Curriculum Vitae Thomas J. Urban, Pharm.D., Ph.D. 120 Mason Farm Road, Genetic Medicine Building Room 1014 Chapel Hill, NC 27599-­‐7361 (919)966-­‐0512 thomas.urban@unc.edu Positions Held Aug 2014-­‐Present March 2010-­‐July 2014: June 2007-­‐Feb. 2010: Assistant Professor University of North Carolina at Chapel Hill Division of Pharmacotherapy and Experimental Therapeutics Center for Pharmacogenomics and Individualized Therapy UNC Eshelman School of Pharmacy UNC Hamner Institute for Drug Safety Sciences Assistant Professor in Medicine Duke University Medical Center, Durham, NC Center for Human Genome Variation Department of Medicine, Section of Medical Genetics Postdoctoral Associate Duke University, Durham, NC Center for Population Genetics and Pharmacogenomics, Institute for Genome Sciences & Policy Education Institution Date Degree Pharmacogenomics University of California San Francisco 2007 Ph.D. Chemistry/Pharmacy University of North Carolina Chapel Hill 2001 Pharm.D. Fellowships Epilepsy Foundation Postdoctoral Research Fellowship, 2009 PhRMA Foundation Predoctoral Fellowship in Pharmaceutics, 2004-­‐2006 NIH Training Grant in Pharmacology, 2001-­‐2004 Honors Long Award for Excellence in Teaching, UCSF, 2001-­‐2002 William H. Brown Memorial Scholarship, 2000-­‐2001 Wal-­‐Mart Pharmacy Scholarship, 1999-­‐2000 University of North Carolina Trademark Scholar, 1994 -­‐ 2000 Professional Organizations HepNet (Viral Hepatitis Network in West Africa), Founding Member 2013-­‐present North Carolina Pharmacogenetics Partnership (NCPGX), Executive Member 2008-­‐2010 RTP Drug Metabolism Discussion Group (RTP-­‐DMDG), Executive Member 2007-­‐2009 American Association for the Study of Liver Diseases American Society of Human Genetics American Society for Clinical Pharmacology and Therapeutics Rho Chi Society, Alpha Lambda Chapter Thomas J. Urban
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Research Experience and Interests My research is primarily focused on applying the most contemporary genetics and genomics techniques to identify DNA sequence variants that are associated with variable drug responses. In contrast to the results of many genome-­‐wide studies of common human diseases, pharmacogenetic studies in the past few years have yielded a significant number of common, high-­‐impact variants influencing a variety of different drug response traits. I, along with colleagues in the Duke Center for Human Genome Variation and our clinical collaborators, have been involved in a number of such discoveries, including the association of IL28B variation in response to interferon-­‐based hepatitis C treatment, the role of functional variation in the ITPA gene in risk for ribavirin-­‐induced hemolytic anemia, and the influence of both Class I and Class II HLA alleles in risk for drug-­‐induced liver injury. My current work involves the use of whole-­‐exome and whole-­‐genome sequencing to identify the genetic causes of rare drug toxicities such as drug-­‐induced arrhythmias and drug-­‐induced liver injury, as well as therapeutic efficacy of a variety of drugs across different therapeutic classes. Further, I am interested in understanding the mechanism(s) and biological impact of genetic variants associated with drug responses, and have been active in functional studies of IL28B and ITPA variants and their effects in in vitro and ex vivo studies using human cells or tissue. My goals in the near term are to continue to work toward discovery of novel genetic predictors of drug response, and to use this to learn about the biology underlying variability in drug response. Teaching Experience Lead instructor and course coordinator for PHAR370S: Pharmacogenomics and Personalized Medicine, an undergraduate course at Duke which teaches basic principles of pharmacology, genetics and statistics and how these are applied to study the genetic basis of variation in drug response. (Spring semester, 2010-­‐2014) Co-­‐instructor for MGM/UPG232: Human Genetics, a graduate-­‐level course at Duke surveying human genetics through didactic teaching and literature discussion. I led a module focused on pharmacogenomics, cancer genomics and experimental molecular therapeutics. (Spring semester, 2012-­‐2014) Guest lecturer for PHCY412: Principles of Pharmacodynamics at UNC Eshelman School of Pharmacy, giving two lectures per year on the topic of pharmacogenetics/pharmacogenomics. (Spring semester, 2010-­‐present) Guest lecturer for DPET832: Introduction to Applied Pharmacogenomics at UNC Eshelman School of Pharmacy, giving two lectures per year on the topics of liver-­‐related pharmacogenomics and genetics of hypersensitivity reactions. (Fall semester, 2012-­‐present) Guest lecturer for DPET838: Methods in Pharmacogenomics at UNC Eshelman School of Pharmacy, giving two hours of lecture on the topic of genome-­‐wide association studies, methods and interpretation (Spring semester, 2015-­‐present) Publications 1. Towards predicting drug-­‐induced liver injury (DILI): parallel computational approaches to identify MRP4 and BSEP inhibitors. Matthew A. Welch, Kathleen Köck, Thomas J. Urban, Kim L.R. Brouwer, Peter W. Swaan. 