1 CURRICULUM VITAE Tzyh-Chang (TC) Hwang Date of birth: Feb. 14, 1957 Office address: Membrane Biophysics Laboratory, DCRC Research Park University of Missouri-Columbia, Columbia, MO 65211. Telephone: 573-882-2181 Education: 1975 - 1982 1984 - 1986 1986 - 1990 Marital status: Married, two children. Fax: 573-884-4232 e-mail: [email protected]. National Yang-Ming Medical School M.D. National Taiwan University School of Medicine M.S. Department of Physiology, School of Medicine The Johns Hopkins University Ph.D. Professional Experience: 1980 - 1982 Internship, Veteran General Hospital, Taipei, Taiwan R. O. C. 1982 - 1984 Surgeon Officer and Lieutenant Officer, R. O. C. Army 1984 - 1986 Teaching Assistant, Department of Physiology, National Yang-Ming Medical College 1990 - 1993 Postdoctoral Associate, Laboratory of Cardiac/Membrane Physiology The Rockefeller University 1993 - 1994 Assistant Professor, Laboratory of Cardiac/Membrane Physiology The Rockefeller University 1994 - 1999 Assistant Professor, Department of Physiology, University of Missouri-Columbia 1994 Research Investigator, Dalton Cardiovascular Research Center 1999 2004 Associate Professor, Department of Physiology, University of Missouri-Columbia 2001 – 2002 Visiting Professor, Department of Physiology and Biophysics, Cornell Medical School 2004 Professor, Department of Medical Pharmacology and Physiology, University of Missouri 2008 – 2009 Visiting Professor, Institute of Biophotonics, National Yang Ming University Honors and Awards: 1984 Service Award by R. O. C. Army 1986 - 1990 Fellowship, Department of Physiology, The Johns Hopkins University 1989 FASEB Award, Cell and General Physiology, American Physiological Society 1990 Certificate of Merit, Young Investigator Day, The Johns Hopkins University 1991- 1994 Ella Fitzgerald Research Fellowship, New York Heart Association 1998 Excellence in Medical Student Education, MU Medical School. 1999 Excellence in Medical Student Education, MU Medical Student Affair Council. 1999 Nomination for Howard Hughes Assistant Investigatorship 2000 Professor-for-a-Day, School of Engineering, University of Missouri 2000 Paul Cranefield Award, Society of General Physiologists 2001 Excellence in Medical Student Education, MU Medical School 2001 Service Award, American Medical Student Association, University of Missouri 2 2001 2007 2008 2009 Order of Socrates, MU Medical School Honorary Visiting Professorship, Osaka Medical College, Japan Visiting Professorship, Harbin Medical University, China Outstanding Alumni Award, National Yang Ming University, Taiwan National/International Service 1999 Cardiovascular A Study Section, NIH, ad hoc reviewer. 2000 General Medicine B Study Section, NIH, ad hoc member. 2003 - 2006 Molecular, Cellular and Developmental Neurosciences 3 Study Section, NIH, regular member. 2003 - present Editorial Board, Journal of General Physiology 2006 - present Editorial Board, Biophysical Journal 2006 - 2007 Biophysics of Neural Systems Study Section, regular member. 2006 American Heart Association, “Cell Metabolism and Transport” Study Section. 2006 - present Consultant, Cystic Fibrosis Foundation Therapeutics 2007 Ad hoc member, Board of Scientific Council, NIH/NINDS. 