlations, 6th

Edition (ed by T. Devlin), Wiley-Liss, New York, 2006. 4. Chaney SG: "Principles of Nutrition II: Micronutrients" in Textbook of Biochemistry with

Clinical Correlations, 6th

Edition (ed by T. Devlin), Wiley-Liss, New York, 2006.

5. Chaney SG: "Principles of Nutrition I: Macronutrients" in Textbook of Biochemistry with Clinical Correlations, 5

th Edition (ed by T. Devlin), Wiley-Liss, New York, 2001.

6. Chaney SG: "Principles of Nutrition II: Micronutrients" in Textbook of Biochemistry with

Clinical Correlations, 5th

Edition (ed by T. Devlin), Wiley-Liss, New York, 2001

7. Chaney SG: "Principles of Nutrition I: Macronutrients" in Textbook of Biochemistry with Clinical Correlations, 4

th Edition (ed by T. Devlin), Wiley-Liss, New York, 1997

8. Chaney SG: "Principles of Nutrition II: Micronutrients" in Textbook of Biochemistry with

Clinical Correlations, 4th

Edition (ed by T. Devlin), Wiley-Liss, New York, 1997.

9. Chaney SG: "Principles of Nutrition I: Macronutrients" in Textbook of Biochemistry with Clinical Correlations, 3

rd Edition (ed by T. Devlin), John Wiley & Sons, New York,

1992 10. Chaney SG: "Principles of Nutrition II: Micronutrients" in Textbook of Biochemistry with

Clinical Correlations, 3rd

Edition (ed by T. Devlin), John Wiley & Sons, New York, 1992.

11. Chaney SG: "Principles of Nutrition I: Macronutrients" in Textbook of Biochemistry

with Clinical Correlations, 2nd

Edition (ed by T. Devlin), John Wiley & Sons, New York, 1986

12. Chaney SG: "Principles of Nutrition II: Micronutrients" in Textbook of Biochemistry with

Clinical Correlations, 2nd

Edition (ed by T. Devlin), John Wiley & Sons, New York, 1986.

13. Chaney SG: "Principles of Nutrition I: Macronutrients" in Textbook of Biochemistry

with Clinical Correlations (ed by T. Devlin), John Wiley & Sons, New York, 1982.

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14. Chaney SG: "Principles of Nutrition II: Micronutrients" in Textbook of Biochemistry with

Clinical Correlations (ed by T. Devlin), John Wiley & Sons, New York, 1982.

Published Abstracts:

1. Ramachandran S, Temple B, Dokholyan N and Chaney SG: “The effect of

conformational dynamics of cisplatin- and oxaliplatin-DNA adducts on the binding of DNA damage recognition proteins such as HMGB1”, Proc. Am. Assoc. Cancer Res., 50: (2009), Abstract nr 4528.

2. Ramachandran S, Bhattacharyya D, Dolkholyan NV and Chaney SG: “Effects of sequence context on conformational dynamics of DNA adducts of platinum anticancer drugs: MD simulations of cisplatin- and oxaliplatin-DNA adducts”, Proc. Am. Assoc. Cancer Res., 49: (2008), Abstract nr 3279.

3. Bhattacharyya D, King CL, Sharma S, Temple B, Campbell SL and Chaney SG: Effect of sequence context on platinum-DNA adducts, Proc. Am. Assoc. Cancer Res., 48: 752-753 (2007)

4. Gong P, Bhattacharyya D, Dokholyan NV, Temple B and Chaney SG: The updated force field parameters for molecular modeling of cisplatin and oxaliplatin adducts with DNA, Proc. Am. Assoc. Cancer Res., 47: 369 (2006)

5. Gong P, Hege A, Bhattacharyya D, Dolkholyan N, Temple B and Chaney SG: A computational approach for structural elucidation of cisplatin and oxaliplatin adducts with DNA, Proc. Am. Assoc. Cancer Res., 46: 1139 (2005)

6. Wu Y, Bhattacharyya D, Campbell SL, Temple B and Chaney SG: Determination and comparison of NMR structures of cisplatin and oxaliplatin adducts with a dodecamer, Proc. Am. Assoc. Cancer Res., 46: 1138 (2005)

7. Wu Y, Havener J, Campbell S, and Chaney SG: NMR studies of cisplatin and oxaliplatin 1,2-d(GG) intrastrand cross-links and undamaged DNA in the AGG sequence context, Proc. Am. Assoc. Cancer Res., 45: 435 (2004)

8. Faldu M, Temple B, Chaney SG: Molecular dynamics simulations of DNA containing an oxaliplatin 1,2-d(GG) intrastrand cross-link in the active site of DNA polymerase beta, Proc. Am. Assoc. Cancer Res., 45: 435 (2004).

9. Basset, EV, King, NM, Bryant, MF, Cordeiro-Stone, M, Chaney, SG: DNA polymerase may not be essential for translesion synthesis past cisplatin adducts in human fibroblasts, Proc. Am. Assoc. Cancer Res., 44: 378 (2003).