2015 (under review). 2. IFNL3 mRNA structure is transformed by a functional non-­‐coding polymorphism associated with hepatitis C virus clearance. Yi-­‐Fan Lu, David M. Mauger, David B. Goldstein, Thomas J. Urban, Kevin M. Weeks, Shelton S. Bradrick. 2015 (under review). Thomas J. Urban
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3. Prevalence of genetic variants of keratins 8 and 18 in patients with drug-­‐induced liver injury. Valentyn Usachov, Thomas J. Urban, Robert J. Fontana, Annika Gross, Sapna Iyer, M. Bishr Omary, Pavel Strnad, on behalf of the Drug-­‐Induced Liver Injury Network. 2015 (under review). 4. Clinical application of whole genome sequencing in patients with primary immunodeficiency. Talal Mousallem, Thomas J. Urban, Keisha M. McSweeney, Sarah E. Kleinstein, Mingfu Zhu, Mehdi Adeli, Roberta E. Parrott, Joseph L. Roberts, Brian Krueger, Rebecca H. Buckley, David B. Goldstein. J Allergy Clin Immunol 2015 (in press). 5. Population pharmacokinetic modeling of plasma and intracellular ribavirin concentrations in patients with chronic hepatitis C virus. Liviawati Wu, Joseph Rower, James Burton, Peter Anderson, Kyle Hammond, Fafa Baouchi-­‐Mokrane, Gregory Everson, Thomas Urban, David D'Argenio, Jennifer Kiser. Antimicrobial Agents and Chemotherapy 2015 (in press). 6. Interferon-­‐lambda-­‐4 is a cell-­‐autonomous type III interferon associated with pre-­‐treatment hepatitis C virus burden. Yi-­‐Fan Lu, David B. Goldstein, Thomas J. Urban, Shelton S. Bradrick. Virology 476C:334-­‐40, 2015. 7. Genetic basis of drug-­‐induced liver injury: present and future. Thomas J. Urban, Ann K. Daly, Guruprasad P. Aithal. Sem Liv Dis 34(2):123-­‐33, 2014. 8. Sensitivity to hepatotoxicity due to epigallocatechin gallate is affected by genetic background in diversity outbred mice. Rachel J. Church, Daniel M. Gatti, Thomas J. Urban, Nanye Long, Xi Yang, Qiang Shi, J. Scott Eaddy, Merrie Mosedale, Shawn Ballard, Gary A. Churchill, Victor Navarro, Paul B. Watkins, David W. Threadgill, Alison H. Harrill. Food Chem Toxicol 76C:19-­‐26, 2014. 9. A nonsense mutation in IKBKB causes combined immunodeficiency. Talal Mousallem, Jialong Yang, Thomas J. Urban, Hongxia Wang, Mehdi Adeli, Roberta E. Parrott, Joseph L. Roberts, David B. Goldstein, Rebecca H. Buckley, Xiao-­‐Ping Zhong. Blood 124(13):2046-­‐50, 2014. 10. Genome-­‐wide association study to characterize serum bilirubin elevations in patients with HCV treated with GS-­‐9256, an HCV NS3 serine protease inhibitor. David Nelson, Eric M. Yoshida, Matthew S. Paulson, Paul N. Hengen, Dongliang Ge, Bittoo Kanwar, John McNally, Phil S. Pang, G. Mani Subramanian, John G. McHutchison, Petr Urbanek, Eric Lawitz, Thomas J. Urban†. Antivir Ther, 19(7):679-­‐86, 2014. 11. Pharmacogenetics at 50: genomic personalization comes of age. Thomas J. Urban†, David B. Goldstein. Science Translational Medicine 6(220):220ps1, 2013. 12. Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy. Paul J. Clark, Alessio Aghemo, Elisabetta Degasperi, Enrico Galmozzi, Thomas J. Urban, David M. Vock, Keyur Patel, Alexander J. Thompson, Maria Grazia Rumi, Roberta D'Ambrosio, Andrew J. Muir, Massimo Colombo. J Viral Hepat 20(12):858-­‐66, 2013. 13. Risk factors for development of cholestatic drug-­‐induced liver injury: inhibition of hepatic basolateral bile acid transporters MRP3 and MRP4. Kathleen Köck, Brian Ferslew, Ida Netterberg, Kyunghee Yang, Thomas J. Urban, Peter W. Swaan, Paul W. Stewart, Kim L.R. Brouwer. Drug Metab Dispos 42(4):665-­‐74, 2013. 14. Kinetic differences in the induction of interferon stimulated genes by interferon-­‐α and IL28B are altered by infection with Hepatitis C virus. Nikolaus Jilg, Wenyu Lin, Jian Hong, Esperance A. Schaefer, David Wolski, James Meixong, Kaku Goto, Cynthia Brisac, Pattranuch Chusri, Dhalene N. Fusco, Stephanie Chevaliez, Jay Luther, Kattareeya Kumthip, Thomas J. Urban, Lee F. Peng, Georg M. Lauer, Raymond T. Chung. Hepatology 59(4):1250-­‐61, 2013. 15. Understanding human variation in infectious disease susceptibility through clinical and cellular GWAS. Dennis C. Ko, Thomas J. Urban. PLoS Pathogens 9(8):e1003424, 2013. 16. Whole-­‐genome sequencing in pharmacogenetics. Thomas J. Urban†, Pharmacogenomics 14(4):345-­‐8, 2013. 17. Impact of the interaction between 3’-­‐UTR SNPs and microRNA on the expression of human xenobiotic metabolism enzyme (XME) genes. Rongrong Wei, Fan Yang, Thomas J. Urban, Lang Li, Naga Chalasani, David A. Flockhart, Wanqing Liu. Front Genet 3:248, 2012. Thomas J. Urban