2008 Ad hoc member, Special Emphasis Panel/Scientific Review Group ZRG1 RUS-C 2010 – present Member of College of CSR Reviewers, NIH. Local Service 2004 – present Member, Graduate Educational Committee, Medical Pharmacology and Physiology 2004- present Member, Tenure and Promotion committee, Dalton Cardiovascular Research Center Grant support (Total direct) as P.I. or Mentor: 1994 - 1996 Grant-in-aid, American Heart Association, Missouri Affiliate. $50,000 1995 - 1996 MU Research Board, $34,000 1995 - 1997 MU Molecular Biology Postdoc. Fellowship (Dr. Fei Wang), $47,000 1996 - 2000 NIH FIRST Award, $280,000 1996 - 1998 New Investigator Award, Cystic Fibrosis Foundation, $60,000 1996 - 1999 NIH/CFF RFA, $300,000 1997 - 1999 Postdoc. fellowship (Dr. Fei Wang), American Heart Association, Missouri Affiliate, $55,000. 1997 - 1998 Trainingship (Shawn Zeltwanger), Cystic Fibrosis Foundation, $1,500 1998 - 1999 MU Molecular Biology Postdoc. Fellowship (Dr. Zhen Zhou), $23,500 1999 - 2001 Postdoc. fellowship (Dr. Zhen Zhou), American Heart Association, Missouri Affiliate, $55,000. 1999 - 2003 NIHR01, NIDDK, “Molecular pathophysiology of cystic fibrosis”, $572,637 1999 - 2000 Cystic Fibrosis Foundation, $75,000 2000 - 2002 Postdoctoral fellowship (Dr. Allan Powe), Merck Foundation, $70,000 2000 - 2002 Grand-in-aid, American Heart Association (declined after one year of funding), $65,445 2001 - 2005 AHA Established Investigatorship (declined after three months of funding), $300,000 2000 - 2004 NIHR01, NHLBI, “Gating of CFTR chloride channels by ATP hydrolysis”, $700,000. 2000 - 2001 Trainingship (Lesley Nichols), Cystic Fibrosis Foundation, $1,500 2001 - 2004 Postdoc. fellowship (Dr. Zhen Zhou), Cystic Fibrosis Foundation, $100,000. 2002 - 2007 NIHK25 (Dr. Xiaoqin Zou), $500,000. 2003 - 2006 NIH NRSA Award (Dr. Silvia Bompadre), $150,348. 3 2003 - 2005 2003 – 2007 2005 – 2006 2006 - 2007 2006 – 2010 2006 – 2009 2006 – 2009 2008 – 2013 2009 – 2011 AHA Postdoctoral fellowship (Dr. Tomohiko Ai), $80,685. NIHR01, NIDDK, “Molecular pathophysiology of cystic fibrosis”, $640,000 Cystic Fibrosis Foundation, $75,000 NIHS10, “Confocal equipment for biomedical and nanomedicine research”, $402,030 NIHR01 NHLB, “Gating of CFTR chloride channels by ATP hydrolysis”, $933,056 NIHK01 (Dr. Silvia Bompadre), NIDDK, “Molecular physiology and pharmacology of CFTR chloride channels” $300,000 CFFT, “Structure-guided physiological screening of F508 CFTR correctors”. $1,349,781 NIHR01, NIDDK, “Molecular pathophysiology of cystic fibrosis”, $1,014,155 CFF Postdoctoral Fellowship (Dr. Zoia Kopeikin), “On the mechanism of CFTR inhibition by CFTRinh-172.” $86,100 Grant support (Total direct) as Co-P.I.: 1997 - 1998 Clinical Research Committee Award (P.I. Dr. Peter Konig), Cystic Fibrosis Foundation, “Effects of genistein on F508 CFTR”, $60,262, 5% effort. 1997 - 2001 NIHR01 (P.I. Dr. Mark Milanick), “Cytosolic modulation of plasma membrane ion transport”, $696,039, 5% effort. 1995 - 2000 NIH Training Grant (P.I. Dr. Virginia Huxley), “Cardiovascular and renal physiology, pharmacology and biochemistry”, $704,666, 5% effort. 1999 - 2001 Research Grant (P.I. Dr. Fei Wang), Cystic Fibrosis Foundation, $100,350. 1999 - 2001 Research Grant (P.I. Dr. Layla Al-Nakkash), Cystic Fibrosis Foundation, $88,350. 2001 - 2003 NIHC06 (P.I.: Dr. Edward Blaine), "Conversion of Shell Space at the Dalton Cardiovascular Research Center", $1,036,000. 2002 - 2005 NIH training grant (P.I. Dr. Virginia Huxley), “Cardiovascular & Renal Physiology, Pharmacology & Biochemistry”, $648,270, 3% effort. 2003 - 2006 NIHR01 (P.I. Dr. Mark Milanick), “Cytosolic modulation of plasma membrane ion transport”, $615,000, 5% effort. 2004 – 2005 NIH (PI. Dr. Kevin Gillis), Nanomedicine Center Concept Development Award, Phase I, $36,000. 