10. Wu, Y, Pradhan, P, Havener, J, Campbell, SL, Chaney, SG: NMR solution structure of an oxaliplatin 1,2-d(GG) intrastrand cross-link in a DNA dodecamer duplex, Proc. Am. Assoc. Cancer Res., 44: 83 (2003).

11. Bassett, EV, Vaisman A, Cordeiro-Stone, M., Masutani, C., Hanaoka, F., Chaney, SG: In vitro and in vivo fidelity of translesion synthesis past cisplatin and oxaliplatin adducts by DNA polymerase , Proc. Am. Assoc. Cancer Res., 43: 695 (2002)

12. Gauger, M., Bassett, E., McElhiiny, SN, Ramsden, D., Chaney, SG: Translesion synthesis past platinum-DNA adducts by human DNA polymerase , Proc. Am. Assoc. Cancer Res., 43: 694 (2002)

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13. Havener, J., Diener, S., Chaney, SG: Ku and ATM appear to be required for synergy between tirapazamine (TPZ) and cisplatin (CP), Proc. Am. Assoc. Cancer Res., 43: 587 (2002)

14. Warren, M., Bassett, E., Lawlor, J., Masutani, C., Hanaoka, F., and Chaney, S.G.: Comparison of ZD0473- and cisplatin-DNA-adducts with respect to DNA damage recognition, translesion synthesis, and mismatch repair, Proc. Am. Assoc. Cancer Res., 42: 570 (2001).

15. Bassett, E., Vaisman, A., Masutani, C., Chaney, S.G., and Hanaoka, F.: In vitro and in vivo fidelity of translesion synthesis past Pt-DNA adducts by DNA polymerases and , Proc. Am. Assoc. Cancer Res., 42: 570 (2001).

16. Schifflet, S.L., Bernard, S.A., Lindley, C., Churchel, M.A., Mehta, V., Pescatore, S., and Chaney, S.G: A preliminary analysis of possible relationship of oxaliplatin and its biotransformation products to neurotoxicity, Proc. Am. Assoc. Cancer Res., 41: 706 (2000).

17. Vaisman, A., Chaney, S.G: Translesion Synthesis Past Cisplatin and Oxaliplatin GpG Adducts by Human DNA Polymerase , Proc. Am. Assoc. Cancer Res., 41: 261 (2000)

18. Vaisman A., Patrick, S.M., Tuchi, J.J., and Chaney, S,G.: Carrier ligand specificity of HMG1-mediated inhibition of in vitro replicative bypass of platinum-DNA adducts by reverse transcriptase, Proc. Am. Assoc. Cancer Res., 40: 672 (1999).

19. Vaisman A, Varchenko M, Umar A, Kunkel TA, Risinger JL, Barrett JC and Chaney SG: Defects in hMSH6, but not in hMSH3, correlate with Enhanced Replicative Bypass of Cisplatin, but not Oxaliplatin, Adducts, Proc. Am. Assoc. Cancer Res., 39: 159 (1998).

20. Luo FR, Stanko J, and Chaney SG: Pharmacokinetic and Neurotoxicological Comparison of Oxaliplatin, Ormaplatin, and their Biotransformation Products, Proc. Am. Assoc. Cancer Res., 39: 596 (1998).

21. Stanko J, Luo FR, Holmes J, Ding H and Chaney SG: Comparative In Vivo and In Vitro Neurotoxicity of Cisplatin, Oxaliplatin, and Ormaplatin in Wistar Rats, Proc. Am. Assoc. Cancer Res., 39: 596 (1998).

22. Luo F, Holmes J, and Chaney SG: In Vitro Partitioning and Biotransformations of Oxaliplatin in Rat Blood and RPMI-1640 Medium, Proc. Am. Assoc. Cancer Res., 38: 311 (1997).

23. Vaisman A, Varchenko M, and Chaney SG: Correlation Between Mismatch Repair Defects and Increased Replicative Bypass in Cisplatin Resistant Cell Lines, Proc. Am. Assoc. Cancer Res., 38: 312 (1997)

24. Holmes J, Stanko J, Nace C, Crofton K, and Chaney SG: Comparative Neurotoxicity of Cisplatin Oxaliplatin and Ormaplatin in Wistar Rats, Proc. Am. Assoc. Cancer Res., 38: 4 (1997)

25. Mamenta, EL, Vaisman A, Varchenko M and Chaney SG: Replicative Bypass of Platinum Monoadducts in a Cisplatin-Resistant Human Ovarian Carcinoma Cell Line, Proc. Am. Assoc. Cancer Res., 37: 404 (1996)

26. Delmastro D, Li J, DeMars L and Chaney SG: Gadd 153 mRNA Expression and Half-life in Sensitive and Resistant Ovarian Carcinoma Cell Lines After Treatment with Cisplatin, Proc. Am. Assoc. Cancer Res., 36:348 (1995).

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27. Mamenta EL and Chaney SG: Mechanism of Cross-Resistance to Alkylating Agents in a Cisplatin-resistant Human Ovarian Carcinoma Cell Line, Proc. Am. Assoc. Cancer Res., 36:374 (1995).