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18. Prioritizing genetic variants for causality on the basis of preferential linkage disequilibrium. Qianqian Zhu, Dongliang Ge, Erin L. Heinzen, Samuel P. Dickson, Thomas J. Urban, Mingfu Zhu, Jessica M. Maia, Min He, Qian Zhao, Kevin V. Shianna, David B. Goldstein. Am J Hum Genet 91(3):422-­‐34, 2012. 19. Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs. Thomas J. Urban, Yufeng Shen, Andrew Stolz, Naga Chalasani, Robert J. Fontana, James Rochon, Dongliang Ge, Kevin V. Shianna, Ann K. Daly, M. Isabel Lucena, Matthew R. Nelson, Mariam Molokhia, Guruprasad Aithal, Aris Floratos, Itsik Pe’er, Jose Serrano, Herbert Bonkovsky, Timothy J. Davern, William M. Lee, Victor J. Navarro, Jayant A. Talwalkar, David B. Goldstein, Paul B. Watkins, on behalf of the Drug Induced Liver Injury Network and the International Serious Adverse Events Consortium. Pharmacogenet Genomics 22(11):784-­‐795, 2012. 20. The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic hepatitis C infection. Paul J. Clark, Alexander J. Thompson, Qianqian Zhu, David M. Vock, Mingfu Zhu, Keyur Patel, Stephen A. Harrison, Susanna Naggie, Dongliang Ge, Hans L. Tillmann, Thomas J. Urban, Kevin Shianna, Jacques Fellay, Zachary Goodman, Stephanie Noviello, Lisa D. Pedicone, Nezam Afdhal, Mark Sulkowski, Janice K. Albrecht, David B. Goldstein, John G. McHutchison, Andrew J. Muir. Dig Dis Sci 57(8):2213-­‐21, 2012. 21. Genetic basis of susceptibility to DILI: what have we learned and where do we go from here? Thomas J. Urban†, David B. Goldstein, Paul B. Watkins. Pharmacogenomics 13(7):735-­‐8, 2012. 22. Introduction to the genetics and biology of IL28B. Thomas J. Urban, Michael R. Charlton, David B. Goldstein. Hepatology 56(1):361-­‐6, 2012. 23. Interleukin 28B polymorphisms are the only common genetic variants associated with low-­‐
density lipoprotein cholesterol (LDL-­‐C) in genotype-­‐1 chronic hepatitis C and determine the association between LDL-­‐C and treatment response. Paul J. Clark, Alexander J. Thompson, Mingfu Zhu, David M. Vock, Qianqian Zhu, Dongliang Ge, Keyur Patel, Stephen A. Harrison, Thomas J. Urban, Susanna Naggie, Jacques Fellay, Hans L. Tillmann, Kevin Shianna, Stephanie Noviello, Lisa D. Pedicone, Rafael Esteban, Paul Kwo, Mark S. Sulkowski, Nezam Afdhal, Janice K. Albrecht, David B. Goldstein, John G. McHutchison, Andrew J. Muir, IDEAL Investigators. J Viral Hepat 19(5):332-­‐40, 2012. 24. Genome-­‐wide mapping for clinically relevant predictors of lamotrigine-­‐ and phenytoin-­‐induced hypersensitivity reactions. Mark McCormack, Thomas J. Urban, Kevin V. Shianna, Nicole Walley, Massimo Pandolfo, Chantal Depondt, Elijah Chaila, Gerard D. O’Conner, Dalia Kasperavičiūtė, Rodney A. Radtke, Erin L. Heinzen, Sanjay M. Sisodiya, Norman Delanty, Gianpiero L. Cavalleri. Pharmacogenomics 13(4):399-­‐405, 2012. 25. Copy number variation of KIR genes influences HIV-­‐1 control. Kimberly Pelak, Anna C. Need, Jacques Fellay, Kevin V. Shianna, Sheng Feng, Thomas J. Urban, Dongliang Ge, Andrea DeLuca, Javier Martinez-­‐Picado, Steven M. Wolinsky, Jeremy J. Martinson, Beth D. Jamieson, Jay H. Bream, Maureen P. Martin, Persephone Borrow, Norman L. Letvin, Andrew J. McMichael, Barton F. Haynes, Amalio Telenti, Mary Carrington, David B. Goldstein, Galit Alter, on behalf of NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). PLoS Biol 9(11):e1001208, 2012. 26. Genetic and environmental correlates of topiramate-­‐induced cognitive impairment. Elizabeth T. Cirulli, Thomas J. Urban, Susan E. Marino, Kristen N. Linney, Angela K. Birnbaum, Chantal Depondt, Deborah K. Attix, Rodney A. Radtke, David B. Goldstein. Epilepsia 53(1):e5-­‐e8, 2012. 27. Genome-­‐wide association study of interferon-­‐related cytopenia in chronic hepatitis C patients. Alexander J. Thompson, Paul J. Clark, Abanish Singh, Dongliang Ge, Jacques Fellay, Mingfu Zhu, Qianqian Zhu, Thomas J. Urban, Keyur Patel, Hans L. Tillmann, Susanna Naggie, Nezam H. Afdhal, Ira M. Jacobson, Rafael Esteban, Fred Poordad, Eric J. Lawitz, Jonathan McCone, Mitchell L. Shiffman, Greg W. Galler, John W. King, Paul Y. Kwo, Kevin V. Shianna, Stephanie Noviello, Lisa D. Pedicone, Clifford A. Brass, Janice K. Albrecht, Mark S. Sulkowski, David B. Goldstein, John G. McHutchison, Andrew J. Muir. J Hepatol 56(2):313-­‐9, 2012.