2006 – 2008 Research Grant (P.I. Dr. Zhen Zhou), Cystic Fibrosis Foundation, $80,000 2006 – 2008 Research Grant (P.I. Dr. Silvia Bompadre), Cystic Fibrosis Foundation, $160,000 2007 – 2009 NIHR21 (P.I. Dr. Dongsheng Duan), “Novel hybrid AAV vectors for cystic fibrosis gene therapy”, $254,277, 5% effort. Graduate students supervised: 1995 - 1998 Shawn Zeltwanger, Ph.D. (Physiology) 2003 - 2006 Jeong Han Cho (Bioengineering) 2005 - 2009 Xiaohui Wang (MPP) 2007 Ming-Feng Tsai (MPP) 2007 Yonghong Bai (Bioengineering) 2009 Kang-Yang Jih (MPP) Postdoctoral fellow: 4 1995 - 1999 Fei Wang (Rockefeller University, New York) 1996 - 1999 Layla Al-Nakkash (University of Newcastle-Upon-Tyne, England) 1997 - 1998 Guo-Tang Wang (Peiking Medical University, Peiking) 1998 - 2002 Allan Powe (Rockefeller University, New York) 1998 - 2005 Zhen Zhou (University of Michigan, Ann Arbor) 2000 - 2006 Silvia Bompadre (University of Washington, Seattle) 2001 - 2003 Tomohiko Ai (Kyoto University, Japan) 2006 - 2008 Hiroyasu Shimizu (Osaka Medical College) 2006 - 2009 Hao-Yang Liu (Wuhan University, China) 2007 - present Zoia Kopeikin (University of Missouri-Columbia) Memberships: Biophysical Society Society of General Physiologist American Physiological Society Invited Speaker: 1992 Department of Pharmacology, Columbia University, School of Medicine. 6th Annual North American Cystic Fibrosis Conference. 1993 Department of Physiology, Cornell Medical School. Cystic Fibrosis Research Group, The Johns Hopkins Medical School. Department of Physiology, Oxford University, United Kingdom. XXXll Congress of the International Union of Physiological Sciences Max Planck Institute for Biophysics, Frankfurt, Germany. Department of Physiology, University of Cologne, Cologne, Germany. 1994 International Society for Heart Research, London, Ontario, Canada. 48th Annual Symposium, Society of General Physiologists 1995 Gordon Research Conference, New Hampshire Department of Pharmacology, University of Missouri-Columbia 1996 Williamsburg Meeting, Cystic Fibrosis Foundation 10th Annual North American Cystic Fibrosis Conference Department of Molecular and Cellular Physiology, Yale University. 1997 Department of Veterinary Biomedical Sciences, University of Missouri-Columbia Department of Physiology, Kyoto University, Japan Department of Physiology, Tzu-Chi Medical College, Taiwan Department of Physiology, National Chung-Kung University, Taiwan Department of Physiology, National Yang-Ming Medical University, Taiwan Alfred duPond Institute, Delaware Center for Human Gene Therapy, University of Pennsylvania, Philadelphia Williamsburg Meeting, Cystic Fibrosis Foundation Department of Molecular Biophysics and Physiology, Rush Medical Center, Chicago 11th Annual North American Cystic Fibrosis Conference Genzyme Corp. Hamingham, MA. 1998 Williamsburg Meeting, Cystic Fibrosis Foundation 12th Annual North American Cystic Fibrosis Conference 1999 Department of Physiology, National Taiwan University 5 2000 2001 2002 2003 2004 2005 2007 2008 2009 Department of Physiology, National Yang-Ming Medical University, Taiwan Department of Biological and Agricultural Engineering, University of Missouri-Columbia Department of Physics, University of Missouri-Columbia Nutrition Group, University of Missouri-Columbia Neurobiology Group, University of Missouri-Columbia Department of Physiology, Emory University Gordon Conference Alfred duPond Institute, Delaware Department of Physics, Wuhan University, China Department of Physiology and Biophysics, University of Colorado Osaka Medical College Department of Physiology, Kyoto University Williamsburg Meeting Department of Physiology and Biophysics, Cornell Medical College Department of Physiology, University of California, Davis Department of Physiology, Robert Wood Johnson Medical School Institute of Human Gene Therapy, University