28. Vaisman A and Chaney SG: Effect of Cisplatin Treatment on Expression of the Genes Involved in DNA Nucleotide Excision Repair, Proc. Am. Assoc. Cancer Res., 36:156 (1995).

29. Thompson DC, Holbrook DJ and Chaney SG: Effects of WR-2721 on Ormaplatin (OP) Biotransformations in Tumor-Bearing Fischer 344 Rats, Proc. Am. Assoc. Cancer Res., 36:400 (1995).

30. Vaisman A and Chaney SG: Cisplatin Inducibility of UV-Damage Recognition Protein, Proc. Am. Assoc. Cancer Res., 35:440 (1994).

31. Sakata M, Delmastro D, Chaney SG, Tutsch K and Spriggs DR: Possible Correlation Between Ormaplatin Biotransformations and Neurotoxicity, Proc. Am. Assoc. Cancer Res., 35:428 (1994).

32. Thompson DC, Holbrook DJ and Chaney SG: HPLC Characterization of Organ-Specific Biotransformations of Ormaplatin in Tumor-Bearing Rats Protected with WR-2721, Proc. Am. Assoc. Cancer Res., 35:439 (1994).

33. Delmastro D, Li J, DeMars L and Chaney SG: Expression of gadd153 mRNA in Sensitive and Resistant Human Ovarian Carcinoma Cell Lines after Treatment with Cisplatin, Proc. Am. Assoc. Cancer Res., 35:439 (1994).

34. Mamenta EL, Grady HL and Chaney SG: Specificity of the Replicative Bypass Response to DNA Adducts in a Cisplatin-Resistant Human Ovarian Carcinoma Cell Line, Proc. Am. Assoc. Cancer Res., 35:440 (1994).

35. Mamenta EL, Peterson LN, Stevnsner T, Bohr VA and Chaney SG: Carrier Ligand Specificity for Genomic and Gene-Specific Repair of Platinum Interstrand Crosslinks in Murine Luekemia Cells, Proc. Am. Assoc. Cancer Res., 35:440 (1994).

36. Sakata M, Chaney SG, Fangmeier J, Petros WP, Brown T: Pharmacokinetic and biotransformation studies of ormaplatin (NSC 363812) in conjunction with a phase I clinical trial, Proc. Am. Assoc. Cancer Res., 34:164 (1993).

37. Thompson DC, Vaisman AM, Benfield BP, Wyrick SD, Holbrook DJ, Chaney SG: Loss of carrier ligand by ormaplatin In vivo: Analysis of possible binding sites for dissociated platinum, Proc. Am. Assoc. Cancer Res., 34:106 (1993).

38. Mamenta EL, Poma EE, Delmastro D, Chaney SG: Carrier ligand specificity of replicative bypass in two cisplatin-resistant human ovarian carcinoma cell lines, Proc Am. Assoc. Cancer Res., 34:24 (1993).

39. Trump DL, Petros W, Chaney SG, Smith DC, Fangmeier J, Brown TD and Goldberg H: Phase I clinical trial and study of the pharmacokinetics (PK) and metabolism of ormaplatin (tetraplatin, NSC 363812). Proc. Am. Assoc. Cancer Res., 33:538 (1992).

40. Thompson DC, Holbrook DJ, and Chaney SG: Biotransformation of Ormaplatin in the Fischer 344 rat. Proc. Am. Assoc. Cancer Res., 33:536 (1992).

41. Mamenta EL, Poma EE, and Chaney SG: Evidence of enhanced replicative bypass of platinum-DNA adducts in platinum resistant A2780 cells. Proc. Am. Assoc. Cancer Res., 33:536 (1992).

42. Gibbons GR and Chaney SG: Role of DNA Replication in Carrier Ligand Specific Resistance to Platinum Compounds in L1210 Cells, Proc. Am. Assoc. Cancer Res., 32:358 (1991).

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43. Schmidt WJ and Chaney SG: Carrier Ligand Effects on Platinum Resistance in Human Cell Lines: Cytotoxicity, Uptake, DNA Adduct Formation and Repair, Proc. Am. Assoc. Cancer Res., 32:356 (1991).

44. Gibbons GR, Page JD, Mauldin SK, Husain I, and Chaney SG: Role of Carrier Ligand in Platinum Resistance in L1210 Cells. Proc. Am. Assoc. Cancer Res., 31:331 (1990).

45. Gibbons GR, Page JD, Schmidt W, Chaney SG, and Sancar A: Effect of Carrier Ligand on the Repair of Platinum-DNA Adducts. Proc. Am. Assoc. Cancer Res., 30:488 (1989).

46. Chaney SG, Kaun-Till G, Poma A, and Holbrook DJ: Biotransformations of Tetraplatin in Rat Plasma. Proc. Am. Assoc. Cancer Res., 30:470 (1989).