Thomas J. Urban
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28. Susceptibility to amoxicillin-­‐clavulanate-­‐induced liver injury is influenced by multiple HLA class I and class II alleles. M. Isabel Lucena, Mariam Molokhia, Yufeng Shen, Thomas J. Urban, Guruprasad P. Aithal, Raul J. Andrade, Christopher P. Day, Francisco Ruiz-­‐Cabello, Peter T. Donaldson, Camilla Stephens, Munir Pirmohamed, Manuel Romero-­‐Gomez, Jose Maria Navarro, Robert J. Fontana, Michael Miller, Max Groome, Emmanuelle Bondon-­‐Guitton, Anita Conforti, Bruno H.C. Stricker, Alfonso Carvajal, Luisa Ibanez, Qun-­‐Ying Yue, Michel Eichelbaum, Aris Floratos, Itsik Pe’er, Mark J. Daly, David B. Goldstein, John F. Dillon, Matthew R. Nelson, Paul B. Watkins, Ann K. Daly, Spanish DILI Registry, EUDRAGENE, DILIN, DILIGEN, and International SAEC. Gastroenterology 141(1):338-­‐47, 2011. 29. IL28B genotype effects during early treatment with peginterferon and ribavirin in difficult-­‐to-­‐
treat hepatitis C virus infection. John Scott, Sarah Holte, Thomas Urban, Caitlin Burgess, Erica Coppel, Chia Wang, Larry Correy, John McHutchison, David Goldstein. J Infect Dis 204(3):419-­‐25, 2011. 30. ITP protects against ribavirin-­‐induced anemia by restoring adenylosuccinate synthase function in the biosynthesis of ATP. Yuki Hitomi, Elizabeth T. Cirulli, Jacques Fellay, John G. McHutchison, Alexander J. Thompson, Curtis E. Gumbs, Kevin V. Shianna, Thomas J. Urban, David B. Goldstein. Gastroenterology 140(4):1314-­‐21, 2011. 31. IL28B genotype is associated with differential expression of intrahepatic interferon-­‐stimulated genes in chronic hepatitis C patients. Thomas J. Urban*, Alexander J. Thompson*, Shelton S. Bradrick*, Jacques Fellay, Detlef Schuppan, Kenneth D. Cronin, Linda Hong, Alexander McKenzie, Keyur Patel, Kevin V. Shianna, John G. McHutchison, David B. Goldstein, Nezam Afdhal. Hepatology 52(6):1888-­‐96, 2010. 32. Interleukin-­‐28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Alexander J. Thompson, Andrew J. Muir, Mark S. Sulkowski, Dongliang Ge, Jacques Fellay, Kevin V. Shianna, Thomas Urban, Nezam H. Afdhal, Ira M. Jacobson, Rafael Esteban, Fred Poordad, Eric J. Lawitz, Jonathan McCone, Mitchell L. Shiffman, Greg W. Galler, William M. Lee, Robert Reindollar, John W. King, Paul Y. Kwo, Reem H. Ghalib, Bradley Freilich, Lisa M. Nyberg, Stefan Zeuzem, Thierry Poynard, David M. Vock, Karen S. Pieper, Keyur Patel, Hans L. Tillmann, Stephanie Noviello, Kenneth Koury, Lisa D. Pedicone, Clifford A. Brass, Janice K. Albrecht, David B. Goldstein, John G. McHutchison. Gastroenterology 139(1):120-­‐9, 2010. 33. Variants in the ITPA Gene Protect Against Ribavirin-­‐Induced Hemolytic Anemia and Decrease the Need for Ribavirin Dose Reduction. Alexander J. Thompson, Jacques Fellay, Keyur Patel, Hans L. Tillmann, Susanna Naggie, Dongliang Ge, Thomas J. Urban, Kevin V. Shianna, Andrew J. Muir, Michael W. Fried, Nezam H. Afdhal, David B. Goldstein, John G. McHutchison. Gastroenterology 139(4):1181-­‐9, 2010. 34. Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes. Erin L. Heinzen*, Rodney A. Radtke*, Thomas J. Urban*, Gianperro L. Cavalleri, Chantal Depondt, Anna C. Need, Nicole M. Walley, Paola Nicoletti, Dongliang Ge, Claudia B. Catarino, John S. Duncan, Dalia Kasperavičiūtė, Sarah K. Tate, Luis O. Caboclo, Josemir W. Sander, Lisa Clayton, Kristen N. Linney, Kevin V. Shianna, Curtis E. Gumbs, Jason Smith, Kenneth D. Cronin, Jessica M. Maia, Colin P. Doherty, Massimo Pandolfo, David Leppert, Lefkos T. Middleton, Rachel A. Gibson, Michael R. Johnson, Paul M. Matthews, David Hosford, Reetta Kälviäinen, Kai Eriksson, Anne-­‐
Mari Kantanen, Thomas Dorn, Jörg Hansen, Günter Krämer, Bernhard J. Steinhoff, Heinz-­‐Gregor Wieser, Dominik Zumsteg, Marcos Ortega, Nicholas W. Wood, Julie Huxley-­‐Jones, Mohamad Mikati, William B. Gallentine, Aatif M. Husain, Patrick G. Buckley, Ray L. Stallings, Mihai V. Podgoreanu, Norman Delanty, Sanjay M. Sisodiya, David B. Goldstein. Am J Hum Genet 86(5):707-­‐18, 2010. 35. ITPA gene variants protect against anemia in patients treated for chronic hepatitis C infection. Jacques Fellay, Alexander J. Thompson, Dongliang Ge, Curtis E. Gumbs, Thomas J. Urban, Kevin V. Shianna, Latasha D. Little, Ping Qiu, Arthur H. Bertelsen, Mark Watson, Amelia Warner, Thomas J. Urban
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Andrew J. Muir, Clifford Brass, Janice Albrecht, Mark Sulkowski, John G. McHutchison, David B. Goldstein. Nature 464(7287): 405-­‐408, 2010. Race, Ethnicity, Ancestry and Pharmacogenetics. Thomas J. Urban†. Mt Sinai J Med 77(2): 133-­‐