of Pennsylvania Department of Physiology, Johns Hopkins Medical School Department of Biological Engineering, University of Missouri-Columbia Department of Physics, University of Missouri-Columbia Gordon Conference European Cystic Fibrosis Conference, Tomar, Portugal Department of Physiology, Osaka Medical College, Japan Osaka University of Pharmatheutical Science, Japan Veteran General Hospital, Taichun, Taiwan Department of Physiology, National Cheng-Kung University, Taiwan Institute of Molecular Biology, National Chung-Cheng University, Taiwan North American Cystic Fibrosis Conference Gordon Research Conference North American Cystic Fibrosis Conference National Yang-Ming Medical University, Institute of Neuroscience Special Satellite Meeting on Anion Transport for the Society of Physiologists, United Kingdom Department of Pharmacology, National Yang-Ming Medical University Department of Physiology, Osaka Medical College, Japan Department of Internal Medicine, Taichun Veteran General Hospital Osaka University of Pharmatheutical Science, Japan Department of Anesthesiology, Washington University Department of Physiology, University of Illinois, Urbana Champaign Life Science Institute, Northeast Normal University, Changchun, China Symposium speaker, Joint meeting of the Physiological Society, the Chinese Association for Physiological Societies, and the American, Australian and Canadian Physiological Societies, Beijing China. Department of Physiology, Chinese University of Hong Kong Harbin Medical University Department of Pharmacology, Keio University, Japan Department of Biology, Hong Kong University of Science and Technology 6 2010 Institute of Biomedical Sciences, Academia Sinica, Taiwan, ROC European Cystic Fibrosis Conference, Portugal Keynote speaker, 14th Annual Conference of the Biophysical Society of ROC, Taiwan Keynote speaker, Annual Conference for Collaborative Projects between National Taiwan University Hospital and Veteran General Hospital, Taipei, Taiwan Kyoto Prefectural University of Medicine IUPS2009, Kyoto, Japan Special Satellite Meeting on Anion Transport for IUPS, Okazaki, Japan Fu-Jen University, School of Medicine, Taipei, Taiwan Department of Physiology, Xian JiaoTong University, School of Medicine, Xian, China Department of Physiology and Pharmacology, Chang Gung University, Taiwan Department of Electrical Engineering, National Taiwan University Bethune Second Hospital, Jilin University, China Department of Cell Physiology and Molecular Biophysics, Texas Tech University Meeting Chair: 1994 Biophysical Meeting 1997 11th Annual North American Cystic Fibrosis Conference 2003 Society of General Physiologists Meeting, Woods Hole, Massachusetts 2005 Special Satellite Meeting on Anion Transport for the Society of Physiologists, Bristol, United Kingdom 2006 Williamsburg Conference, Cystic Fibrosis Foundation 2007 FASEB Meeting, Washington DC 2009 Special Satellite Meeting on Anion Transport for IUPS, Okasaki, Japan Journal Reviewer: American Journal of Physiology (cell physiology), American Journal of Physiology (heart and circulation), Journal of General Physiology, Neuron, Journal of Membrane Biology, Journal of Biological Chemistry, Journal of Pharmacology and Experimental Therapeutics, Journal of Molecular and Cellular Cardiology, Canadian Journal of Physiology and Pharmacology, Biophysical Journal, Journal of Physiology, Brain Research, American Journal of Physiology (Lung, Cell and Mole), Proceedings of National Academy of Sciences, USA, FEBS Lett., Nature, Biochemical Journal, Bioorganic and Medicinal Chemistry, Nature Structural Biology, PLoSONE, Biosci