47. Carfagna PF, Chaney SG, Chang J, and Holbrook DJ: Protection Against Tetraplatin Toxicity in the Fischer 344 Rat. Proc. Am. Assoc. Cancer Res., 30:470 (1989).

48. Gibbons G, Chaney SG and Holbrook DJ: Intracellular Biotransformations of Tetraplatin in the L1210 Cell Line. Proc. Am. Assoc. Cancer Res., 30:461 (1989).

49. Gibbons GR and Chaney SG: Biotransformation of Tetraplatin in Tissue Culture. Proc. Am. Assoc. Cancer Res., 29:336 (1988).

50. Page JD, Thomas DC, Chaney SG, and Sancar A: Repair of Specific Platinum-DNA Adducts. Proc. Am. Assoc. Cancer Res., 29:343 (1988).

51. Mauldin SK, Gibbons GR, and Chaney SG: Quantitation of Aquated Platinum Complexes Inside the Cell. Proc. Am. Assoc. Cancer Res., 28:315 (1987).

52. Page JD, Chaney SG, Hall IH, Lee KH, and Holbrook DJ: Inhibition of Inosine Monophosphate Dehydrogenase by Sesquiterpene Lactones. Fed Proc. 45:1612 (1986).

53. Husain I, Mauldin SK, Sancar A, and Chaney SG: The Effect of the Carrier Ligand on the Lethality of Platinum DNA Adducts. Proc. Am. Assoc.Cancer Res. 27:287 (1986).

54. Mauldin SK, Richard FA, Plescia M., and Chaney SG: High Performance Liquid Chromatographic Separation of Platinum Complexes Containing the 1,2-Diaminocyclohexane Carrier Ligand. Proc. Am. Assoc. Cancer Res. 27:286(1986).

55. Mauldin SK, and Chaney SG: Characterization and Quantitation of the Intracellular Metabolites of Some Second Generation cis-Platinum Antitumor Drugs. Fed. Proc. 43:1941 (1984).

56. Willingham WW, and Chaney SG: Mechanism of Protein Synthesis Inhibition by Brusatol and Related Quassinoids. Fed. Proc., 40: 1847 (1981).

57. Reynolds SH, and Chaney SG: Stable RNA Synthesis in a Mutant Strain of Escherichia Coli. Fed. Proc.,39: 2110 (1980).

58. Harris JS, Chaney SG: A New Mutation Affecting the Metabolism of ppGpp (Guanosine 5' Diphosphate 3' Diphosphate). Fed Proc 35:1582, 1976.

59. Chaney SG: A Mutation Affecting Ribosomal RNA Synthesis in E. coli. Fed Proc 34:707, 1975.

Papers in Press or Submitted:

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1. *Bhattacharyya D, King CL, Baskerville-Abraham I, Boysen G, Swenberg JA, Campbell S and Chaney SG: “Effect of Sequence Context on Platinated-DNA Adducts”, manuscript submitted to Biochemistry.

Refereed Unpublished Oral Presentations and Abstracts:

1. “Differences in Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts May Explain the Recognition of These Adducts by Cellular Proteins”, Gordon Research Conference on DNA Damage, Mutagenesis and Cancer, Ventura, March 12, 2008.

2. “Effects of Sequence Context on Conformational Dynamics of DNA Adducts of Platinum Anticancer Drugs: MD Simulations of Cisplatin- and Oxaliplatin-DNA Adducts”, 10

th

International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy, Verona, Italy, December 1 (2007)

3. “Differences in Conformation and Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts”, 10

th International Symposium on Platinum Coordination

Compounds in Cancer Chemotherapy, Verona Italy, December 1, 2007.

4. “A Structural Insight Into the Discrimination of Platinated DNA Adducts Shown by DNA Polymerases”, Gordon Research Conference on DNA Damage, Mutation and Cancer, Ventura, March 6 (2006)

5. “NMR and MD Structures of Cisplatin- and Oxaliplatin-GG DNA Adducts and the Implications for Translesion DNA Synthesis”, American Society for Microbiology DNA Repair Meeting, November 16 (2004)

6. “Translesion DNA Synthesis Past Platinum-DNA Adducts by DNA Polymerase ”, American Society for Microbiology DNA Repair Meeting, November 16 (2004)

7. “NMR Solution Structure of an Oxaliplatin 1,2-d(GG) Intrastrand Adduct and Molecular Dynamic Simulations of the Adduct in the Active Site of DNA Polymerase ”, Gordon Conference on DNA Repair and Mutagenesis, Ventura, March 9 (2004)

8. “NMR and MD Solution Structure of an Oxaliplatin 1,2-d(GG) Intrastrand Cross-Link in a DNA Dodecamer Duplex: From Structure to Function”, 9

th International

Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, New York, October 9 (2003)

9. “Carrier Ligand Specificity of in Vitro Replicative Bypass of Platinum-DNA Adducts by DNA Polymerases” (A. Vaisman, presenter): 8

th International Symposium on

Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, Oxford, England, March 29, 1999.