139, 2010. CYP2C9*1B Promoter Polymorphisms, in Linkage Disequilibrium with CYP2C19*2, Affect Phenytoin Auto-­‐induction of Clearance and Maintenance Dose. Amarjit S. Chaudhry*, Thomas J. Urban*, Jatinder K. Lamba, Angela K. Birnbaum, Rory P. Remmel, Murali Subramanian, Stephen Strom, Joyce H. You, Rinki Singh, Dalia Kasperaviciute, Claudia Catarino, Rodney A. Radtke, Sanjay M. Sisodiya, David B. Goldstein, Erin G. Schuetz. J Pharmacol Exper Ther 332(2): 599-­‐611, 2010. Common Genetic Variation and the Control of HIV-­‐1 in Humans. Jacques Fellay, Dongliang Ge, Kevin V. Shianna, Sara Colombo, Bruno Ledergerber, Elizabeth T. Cirulli, Thomas J. Urban, Kunlin Zhang, Curtis E. Gumbs, Jason P. Smith, Antonella Castagna, Alessandro Cozzi-­‐Lepri, Andrea DeLuca, Philippa Easterbrook, Huldrych F. Günthard, Simon Mallal, Cristina Mussini, Judith Dalmau, Javier Martinez-­‐Picado, José M. Miro, Niels Obel, Steven M. Wolinsky, Jeremy J. Martinson, Roger Detels, Joseph B. Margolick, Lisa P. Jacobson, Patrick Descombes, Stylianos E. Antonarakis, Jacques S. Beckmann, Stephen J. O’Brien, Norman L. Letvin, Andrew J. McMichael, Barton F. Haynes, Mary Carrington, Sheng Feng, Amalio Telenti, David B. Goldstein, for the NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). PLoS Genet 5(112):e1000791, 2009. CCL3L1 and HIV-­‐AIDS Susceptibility. Thomas J. Urban, Amy C. Weintrob, Jacques Fellay, Sara Colombo, Kevin V. Shianna, Curtis Gumbs, Margalida Rotger, Kimberly Pelak, Kristen K. Dang, Roger Detels, Jeremy J. Martinson, Stephen J. O’Brien, Norman L. Letvin, Andrew J. McMichael, Barton F. Haynes, Mary Carrington, Amalio Telenti, Nelson L. Michael, David B. Goldstein. Nat Med 15(10):1110-­‐1112, 2009. Genetic Variation in IL28B Predicts Hepatitis C Treatment-­‐Induced Viral Clearance. Dongliang Ge, Jacques Fellay, Alexander J. Thompson, Jason S. Simon, Kevin V. Shianna, Thomas J. Urban, Erin L. Heinzen, Ping Qiu, Arthur H. Bertelsen, Andrew J. Muir, Mark Sulkowski, John G. McHutchison, David B. Goldstein. Nature 461(7262): 399-­‐401, 2009. The Organic Cation Transporter, OCTN1, Expressed in the Human Heart, Potentiates Antagonism of the HERG Potassium Channel. Brian F. McBride, Tao Yang, Kai Liu, Thomas J. Urban, Kathleen M. Giacomini, Richard B. Kim, Dan M. Roden. J Cardiovasc Pharmacol 54(1):63-­‐71, 2009. Effect of Genetic Variation in the Organic Cation Transporter 2 on the Renal Elimination of Metformin. Ying Chen, Shuanglian Li, Chaline Brown, Stephen Cheatham, Richard A. Castro, Maya K. Leabman, Thomas J. Urban, Ligong Chen, Sook Wah Yee, Ji Ha Chio, Yong Huang, Claire M. Brett, Esteban G. Burchard, Kathleen M. Giacomini. Pharmacogenet Genomics 19(7): 497-­‐504, 2009. WGAViewer: Software for Genomic Annotation of Whole Genome Association Studies. Dongliang Ge, Kunlin Zhang, Anna C. Need, Olivier Martin, Jacques Fellay, Thomas J. Urban, Amalio Telenti, David B. Goldstein. Genome Res 18(4): 640-­‐3, 2008. Functional Genetic Variation in the Basal Promoter of the Organic Cation/Carnitine Transporters, OCTN1 (SLC22A4) and OCTN2 (SLC22A5). Harunobu Tahara, Sook Wah Yee, Thomas J. Urban, Stephanie Hesselson, Richard A. Castro, Michiko Kawamoto, Doug Stryke, Susan J. Johns, Thomas E. Ferrin, Pui-­‐Yan Kwok, Kathleen M. Giacomini. J Pharmacol Exper Ther 329(1): 262-­‐71, 2009. The Organic Anion Transporter 2 (SLC22A7) is a Facilitative Transporter of cGMP. Cheryl D. Cropp, Takafumi Komori, James E. Shima, Thomas J. Urban, Sook Wah Yee, Swati S. More, Kathleen M. Giacomini. Mol Pharmacol 73(4): 1151-­‐8, 2008. Effects of Genetic Variation in the Novel Organic Cation Transporter, OCTN1, on the Renal Clearance of Gabapentin. Thomas J. Urban, Chaline Brown, Richard A. Castro, Nina Shah, Rachel Mercer, Yong Huang, Claire M. Brett, Esteban G. Burchard, Kathleen M. Giacomini. Clin Pharmacol Ther 83(3): 416-­‐21, 2007. Functional Effects of Protein Sequence Polymorphisms in the Multispecific Organic Cation/Ergothioneine Transporter OCTN1 (SLC22A4). Thomas J. Urban, Chen Yang, Leah L. Lagpacan, Chaline Brown, Richard A. Castro, Travis R. Taylor, Conrad C. Huang, Doug Stryke, Susan J. Thomas J. Urban
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Johns, Michiko Kawamoto, Elaine J. Carlson, Thomas E. Ferrin, Esteban G. Burchard, Kathleen M. Giacomini. Pharmacogenet Genomics 17(9): 773-­‐82, 2007. Functional Genetic Variation in the High-­‐Affinity Carnitine Transporter OCTN2 (SLC22A5). Thomas J. Urban, Renata C. Gallagher, Leah L. Lagpacan, Chaline Brown, Richard A. Castro, Claire M. Brett, Travis R. Taylor, Conrad C. Huang, Susan J. Johns, Michiko Kawamoto, Douglas Stryke, Elaine J. Carlson, Thomas E. Ferrin, Esteban G. Burchard, Seymour Packman, Kathleen M. Giacomini. Mol Pharmacol 70(5) 1602-­‐11, 2006. PharmGKB Submission Update: V. PMT Submissions of Genetic Variation in SLC22 Family Transporters. Yan Shu, Thomas J. Urban, Maya K. Leabman, Tomoe Fujita, Andrew R. Erdman, Leah L. Lagpacan, Chaline Brown, Richard A. Castro, Conrad C. Huang, Douglas Stryke, Michiko Kawamoto, Susan J. Johns, Travis R. Taylor, Wendy Chan, Melanie de la Cruz, Elaine J. Carlson, Thomas E. Ferrin, Claire M. Brett, Esteban G. Burchard, Ira Herskowitz, Deanna L. Kroetz, Kathleen M. Giacomini. Pharmacol Rev 58(1): 3-­‐4, 2006. Functional Genomics of Membrane Transporters in Human Populations. Thomas J. Urban*, Ronnie A. Sebro*, Evan H. Hurowitz, Leah L. Lagpacan, Neil Risch, Kathleen M. Giacomini. Genome Res 16(2): 223-­‐30, 