Report.. Grant Reviewer: Cystic Fibrosis Trust (United Kingdom), Cystic Fibrosis Foundation, Cystic Fibrosis Research Inc., MU Research Board, Veteran Affairs, NIH (CVA, ad hoc reviewer), NIH (GMB, ad hoc member), NIH (MCDN3, regular member), Philips Morris External Research Program, Italian Telethon Foundation, American Heart Association (National Center), Dutch Digestive Foundation, Wellcome Trust (United Kingdom), National Science Foundation, Academia Sinica (ROC). Publications: PAPERS: 1. Tong J. Chen, Tzyh-Chang Hwang, Chiun Chien Huang, Guey Mei Jow, and John Yuh-lin Yu. (1989) Deciduomal estrogen and progesterone receptors in unilateral pregnant hamsters. Endocrinology , 125:302-307. 7 2. Tzyh-Chang Hwang, Luo Lu, Pamela Zeitlin, Dieter Gruenert, Richard Huganir and William B. Guggino.(1989). Chloride channels in cystic fibrosis: Lack of activation by protein kinase C and cAMPdependent protein kinase. Science, Wash. DC. 244:1351-1353. 3. Luo Lu, Chahrzad Mintrose-Refizadeh, Tzyh-Chang Hwang and William B. Guggino. (1990) A delayed rectifier potassium current in Xenopus oocyte. Biophys. J. 57:1117-1123. 4. Tzyh-Chang Hwang, Sandra E. Guggino and William B. Guggino. (1990). Direct modulation of secretory chloride channels by arachidonic and other Cis-unsaturated fatty acids. Proc. Natl. Acad. Sci. USA. 87:5706-5709. 5. Tzyh-Chang Hwang, Minoru Horie, Angus C. Nairn and David C. Gadsby. (1992) Roles of GTPbinding proteins in the regulation of mammalian cardiac chloride conductance. J. Gen. Physiol. 99: 465-489. 6. Minoru Horie, Tzyh-Chang Hwang and David C. Gadsby. (1992). Pipette GTP is essential for receptormediated regulation of Cl current in dialysed myocytes from guinea-pig ventricle. J. Physiol. 455:235245. 7. Georg Nagel, Tzyh-Chang Hwang, Kent Nastiuk, Angus C. Nairn And David C. Gadsby. (1992). The protein kinase A-regulated cardiac Cl channel resembles CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). Nature. 360:81-84. 8. Tzyh-Chang Hwang, Marie E. Egan and William B. Guggino. (1992). Kinetic interaction of fatty acids with outwardly rectifying chloride channels. Cell. Physiol. Biochem. 2:308-315. 9. Tzyh-Chang Hwang, Minoru Horie and David C. Gadsby. (1993) Functionally distinct phospho-forms underlie incremental activation of PKA-regulated Cl conductance in mammalian heart. J. Gen. Physiol. 101:629-650. 10. David C. Gadsby, Tzyh-Chang Hwang, Minoru Horie, Georg Nagel and Angus C. Nairn. (1993) Cardiac chloride channels: incremental regulation by phosphorylation/dephosphorylation. Ann. N. Y. Acad. Sci. 707:259-274. 11. Tzyh-Chang Hwang, Georg Nagel, Angus C. Nairn and David. C. Gadsby. (1994). Regulation of the gating of CFTR Cl channels by phosphorylation and ATP hydrolysis. Proc. Natl. Acad. Sci. USA. 91:4698-4702. 12. Thomas Baukrowitz, Tzyh-Chang Hwang, Angus C. Nairn and David. C. Gadsby. (1994). Coupling of CFTR channel gating to an ATP hydrolysis cycle. Neuron. 12:473-482. 13. David C. Gadsby, Tzyh-Chang Hwang, Thomas Baukrowitz, Georg Nagel, Minoru Horie and Angus C. Nairn. (1994). Regulation of CFTR channel gating. Jap. J. Physiol. 44:S183-S192. 14. Iris Yang, Tzu-Hurng Cheng, Fei Wang, Elmer Price and Tzyh-Chang Hwang. (1997). Modulation of CFTR chloride channels by calyculin A and genistein. Am. J. Physiol. 272:C142-C155. 15. Tzyh-Chang Hwang, Fei Wang, Iris Yang, and William W. Reenstra. (1997). Genistein potentiates wild-type and F508 CFTR channel. Am. J. Physiol. 273:C988-C998. 16. Jumming Zhong, Tzyh-Chang Hwang, Richard Adams, and Leona Rubin. (1997). Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs. Am. J. Physiol. 273:H2312H2324. 