10. “Comparative Pharmacokinetics, Neurotoxicity, and Cytotoxicity of Oxaliplatin, Ormaplatin, and their Major Biotransformation Products”, 8

th International

Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, Oxford, England, March 29, 1999.

11. "Role of DNA Replication in Carrier Ligand Specific Resistance to Platinum Compounds in L1210 Cells", Sixth International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, January, 1991.

12. "Characterization of Carrier Ligand Effects on Platinum Resistance in Two Human Carcinoma Cell Lines: Cytotoxicity, Uptake, DNA Adduct Formation and Repair",

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Sixth International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, January, 1991.

13. "Biotransformations of Platinum Compounds with the 1,2-Diaminocyclohexane Carrier Ligand in Cultured L1210 Leukemia Cells," Fifth International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, Padua, Italy, July, 1987.

Presentations at Educational Meetings:

1. "Educational Uses of Audience Response Systems", Association of Biochemistry Course Directors, Myrtle Beach, April 26 (2009).

2. "Ideas For Being A Highly Effective Course Director", Association of Biochemistry Course Directors, Myrtle Beach, April 27 (2009).

Invited Talks:

1. “Selective Recognition of Cisplatin and Oxaliplatin GG Adducts by Cellular Proteins: The Importance of Differential Conformational Dynamics, Gordon Research Conference on DNA Damage, Mutagenesis and Cancer, Ventura CA, March 13 (2008).

2. “Differences in Conformation and Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts”, 10

th International Symposium on Platinum Coordination

Compounds in Cancer Chemotherapy, Verona Italy, December 1, 2007.

3. “Repair and Bypass of Platinum-DNA Adducts: From Structure to Function”, University of Kentucky, April 4, 2005.

4. “Protein Interactions with Platinum-DNA Adducts: From Structure to Function”, ”, 9th

International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, New York, October 9 (2003)

5. “Translesion Synthesis Past Pt-GG Adducts – How Useful Are the In Vitro Data Anyway?”, NIH, July 14, 2003.

6. “Translesion DNA Polymerases and Replicative Bypass of Platinum-DNA Adducts”, Wake Forest University, February 13, 2002.

7. “Factors Affecting the Mutational Specificity of Platinum-DNA Adducts”, International Conference on DNA Conformation, Modification and Recognition in Biomedicine”, Brno, Czech Republic, July 4, 2000.

8. “Specificity of Platinum DNA Adduct Repair”, 8th

International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, Oxford, England, March 29, 1999.

9. “Comparative Pharmacokinetics, Neurotoxicity, and Cytotoxicity of Oxaliplatin, Ormaplatin, and their Major Biotransformation Products”, 8

th International

Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, Oxford, England, March 29, 1999.

10. “Abortive Mismatch Repair: Evidence for Futile Cycling Opposite Platinum-DNA Adducts”. Wright State University, February 13, 1998

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11. “Platinum Complexes with the Diaminocyclohexane Carrier Ligand:Interactions with DNA and Effects of Resistance”, University of Maryland Cancer Center, Baltimore MD, December 3, 1996

12. “Platinum Complexes with the Diaminocyclohexane Carrier Ligand: Biotransformations, Neurotoxicity and Relationship to Mechanisms of Cisplatin Resistance”, Sanofi Research Division, Malvern PA, September 9, 1996

13. “Replicative Bypass of Platinum Adducts - The Trojan Horse Hypothesis”, Curriculum in Genetics and Molecular Biology, UNC, December 8, 1995

14. “The Metabolism and Neurotoxicity of Platinum Compounds with Diaminocyclohexane Carrier Ligands”, Regeneron Pharmaceuticals, Inc., July 21, 1995.

15. "DNA Repair and the Carrier Ligand Specificity of Platinum Resistance", Seventh International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, March 3, 1995.

16. "Mechanisms of Resistance to Platinum Anti-Cancer Agents", Department of Pharmacology, UNC, October 29, 1991

17. "Mechanisms of Resistance to Platinum Anti-Cancer Drugs", Carcinogenesis Seminar, UNC, October 7, 1991.

18. "Metabolism and Mechanism of Action of Ormaplatin", Division of Experimental Therapeutics, Duke Comprehensive Cancer Center, July, 1991.

19. "Carrier Ligand Effects in Platinum-Resistant Cell Lines", Sixth International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, January, 1991.

TEACHING RECORD: Course Director Medical Biochemistry 1975-1995 and 2000-2004 Molecules to Cells 2005 – present

Duties include evaluating and revising course content, integrating the course material with other basic science and clinical courses, developing new small group and integrative exercises, attending lectures given by course faculty. Time commitment is 5-15 hours/week

Lecture:

Molecules to Cells 19.5 hrs. Dental Biochemistry 8 hrs. Laboratory (Case Conferences and Problem-Based Cases): Molecules to Cells 16.5 hrs. Clinical Applications 2 hrs. Lab or research Teaching (Advisor): Graduate Students: Undergraduate Honors Students:

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Graduate Supervision, Committees: Thesis Committees Recipients of Graduate Degrees Trained Under My Direction: S. Ramachandran, PhD. Thesis completed in 2010 at the University of North Carolina at