2006. The Human Organic Anion Transporter 3 (OAT3; SLC22A8): Genetic Variation and Functional Genomics. Andrew R. Erdman, Lara M. Mangravite, Thomas J. Urban, Leah L. Lagpacan, Richard A. Castro, Melanie de la Cruz, Conrad C. Huang, Susan J. Johns, Michiko Kawamoto, Douglas Stryke, Wendy Chan, Travis R. Taylor, Elaine J. Carlson, Thomas E. Ferrin, Claire M. Brett, Esteban G. Burchard, Kathleen M. Giacomini. Am J Physiol Renal Physiol 290(4): F905-­‐12, 2006. Transport of Drugs in the Kidney by the Human Organic Cation Transporter 2, OCT2, and its Genetic Variants. Tomoe Fujita, Thomas J. Urban, Maya K. Leabman, Kazumi Fujita, Kathleen M. Giacomini. J Pharm Sci 95(1): 25-­‐36, 2006. Haplotype Diversity and Ethnic-­‐Specific Allele Frequencies at the OCTN Locus: Implications for the Genetics of Crohn’s Disease. Thomas J. Urban, Neil Risch, Kathleen M. Giacomini. Inflamm Bowel Dis 11(1):78-­‐9, 2005. Functional and Genetic Diversity in the Concentrative Nucleoside Transporter, SLC28A1, in Human Populations. Jennifer H. Gray, Lara M. Mangravite, Ryan P. Owen, Thomas J. Urban, Wendy Chan, Elaine J. Carlson, Conrad C. Huang, Michiko Kawamoto, Susan J. Johns, Douglas Stryke, Thomas E. Ferrin, and Kathleen M. Giacomini. Mol Pharmacol 65(3):512-­‐9, 2004. Natural Variation in Human Membrane Transporter Genes Reveals Evolutionary and Functional Constraints. Maya K. Leabman, Conrad C. Huang, Joseph DeYoung, Elaine J. Carlson, Travis R. Taylor, Melanie M. de la Cruz, Susan J. Johns, Douglas Stryke, Michiko Kawamoto, Thomas J. Urban, Deanna L. Kroetz, Thomas E. Ferrin, Andrew G. Clark, Neil Risch, Ira Herskowitz, Kathleen M. Giacomini; Pharmacogenetics Of Membrane Transporters Investigators. Proc Natl Acad Sci USA 100(10):5896-­‐
901, 2003. Book Chapters 1. Drug-­‐induced Liver Injury. Thomas J. Urban, Hans Tillmann. In: Handbook of Pharmacogenomics and Stratified Medicine, Padmanabhan Sandosh, ed., Elsevier B.V., Amsterdam, Netherlands, 2014. 2. Organic Cation Transporters (OCTs). Thomas J. Urban, Kathleen M. Giacomini. In: Drug Transporters: Molecular Characterization and Role in Drug Disposition, Guofeng You and Marilyn E. Morris, eds., John Wiley & Sons, Inc., Hoboken, NJ, 2007. Invited Oral Presentations 1. Human Genetic Studies of Tolvaptan-­‐Induced Liver Injury. Presented at the Otsuka Tolvaptan Research Forum, Philadelphia, PA, September 17th, 2014. Thomas J. Urban
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2. Genome-­‐wide Association Study of Response to Sofosbuvir plus Ribavirin in Patients with HCV Genotype 2/3 Infection. Presented at the Duke Molecular Genetics and Microbiology Research Meeting, Durham, NC, February 19th, 2014. 3. Genome-­‐wide Investigation of Viral and Drug-­‐induced Liver Disease. Presented at the UNC Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics Seminar Series, Chapel Hill, NC, October 8th, 2013. 4. Next-­‐generation Sequencing and Adverse Drug Reactions. Presented at the 10th International Meeting of the International Society for the Study of Xenobiotics, Toronto, Canada, October 1st, 2013. 5. Host Genetics of HCV: Relevance for the Study of HCV in Africa. Presented at the inaugural HepNet conference in Kumasi, Ghana, August 12th, 2013. 6. Genetics of Viral and Drug-­‐Induced Liver Disease. Presented at the Carolinas Healthcare System Research Seminar, Charlotte, NC, May 7th, 2013. 7. Genome-­‐wide Approaches to Investigate Severe Drug Toxicities in Humans. Presented at the RTP Drug Metabolism Discussion Group Winter Symposium, Durham, NC, February 28th, 2013. 8. Genome-­‐wide Approaches to the Study of Viral and Drug-­‐Induced Liver Disease. Presented at the Indiana University School of Medicine, Human Genetics Seminar, Indianapolis, IN, January 18th, 2013. 9. Exploring Genomics and Genome Variation. Presented at Bristol-­‐Myers Squibb, Lawrenceville, NJ, December 3rd, 2012. 10. Genome-­‐wide Approaches to Identify Genes Important in Severe Adverse Drug Reactions. Presented at the 2nd “Mitigation Strategies for Reactive Metabolites” conference, Boston, MA, November 29th, 2012. 11. Pharmacogenetics and Risk for Drug-­‐Induced Liver Injury (DILI). Presented at the 2012 AASLD Postgraduate Course, Boston, MA, November 9th, 2012. 12. Genetics of Viral and Drug-­‐Induced Liver Disease. Presented at the University of Michigan Department of Human Genetics Seminar Series, Ann Arbor, MI, September 11th, 2012. 13. Host Genetics of HCV Treatment Response: from Discovery to Delineation. Presented at the University of Michigan Division of Gastroenterology Grand Rounds, Ann Arbor, MI, September 11th, 2012. 14. Pharmacogenetics of Viral and Drug-­‐Induced Liver Disease. Presented at the 21st Irwin M Arias Symposium, “Bridging Basic Science and Liver Disease”, sponsored by the American Liver Foundation, Boston, MA, November 2nd, 2011. 15. A Genome-­‐Wide Association Study Identifies Potential Susceptibility Loci for Hepatotoxicity Due to Various Drugs. Presented at the 2011 Digestive Disease Week, Chicago, IL, May 8th, 2011. 