17. Fei Wang, Shawn Zeltwanger, Iris Yang, Angus Nairn, and Tzyh-Chang Hwang. (1998). Action of genistein on CFTR gating: evidence of two binding sites with opposite effects. J. Gen. Physiol. 111:477490. 18. Layla Al-Nakkash, and Tzyh-Chang Hwang. (1999). Activation of wild-type and F508-CFTR by phosphodiesterase inhibitors. Pflügers Arch. 437:553-561. 19. Shawn Zeltwanger, Fei Wang, Guo-Tang Wang, Kevin Gillis, and Tzyh-Chang Hwang. (1999). Gating of CFTR by nucleoside triphosphates: quantitative analysis of a cyclic gating scheme. J. Gen. Physiol. 8 113:541-554. 20. Fei Wang, Shawn Zeltwanger, Shenghui Hu, and Tzyh-Chang Hwang. (2000). Deletion of phenylalanine 508 causes attenuated phosphorylation-dependent activation of CFTR chloride channels. J. Physiol. 524:637-648.. 21. Layla Al-Nakkash, Shenghui Hu, Min Li, and Tzyh-Chang Hwang. (2001). A common mechanism for CFTR activation by benzimidazolone analogs and genistein. J. Exp. Pharm. Ther. 296:464-472. 22. Zhen Zhou, Shenghui Hu, and Tzyh-Chang Hwang. (2001). Voltage-dependent flickery blockade of an open CFTR channel. J. Physiol. 532:435-448. 23. Peng Chen, Tzyh-Chang Hwang, and Kevin Gillis. (2001).The relationship between cAMP, Ca and transport of CFTR to the plasma membrane. J. Gen. Physiol.118:135-144. 24. Allan Powe, Layla AL-Nakkash, Min Li, and Tzyh-Chang Hwang. (2002). Mutations of the Walker A lysine 464 in CFTR reveal functional interaction between its two nucleotide binding domains. J. Physiol. 539:333-346. 25. Zhen Zhou, Shenghui Hu, and Tzyh-Chang Hwang (2002). Probing an open CFTR pore with organic anion blockers. J. Gen. Physiol. 120:647-662. 26. Tzyh-Chang Hwang, Roger Koeppe, II. and Olaf Andersen (2003). Genistein can modulate channel function by a phosphorylation-independent mechanism: Importance of bilayer mechanics and hydrophobic mismatch. Biochemistry 42:13646-13658. 27. Tomohiko Ai, Silvia Bompadre, Xiaohui Wang, Shenghui Hu, Min Li, and Tzyh-Chang Hwang (2004). Capsaicin potentiates wild-type and mutant CFTR chloride channel currents. Molecular Pharmacology 65:1415-1426. 28. Lane L. Clarke, Lara R. Gawenis, Tzyh-Chang Hwang, Nancy M. Walker, Darren B. Gruis and Elmer M. Price (2004). A Domain Mimic Increases {Delta}F508 CFTR Trafficking and Restores cAMP-Stimulated Anion Secretion in Cystic Fibrosis Epithelia. Am. J. Physiol. 287:C192-199. 29. Tomohiko Ai, Silvia Bompadre, Yoshiro Sohma, Min Li and Tzyh-Chang Hwang (2004). Direct effects of 9-anthracene compounds on CFTR gating. Pflügers Arch. 449:88-95. 30. Silvia G. Bompadre, Tomohiko Ai, Jeong Han Cho, Xiaohui Wang, Yoshiro Sohma, Min Li, and TzyhChang Hwang. (2005). CFTR gating I: Characterization of the ATP-dependent gating of a phosphorylation-independent CFTR channel (R-CFTR). J. Gen. Physiol. 125:361-375. 31. Silvia G. Bompadre, Jeong Han Cho, Xiaohui Wang, Xiaoqin Zou, Yoshiro Sohma, Min Li, and Tzyh-Chang Hwang. (2005). CFTR gating II: Effects of nucleotide binding on the stability of open states. J. Gen. Physiol. 125:377-394. 32. Zhen Zhou, Xiaohui Wang, Min Li, Yoshiro Sohma, Xiaoqin Zou, and Tzyh-Chang Hwang. (2005). High affinity ATP/ADP analogs as new tools for studying CFTR gating. J. Physiol. 569:447457. 33. Zhen Zhou, Xiaohui Wang, Haoyang Liu, Xiaoqin Zou, Min Li, and Tzyh-Chang Hwang. (2006). The two ATP binding sites of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) play distinct roles in gating kinetics and energetics. J. Gen. Physiol. 128:413-422. 34. Silvia G. Bompadre, Yoshiro Sohma, Min Li, and Tzyh-Chang Hwang. (2007). G551D and G1349D, two CF-associated mutations, exhibit distinct gating defects. J. Gen. Physiol. 