Chapel Hill, entitled “Recognition of Platinum-DNA Adducts by HMG-Box Proteins” Irene Baskerville-Abraham, PhD. Thesis completed at the University of North Carolina at

Chapel Hill, entitled “Molecular Dosimetry of 1,2 Guanine-Guanine Intrastrand Cross Links of Cisplatin by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry”

P. Gong. MS. Thesis completed in 2006 at the University of North Carolina at Chapel

Hill, entitled “Modeling Conformational Dynamics of Cisplatin and Oxaliplatin Adducts with DNA”

E. Bassett, Research Scientist, Geron Pharmaceuticals. PhD. Thesis completed in 2004 at

the University of North Carolina at Chapel Hill, entitled “The Role of Translesion Synthesis in the Mutagenicity of Platinum Anticancer Agents”

F.R. Luo, Senior Research Investigator, Bristol Meyers Squibb. Ph.D. Thesis completed

in 1998 at the University of North Carolina at Chapel Hill, entitled “Relationship of Biotransformations and Pharmacokinetics with the Neurotoxicity and Efficacy of Oxaliplatin, A Potential Third Generation Anti-Cancer Drug”

E.L. Mamenta. Thesis complete in 1996 at the University of North Carolina at Chapel

Hill, entitled “The Effect of DNA Adducts on Replication in Cisplatin-Resistant Human Ovarian Carcinoma Cells”

D. Charles Thompson, Center for Drug Evaluation and Research, FDA, Thesis complete in 1995 at the University of North Carolina at Chapel Hill, entitled "Biotransformations of Ormaplatin in the Fischer 344 Rat."

Gregory R. Gibbons, Physician in private practice. Ph.D. Thesis completed in 1991 at

the University of North Carolina at Chapel Hill, entitled "Characterization of the Carrier Ligand Specific Resistance of L1210 Murine Leukemia Cells to Platinum Chemotherapeutic Agents."

Patrick F. Carfagna. MS. Thesis completed in 1989 at the University of North Carolina at

Chapel Hill, entitled “Effect of Chemoprotectors on the Toxicity and Biotransformation Products of Tetraplatin in the Fischer 344 Rat”

Stanley K. Mauldin, Senior Staff Fellow, Lankenau Medical Research Center,

Wynnewood, PA. Ph.D. Thesis completed in 1986 at the University of North Carolina at Chapel Hill, entitled "Studies on the Biotransformation of Two Second Generation Platinum Antitumor Drugs."

Steven H. Reynolds, Branch Chief, Laboratory of Toxicology and Molecular Biology,

NIOSH, Morganton, WV. Ph.D. Thesis completed in 1981 at the University of North

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Carolina at Chapel Hill, entitled "Stable RNA Synthesis in a Mutant Strain of Escherichia coli."

Jean Shearin Harris, Research Associate, Department of Medicine, Duke University

School of Medicine, Durham, NC. Ph.D. Thesis completed in 1976 at the University of North Carolina at Chapel Hill, entitled "Characterization of an E. coli Mutant Temperature Sensitive for rRNA Synthesis."

Undergraduate Honors Theses Completed Under My Direction Ruben Kuruvilla, “Molecular Dynamics Simulations of the Transcription Factor hSRY

with DNA Templates Containing Cisplatin and Oxaliplatin Adducts”, 2004. Mihir Faldu, “Molecular Dynamic Simulations of Pol-DNA Complexes Containing

Cisplatin and Oxaliplatin Adducts”, 2004. Anoop Patel, “Anti-Cancer Drugs and Their Effects on DNA Structure and Replication”,

2001. Kristen Tropea, “In Vitro Replication Studies with DNA Polymerase Beta”, 2001. Matt Warren, “Circumvention of Cisplatin Resistance by Ammine, 2-

Methylpyridinedichloroplatinum (II) (ZD0473)”, 2001. Other Supervision (Current Postdoctoral Research Associates) Postdoctoral Research Associates Trained Under My Direction:

Dr. Wimal Pathmasiri, 2007-2008 Dr. Debadeep Bhattacharrya, 2004-2007, Senior Staff Scientist, Oxford Instruments, Boston MA Dr. Yibing Wu, 2002-2004, Senior Staff Scientist in the laboratory of Tom Szyperski at the University of Buffalo

Dr. Padmanova Pradhan, 2001-2002, Director of NMR Facility, NYCU Dr. Jennifer Holmes, 1997 Dr. Dean Delmastro, 1993-1995, Director of Hematology and Oncology, Sacred Heart

Hospital, Marshfield Clinic Dr. Leslie DeMars, 1992-1993, Associate Professor, Division of Gynecological

Oncology, Department of Obstetrics and Gynecology, Eastern Virginia Medical School Dr. Wendelyn Schmidt, 1989-1992, IND Reviewer, Division of Oncology and

Pulmonary, Food and Drug Administration. Dr. David Thomas, 1988, Associate Professor, Department of Biochemistry, University

of Kentucky.