16. The Functional Basis of ITPA Protection Against Ribavirin-­‐induced Anemia. Presented to the Duke University Department of Molecular Genetics and Microbiology, 2010 Annual Retreat, Durham, NC, September 25th, 2010. 17. IL28B, The Funtional and Biological Story: What do we know so far? Presented at “Pharmacogenetics and Hepatitis C: Unraveling the Pieces of the Puzzle”, McLean, VA, June 4th, 2010. 18. A Genome-­‐wide Perspective on Risk for Serious Adverse Drug Reactions. Presented to the Department of Clinical Pharmacology, Vanderbilt University, Nashville, TN, May 4th, 2010. 19. Whole-­‐genome Sequencing in Valproate-­‐induced Liver Injury. Presented at the Duke Clinical Research Institute Research Conference, Durham, NC, April 27th, 2010. 20. Genetics Studies in the Drug-­‐Induced Liver Injury Network. Presented at the AASLD/PhRMA/FDA-­‐
sponsored meeting, “Drug-­‐Induced Liver Injury: Getting the Medicine and Science Together”, Silver Spring, MD, March 24th, 2010. 21. Exploring the Mechanism Behind the IL28B/HCV Genetic Association. Presented at the 4th Annual Retreat of the Duke University Institute for Genome Sciences and Policy (IGSP), Durham, NC, October 28th, 2009. Thomas J. Urban
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22. A Genome-­‐Wide Association Study of Drug-­‐Induced Liver Injury (DILI). Presented at the Drug-­‐
Induced Liver Injury Network 2009 Meeting, Crystal City, VA, October 7th, 2009. 23. CCL3L1 Copy Number is not Associated with HIV-­‐1 Infection Risk or Outcomes in Treatment-­‐Naïve Adult Patients. Presented at the Center for HIV/AIDS Vaccine Immunology (CHAVI) 5th Annual Retreat, Durham, NC, October 6th, 2009. 24. Targeted Sequencing in Epilepsy Risk-­‐associated Copy Number Variant Regions. Presented at the EPIGEN International Consortium 4th Annual Meeting, Brussels, Belgium, September 4th, 2009. 25. Pharmacogenetics in Epilepsy. Presented at the 10th Anniversary Symposium of the Center for Multicultural and Community Affairs, Mt. Sinai Medical Center, New York, NY, November 17th, 2008. 26. Pharmacogenetics in the EPIGEN Program. Presented at the EPIGEN Consortium 3rd Annual Meeting, Hertfordshire, UK, June 6th, 2008. 27. Genetic Control of HLA-­‐C Expression and Splicing. Presented at the Center for HIV/AIDS Vaccine Initiative 3rd Annual Retreat, Durham, NC, October 1st, 2007. Thomas J. Urban
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Research Support ACTIVE 5U01-­‐DK065176-­‐09 (Barnhart) 07/01/13-­‐06/30/18 3.00 cal mos National Institutes of Health $1,442,808 Coordinating Center for the Drug Induced Liver Injury Network: DILIN NIDDK is establishing a network of clinical centers to identify cases of drug-­‐induced hepatotoxicity. Operating definitions will be developed, cases will be identified, clinical data will be collected, and biological samples will be stored for future genetic analyses. The DCRI is serving as the Data Coordinating Center for this study. Role: Co-­‐Investigator 3R01-­‐GM041935-­‐19 (Brouwer) 07/01/11-­‐06/30/19 0.60 cal mos National Institutes of Health (UNC-­‐Chapel Hill) $10,717 Altered Hepatic Disposition of Anionic Drugs: Mechanisms The major goals of this project are to re-­‐sequence genes to identify putatively functional genetic variants in genes encoding hepatic drug transporters of drugs and bile acids; computational predictions of drug-­‐transporter interactions including interactions with variant amino acid sequences and functional assessment of variant transporter activity in cell culture systems. Role: Co-­‐investigator PENDING: No Number (Hawke) 07/01/15-­‐06/30/20 0.9 cal mos National Institutes of Health $6,998,291 UNC-­‐RTI Collaborative Center for Natural Product-­‐Drug Interactions The overarching goal of the proposed UNC-­‐RTI Center for Natural Product-­‐Drug Interactions is to develop and promote new research methods and practices regarding investigations on the concomitant use of medications and natural products. The Center will be composed of four Cores (i.e. Administrative, Pharmacology, Analytical, and Informatics) with researchers from a variety of fields including clinical, translational sciences, integrative medicine, and health services. The Center’s primary aims are to select and direct investigation of 4-­‐6 natural products with high potential for pharmacokinetic drug interactions, create statements of work for each selected natural product, establish a set of best practice guidelines for future studies of natural product-­‐drug interactions, and disseminate the Center’s findings. Additionally, the Center will establish a data repository to organize and archive the Center’s findings, which will be publically available. Ultimately, the Center will both stimulate and instruct scientists from different fields to engage in the development of rigorous scientific methods that will lead to greater mechanistic understanding and prediction of pharmacokinetic interactions between natural products and drugs. Role: Co-­‐investigator No Number (Watkins) 07/01/14-­‐06/30/19 0.6 cal mos National Institutes of Health Induced Pluripotent Stem Cell Approaches to Understand Idiosyncratic Hepatotoxicity The major goal of this project is to uncover mechanisms for idiosyncratic drug-­‐induced liver injury by using organotypic cell culture models of liver derived from induced pluripotent stem cells, including cells from patients who experienced severe hepatotoxicity. Whole-­‐exome sequence data from the same patients will be compared with the cellular/molecular phenotype data to identify mutations in genes that are found to be dysregulated in cellular models of liver injury. Role: Co-­‐investigator Thomas J. Urban