129(4):28598. 35. Yen-Chin Chao, Shwu-Fen Chang, Shao-Chun Lu, Tzyh-Chang Hwang, Wei-Hsien Hsieh and Jiahorng Liaw. (2007). Ethanol enhanced in vivo gene delivery with non-ionic polymeric micelles inhalation. J. Control Release 118(1):105-17. 36. Silvia Bompadre, Min Li, and Tzyh-Chang Hwang. (2008). P-ATP potentiates G551D-CFTR by 9 binding to the hydrolysis-incompetent site. J. Biol. Chem. 283:5364-5369. 37. K. Mio, T. Ogura, M. Mio, H. Shimizu, T. –C. Hwang, C. Sato, and Y. Sohma. (2008). Threedimensional Reconstruction of Human Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Revealed an Ellipsoidal Structure with Orifices beneath the Putative Transmembrane Domain. J. Biol. Chem. 283(44):30300-30310. 38. Xiaohui Wang, Silvia Bompadre, Min Li and Tzyh-Chang Hwang (2009). Mutations at the signature sequence of CFTR create a cadmium-gated chloride channel. J. Gen. Physiol. 133:67-77. 39. Sheng-You Huang, Diana Bolser, Hao-Yang Liu, Tzyh-Chang Hwang and Xiaoqin Zou. (2009). Molecular modeling of the heterodimer of human CFTR’s nucleotide-binding domains using a protein-protein docking approach. J. Mol. Graph. Model, 27:822-828. 40. Mingfeng Tsai, Hiroyasu Shimizu, Yoshiro Sohma, Min Li, and Tzyh-Chang Hwang (2009). Statedependent modulation of CFTR gating by pyrophosphate. J. Gen. Physiol. 133:405-419. 41. Ming-Feng Tsai, Min Li, and Tzyh-Chang Hwang. (2010). Stable ATP binding mediated by a partial NBD dimer of the CFTR chloride channel. J. Gen. Physiol. 135:399-414. 42. Haruna Miki, Zhen Zhou, Min Li, Tzyh-Chang Hwang, and Silvia Bompadre. (2010). Potentiation of disease-associated CFTR mutants by hydrolysable ATP analogs. J. Biol. Chem. In press. 43. Ming-Feng Tsai, Kang-Yang Jih, Min Li, and Tzyh-Chang Hwang. (2010). Optimization of the composite site 1 rectifies the functional defects of cystic fibrosis related mutant CFTR channels. Submitted. 44. Yonghong Bai, Min Li, and Tzyh-Chang Hwang. (2010). Dual roles of the sixth transmembrane segment of the CFTR chloride channel in gating and permeation. Submitted. REVIEWS and BOOK CHAPTERS: 1. Tzyh-Chang Hwang and David C, Gadsby (1994). Chloride ion channels in mammalian heart. Current Topics in Membrane and Transports. 42:317-346. 2. David C, Gadsby, Georg Nagel and Tzyh-Chang Hwang (1995). CFTR chloride channels in mammalian heart. Ann. Rev. Physiol. 57:387-416. 3. Tzyh-Chang Hwang and David Sheppard (1999). Molecular pharmacology of the CFTR chloride channel. TIPS, 11:448-453. 4. Xiaoqin Zou and Tzyh-Chang Hwang. (2001). ATP hydrolysis-coupled gating of CFTR chloride channels: structure and function. Biochemistry, 40:5579-5586. 5. Allan. C. Powe, Zhen Zhou, Tzyh-Chang Hwang, and G. Nagel. (2002). Quantitative analysis of ATPdependent CFTR gating. Methods in Molecular Medicine, 70-67-98. 6. Sheppard DN, Gray MA, Gong X, Sohma Y, Kogan I, Benos DJ, Scott-Ward TS, Chen JH, Li H, Cai Z, Gupta J, Li C, Ramjeesingh M, Berdiev BK, Ismailov II, Bear CE, Hwang TC, Linsdell P, and Hug MJ. (2004) The patch-clamp and planar lipid bilayer techniques: powerful and versatile tools to investigate the CFTR Cl- channel. J. Cyst. Fibros. Suppl 2: 101-108 7. Zhen Zhou and Tzyh-Chang Hwang. (2007). Gating of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) chloride channels. Advan. Mole. Cell. Biol. 38:145-180. 8. Silvia, Bompadre and Tzyh-Chang Hwang. (2007). CFTR: a chloride channel gated by ATP binding and hydrolysis. Acta Physiolgica Sinica 59(4):431-42. 9. Tsung-Yu Chen and Tzyh-Chang Hwang. (2008). CLC-0 and CFTR: two chloride channels evolved from transporters. Physiol. Rev. 88:351-387. 