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Dr. Jim Page, 1984-1988, currently Research Associate Professor, Thrombosis Research

Center, Temple University. Dr. Intisar Husain 1984-1986, currently Senior Scientist, Department of Chemotherapy,

Glaxo Incorporated. Dr. Nabil S. Hanna 1975-1976, currently at Univesite Laval, Quebec, Canada. GRANTS FUNDED DURING LAST 10 YEARS: Active Support: Past Support (Last 10 Years): National Institutes of Health: "Error-Prone Replicative Bypass of Platinum Adducts", 4/1/04-

3/31/09; $225,000 direct costs/year. Principal Investigator, 30% Time and Effort, changed to Co-Investigator, 10% Time and Effort.

Sanofi-Synthelabo Inc.: “The Possible Role of TCF-4 and TCF-1 in Determining the Efficacy of

Oxaliplatin in Colon Cancer”, 01/01/05-12/31/05; $68,493 direct costs/year. Principal Investigator, 10% Time and Effort

MGI Pharma: “Identification and Quantification of Irofulven DNA Adducts”, 12/15/04-12/31/05; $63,248 direct cost/year, Principal Investigator, 10% Time and Effort National Institutes of Health: “Binding Network of Pol Eta in DNA Damage Responses”

09/01/02-08/31/04, $150,000 direct costs/year, Co-Investigator, 10% Time and Effort. National Institutes of Health: "Error-Prone Replicative Bypass of Platinum Adducts", 7/1/00-

6/30/04; $200,000 direct costs/year. Principal Investigator, 30% Time and Effort. AstraZeneca Pharmaceuticals: “Effects of ZD0473 Adducts on DNA Repair and Tolerance

Mechanisms”, 06/01/00 – 05/30/01, $67,000 direct costs/year; Principal Investigator, 10% Time and Effort (Terminated 12/31/01 because Astra-Zeneca decided against further development of ZD0473)

Sanofi-Synthelabo Pharmaceuticals: “Mechanisms of Tirapazamine Interactions with Platinum

Anticancer Agents”, 1/1/98 - 12/31/00, $ 57,000 direct costs/year; Principal Investigator, 10% Time and Effort

Aronex Pharmaceuticals: “Activation, Biotransformations, and Mechanism of Activation of a

Lipophilic Cisplatin Analog Entrapped in Liposomes”, 01/01/00 – 12/31/00, $62,715 direct costs; Principal Investigator, 10% Time and Effort

Sanofi-Synthelabo Pharmaceuticals: “Characterization of Repair Differences for Oxaliplatin and

Cisplatin Adducts”, 1/1/98 – 7/1/00; $ 45,000 direct costs/year; Principal Investigator, 20% Time and Effort

Sanofi-Winthrop Pharmaceuticals: “Cytotoxicity and Mechanisms of Action for Oxaliplatin and

Oxaliplatin Plus Fluorouracil”, 1/1/97 – 12/31/97; $ 60,900 direct costs/year; Principal Investigator, 20% Time and Effort

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National Institutes of Health: "Biotransformation Studies with Ormaplatin", 7/1/95-6/30/99; $158,000 direct costs/year. Principal Investigator, 25% Time and Effort.

PROFESSIONAL SERVICE: UNC Committees: Department of Biochemistry and Biophysics Teaching Excellence and Innovation Committee, Chair, 2006-present School of Medicine:

First Year Curriculum Committee, 2001-2009

Co-Chair, First Year Curriculum Committee, 2002-2009

Curriculum Management and Policy Committee, 2002-2009

Student Promotions Committee, 2006-2009

Academy of Educators, 2007-present

University

Academy of Educators

Chair, Teaching Awards Committee, 2007-present

REFLECTIVE STATEMENT (December 12, 2006):

My father and grandfather were chemists, so I always knew that I wanted a career in

science. My father worked in industry, but I chose an academic career because I wanted the

freedom to pursue my own ideas. What I did not anticipate is how much I would love teaching.

While striving for excellence in both teaching and research can be overwhelming at times, it is

the opportunity to switch back and forth between teaching and research that has kept me engaged

and excited over the years. The enthusiasm and love of learning that the students display

constantly reminds me of why I got into science in the first place. I enjoy all phases of teaching.

In the lecture hall I enjoy the challenge of making the information understandable and interesting

to the students, and assuring that it is relevant to their clinical careers. In small group teaching I

enjoy the challenge of asking just the right questions to help students connect the facts that they

have learned in such a way that they can apply them to solving a clinical problem, for it is their

clinical problem-solving skills that are ultimately much more important than all of the facts that

we teach them. With the graduate and undergraduate students in my lab, I most enjoy the

opportunity to be a mentor for them. It is often more important to tell what they are doing right

than what they are doing wrong to help them develop the confidence that they will need for a

successful research career.