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PAST: CHGV5 (Urban) 7/01/13-­‐06/30/14 3.0 cal mos Gliead Sciences, Inc. $412,690 Human GWAS Study of Predictors of Response to Tenofovir DF in CHB Patients The major goals of this project are to perform a genome-­‐wide association study and whole-­‐genome sequencing of select patients, to identify possible genomic predictors of hepatitis B virus (HBV) serum antigen loss in patients treated with tenofovir disoproxil fumarate. CHGV4 (Urban) 10/01/12-­‐08/30/14 0.6 cal mos Gliead Sciences, Inc. $579,239 Whole-­‐genome Analysis of Response to Sofosbuvir in the Treatment of Chronic HCV Infection The major goals of this project are to perform a genome-­‐wide association study and targeted or whole-­‐genome sequencing, to identify genetic predictors of response to combination therapy with sofosbuvir and ribavirin in patients with genotype 2/3 HCV infection. 1R03DK096121-­‐01 (Urban) 07/01/12-­‐06/30/14 0.60 cal mos University of Denver $5,788 Ribavirin depletes endogenous nucleotide pools The major goal of this project is to understand ribavirin’s pharmacology to improve the treatment of chronic hepatitis C. UCB Cimzia (Goldstein) 01/01/12-­‐11/30/13 1.2 cal mos UCB Celltech $1,141,588 Cimzia Biomarker Studies This project employs a combination of genome-­‐wide genotyping, epigenome-­‐wide methylation profiling, and whole-­‐exome sequencing to identify biomarkers predictive of response to certolizumab pegol (Cimzia) in patients with rheumatoid arthritis. Role: Co-­‐investigator CHGV3 (Urban) 3/01/12-­‐08/31/13 0.36 cal mos Gliead Sciences, Inc. $16,518 Genomic Analysis of Aplastic Anemia related to combination therapy with Interferon alpha and/or GS-­‐9190 The major goals of this project are to perform whole-­‐genome sequencing to identify possible genomic predictors of aplastic anemia associated with the combination treatment. CHGV2 (Urban) 12/01/11-­‐05/31/12 0.24 cal mos Gliead Sciences, Inc. $143,125 Evaluation of elevated serum bilirubin in patients receiving GS-­‐9256 The major goals of this project are to run a Genome-­‐wide Association Study (GWAS), using microarray technology to sequence and identify polymorphisms that are associated with elevated serum bilirubin in the presence of GS-­‐9256 exposure. 3U01-­‐DK-­‐065176-­‐07S2 (Barnhart) 1/31/2011-­‐1/31/2012 1.80 cal mos National Institutes of Health $1,442,808 Coordinating Center for the Drug Induced Liver Injury Network (DILIN): INH-­‐DILI ARRA Supplement This supplement to the Drug Induced Liver Injury Network award supported whole-­‐exome sequencing of 32 individuals with severe liver injury due to isoniazid, for the purpose of identifying rare, functional genetic variation predictive of this toxicity. Thomas J. Urban
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Role: Co-­‐Investigator 5U19-­‐AI067854-­‐07 (Haynes) 07/14/05-­‐06/30/12 1.20 cal mos National Institutes of Health $1,217,700 Center for HIV/AID Vaccine Immunology (CHAVI) Project goals for Aim 4: To elucidate host genetic differences affecting susceptibility to HIV-­‐1 infection and disease progression in acute and early HIV-­‐1 infection and translate these findings into rational vaccine design. Role: Investigator 5R21-­‐DK089464-­‐02 (Urban) 07/01/10-­‐04/30/12 6.00 cal mos National Institutes of Health $148,500 Complete sequencing in drug-­‐induced liver injury The project includes whole-­‐genome sequencing of 20 individuals who have experienced severe liver injury due to the antibiotic combination amoxicillin/clavulanate, discovery of novel rare genetic variants, and testing for association with drug-­‐induced liver injury in large cohorts of cases and control subjects, with the goal of identifying predictive genetic markers for this severe drug toxicity. Duke Clinical Research Institute Biomarker Discovery Award (Urban) 5/1/2010 – 4/30/2011 Whole-­‐genome sequencing in valproate-­‐induced liver injury The project includes whole-­‐genome sequencing of up to 14 individuals who have experienced severe liver injury due to the antiepileptic drug valproic acid, discovery of novel rare genetic variants, and testing for association with drug-­‐induced liver injury in large cohorts of cases and control subjects, with the goal of identifying predictive genetic markers for this severe drug toxicity. Thomas J. Urban
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