10. Tzyh-Chang Hwang and David Sheppard. (2009). Gating of the CFTR chloride channel by ATP-driven nucleotide-binding domain dimerisation. J. Physiol. 587:2151-2161. 10 11. Tsung-Yu Chen, Ming-Feng Tsai, and Tzyh-Chang Hwang. (2010). Structures and mechanisms of chloride channels. Submitted. 12. Zhiwei Cai, Yoshiro Sohma, Silvia Bompadre, David, N. Sheppard, and Tzyh-Chang Hwang. (2010). Application of high-resolution single-channel recording to functional studies of cystic fibrosis mutants and small molecule CFTR potentiators. Submitted. ABSTRACTS: 1. Tong J. Chen, Tzyh-Chang Hwang, S. M. Chuang. Maintenance of Deciduomal and Decidual Responses in Pregnant Hamsters. The First Joint Annual Conference of Biomedical Science 1986, Taiwan, R.O.C. p92. 2. Tzyh-Chang Hwang, Luo Lu, Pamela Zeitlin, Dieter Gruenert, Richard Huganir and William B. Guggino. (1989) Activation of Epithelial Cl Channel by Protein Kinase C and cAMP-dependent Protein Kinase. FASEB J. 3:A1149. 3. Tzyh-Chang Hwang, Luo Lu, Pamela Zeitlin, Richard Huganir and William Guggino. (1989) Chloride Channels in Cystic Fibrosis: Lack of Activation by Protein Kinase C and cAMP-dependent Protein Kinase. Ped. Pulmonol. Suppl 4):116. 4. Tzyh-Chang Hwang, Sandra E. Guggino and William B. Guggino. (1990) Arachidonic acid block of epithelial Cl channels in tracheal airway cells. Biophys. J. 57, 88a. 5. Tzyh-Chang Hwang, Minoru Horie, and David C. Gadsby (1991). Persistent activation of chloride current by GTPS in guinea pig ventricular myocytes. Biophys. J. 59, 7a. 6. Minoru Horie, Tzyh-Chang Hwang, and David C. Gadsby (1991). Okadaic acid modulates chloride current activated by cAMP-dependent protein kinase in guinea pig ventricular myocytes. Biophys. J. 59, 90a. 7. Minoru Horie, Tzyh-Chang. Hwang, and David C. Gadsby. (l991) Intra-pipette GTP prevents the rapid rundown of ß adrenoceptor-mediated activation of Cl current in isolated guinea-pig ventricular myocytes J. Physiol., 446, 153P. 8. Minoru Horie, Tzyh-Chang Hwang, and David C. Gadsby. (l992) Forskolin activation of PKAregulated chloride current in guinea pig ventricular myocytes. Biophys. J . 61, A396. 9. Tzyh-Chang Hwang, M. Horie, A. G. Dousmanis, and D. C. Gadsby. (l992). Interactive modulation of PKA-regulated chloride current by forskolin, Gs, and Gi in guinea pig ventricular myocytes. Biophys. J. 61, A395. 10. Georg A. Nagel, Tzyh-Chang Hwang, Allan C. Powe, Angus C. Nairn, and David C. Gadsby. (l992) Chloride channels activated by protein kinase A in giant patches excised from guinea pig ventricular myocytes. Biophys. J. 61, A146. 11. Tzyh-Chang Hwang, M. Horie, A. G. Dousmanis, and D. C. Gadsby. (l992). Regulation of PKAactivated Cl conductance in guinea pig ventricular myocytes: whole-cell studies. J. Gen. Physiol. 100:69a. 12. Georg A. Nagel, Tzyh-Chang Hwang, Angus C. Nairn, and David C. Gadsby. (l992) Regulation of PKA-activated Cl conductance in guinea pig ventricular myocytes: single channel studies. J. Gen. Physiol. 100:70a. 13. Tzyh-Chang Hwang, Georg A. Nagel, Angus C. Nairn, and David C. Gadsby. (1993). Dephosphorylation of cardiac CFTR Cl channels requires multiple protein phosphatases. Biophys. J. 46:A343. 14. Tzyh-Chang Hwang, Georg A. Nagel, Angus C. Nairn, and David C. Gadsby. (1994). Differential regulation of nucleotide binding sites in CFTR by PKA phosphorylation. Biophys. J. 66:A141 15. Georg A. Nagel, Tzyh-Chang Hwang, Angus C. Nairn, and David C. Gadsby. (1994). AMP-PNP delays the closing of CFTR Cl channels opened by ATP. Biophys. J. 66:A141. 11 16. Thomas Baukrowitz, Tzyh-Chang Hwang, Angus C. Nairn, and David C. Gadsby. (1994). 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