I often reflect on the fact that major research institutions like UNC recruit their basic

science faculty almost entirely on the basis of their research accomplishments, rather than their

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ability to teach. Because we have not had any training in education, most of us arrive on campus

unqualified to teach at even a grade school level in the public school system. Those of us who go

on to become good teachers do so because we love it. Of course, I also credit the many excellent

teaching seminars offered by the Office of Educational Development and my participation in the

Teaching Scholars Program with helping me improve my teaching skills. While my teaching

skills were mediocre at best when I arrived on campus, I have consistently received excellent

ratings for my teaching from students in the medical and dental biochemistry courses over the

past 10-15 years. In addition, the Whitehead Student Medical Society recognized me with the

Freshman Basic Science Teaching Award for the 2002-2003 and 2004-2005 academic years and I

have been named a Medical Alumni Distinguished Teaching Professor.

More recently, I have also had the opportunity to become involved in curriculum

management and development. In 2002 I was appointed Co-Chair of the First Year Curriculum

Committee and a member of the Curriculum Management and Policy Committee for the medical

school. At that time there were a number of first year course directors who were interested in

developing a more innovative, clinically relevant curriculum, but were frustrated by the rigid,

departmental nature of our curriculum. In 2003 I co-chaired a task force that transformed the

first year medical curriculum from a traditional discipline-based curriculum to a highly

integrated, more clinically relevant curriculum. Subsequently I have been involved in the

revision of the year 3-4 curriculum. It is an exciting time to be involved with the medical school

curriculum because we have developed a flexible governance structure that encourages

continuous quality improvement. I look forward to leading the development of this curriculum in

the future, while continuing to be directly involved in my first love, namely teaching.

UNC has been an ideal place for me to build my scientific career because of the resources

available and the collaborative spirit of the faculty here. My research over the past 25 years has

focused on platinum anticancer agents. As is often the case, this research started out as a

collaboration with a colleague in the School of Pharmacy who was interested in having me

evaluate some platinum complexes that they had prepared. However, once I realized how little

was known about how these compounds actually worked, I obtained NIH funding and embarked

on a detailed characterization of the action mechanism of platinum anticancer agents – work that

continues today. At the time my studies began two platinum compounds, cisplatin and

carboplatin, were widely used in cancer chemotherapy. These compounds were structurally

similar and had a virtually identical tumor range. There were also two structurally simular

compounds, oxaliplatin and ormaplatin, in clinical development that had very different toxicity

profiles and tumor range than cisplatin and carboplatin. These compounds were effective in

many cisplatin- and carboplatin- resistant tumors and cell lines, but almost nothing was known

about how these compounds evaded the resistance to other platinum compounds. I felt that a

better understanding of the mechanisms by which these compounds overcame cisplatin-resistance

could lead to the development of more effective platinum anticancer agents and assays that

would allow an oncologist to predict which patients would respond best to each type of platinum

anticancer agent.

My laboratory has studied mechanisms of platinum resistance in tumor cell lines and has

determined which of those mechanisms discriminate between the different classes of platinum

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anticancer agents. We also developed a method for separating, identifying and quantifying the

metabolites of oxaliplatin and ormaplatin and have studied the metabolism of these compounds

in both cell culture and whole animals. We were able to show which metabolites were

responsible for the toxicity and efficacy of these compounds and were eventually able to study

the metabolism of these compounds in a human clinical trial. The latter study was performed in

collaboration with colleagues in the Department of Medicine and School of Pharmacy.

Of course, one of the keys to a long research career is the ability to shift one’s research

focus as old ideas go out of fashion and new ideas emerge. About 8 years ago it became apparent

that research support for understanding the action mechanisms of platinum anticancer agents was

beginning to wane. At about the same time a new class of translesion DNA polymerases was

discovered that had the ability to bypass bulky DNA adducts during DNA replication. Starting

with industry support, we showed that several of these DNA polymerases were capable of

bypassing platinum adducts in DNA. I then obtained NIH funding and we showed that these

polymerases bypassed ciplatin- and oxaliplatin-DNA adducts with different efficiency and

fidelity and that, as a result, oxaliplatin was far less mutagenic than cisplatin. More recently, I

decided that to truly understand the mechanism of this discrimination and to design more

effective platinum anticancer agents, we needed to know how these platinum compounds

affected the structure of DNA when they bound to it and how these platinum-DNA adducts

interacted with the DNA polymerases and other cellular proteins. I put together a collaborative

NIH-funded project with other members of the Biochemistry and Biophysics Department in

which we are using a combination of enzyme kinetics, NMR structural determinations and

computer modeling to answer these questions.

In my career to date I have published 92 articles and 12 reviews in peer-reviewed

scientific journals. I have been asked to be a keynote speaker at the last 3 international

conferences on platinum anticancer agents. One of the compounds that I have characterized

(oxaliplatin) was approved by the FDA 3 years ago and is now very widely used because of its

effectiveness in treating metastatic colon cancer and other cisplatin-unresponsive tumors. I

would like to think that my characterization of the metabolism, action mechanism, toxicity and

efficacy of this compound played an important role in its approval by the FDA. I remain as

excited about my research today as I was the day that I started at UNC.