professor chen yuan-tsong 陳垣崇 academia sinica, taiwan

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Acknowledgment

The United College Distinguished Visiting Scholar Committee acknowledges with thanks the generous grant from the United College Endowment Fund, which has made possible the visit of Professor Chen, Yuan-Tsong, Academician, Academia Sinica, Taiwan, to United College as our Distinguished Visiting Scholar in 2012-13.

Distinguished Visiting Scholar CommitteeUnited College

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Professor Chen, Yuan-Tsong陳垣崇教授

Academician, Academia Sinica, Taiwan台灣中央研究院院士

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A Warm Welcome to Professor Chen, Yuan-Tsong

It is a great pleasure to welcome Prof. Yuan-Tsong Chen as the United College Distinguished Visiting Scholar of 2012-13.

Prof. Chen graduated with medical degree from National Taiwan University. He then pursued further study to become a medical scientist, and was awarded a PhD from Columbia University, while at the same time, he obtained practicing licenses in Taiwan and the US. From there, he started an extra-ordinary career in Medical Genetics and has been the pioneer during the three recent Eras of advancement in the diagnosis and treatment of genetic diseases.

Early in his career, Prof. Chen worked in the most prestigious institutes in United States, like the NIH, and later was appointed to a tenured position in the School of Medicine at Duke University. He headed the clinical genetics section and diagnostic laboratory since the 1980’s and was promoted to Chair Professor and Chief of Medical Genetics in the 1990’s. He also helped to develop Duke’s Newborn Screening program, which set the standard for modern Newborn Screening using the latest technology of mass spectrometry. After the turn of the century, Prof. Chen returned to Taiwan and became the Director of the Institute of Biomedical Sciences at the Academia Sinica. Prof. Chen recently stepped down from the Directorship after serving 10 years in that position, but he maintains his research team in the Institute.

The positions and appointments in which Prof. Chen has served do not fully reflect his achievements in the field of medical genetics. It is a life-

time award for a scientist if his or her work leads to one single discovery. In the case of Prof. Chen, he made at least four major discoveries. I do not have the words to fully describe all of his achievements, and yet I must try.

Let’s go back to 1980s, and start with his work with patients with glycogen storage disease (GSD) type 1 in the genetics clinic. The prevalent view of genetic diseases was that they were diseases of no cure. There was no way one could change the gene. These patients came in with a very big tummy because their liver could not break down glycogen (a form of carbohydrate polymer used by the cell to store carbohydrates) to glucose (the form that can be used by the cells). These patients accumulated glycogen ( resulting in huge liver) but also suffered from an insufficient supply of glucose (meaning they could faint easily and potentially die). Prof. Chen invented a method to feed these children with corn starch, which has become the standard therapy today. Corn starch can be digested efficiently by these patients and provides a longer lasting supply of glucose. Subsequently, he discovered the common mutations causing this disease and the gene causing another types of GSD. This happened in the Era of Molecular Diagnosis, when one could make accurate diagnoses of rare familial genetic diseases.

There is another type of glycogen storage disease, commonly referred to as type 2, in which glycogen accumulates across all kinds of muscle. Some patients die shortly after birth if the heart muscle is overloaded with too much by glycogen. Other patients have a milder heart disease and may survive to adolescence. Again, it was an incurable disease to ordinary doctors. And yet, Prof. Chen, is no ordinary doctor or scientist,

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and he took “Extraordinary Measures”. He invented a cure by infusing the missing enzyme to these patients. The intriguing story was even turned into a Hollywood movie with Harrison Ford playing scientist. Together, with the emergence of enzyme replacement for other genetic diseases, the decade around the turn of century is considered the Era of Enzyme Therapy. Around the same time, Prof. Chen developed methods to diagnose many of these genetic diseases at the time a baby is born so that those with diseases could be treated early and prevent child mortality. These methods became common practice and are now applied to the whole pouplation in US and other developed countries, in what is known as Newborn Screening.

After making two major discoveries, an ordinary scientist would be satisfied to rest and enjoy the fruits of one’s labours. During the past decade, however, technology advanced to the point where we can analyze a simplified but representative picture of our genetic makeup. For your information, our whole genetic code is made up of 3 x 10 ^9 bases (or digits of genetic information). Prof. Chen is keen to know which of the genetic codes cause people to have different responses to drug treatments. It is a field called pharmacogenetics. It is now accepted that our genetic codes influence how our body degrades or activates the drugs we receive, yet the ability to degrade or activate varies among the population, such that some people may experience toxic effects when given a standard safe dosage. Prof. Chen identified which genes cause differing responses in the population, and the modification of dosages and avoidance of certain drugs according to a patient’s genetic makeup are vital to improve patient case and safety. Once again, he played a leading role in the Era of Personalized Medicine.

Other than being an outstanding scientist, Prof. Chen has a kind heart. He has been repeatedly elected as one of the Best Doctors in America. He contributed to and supported the establishment of various non-governmental organizations related to the care of patients with genetic diseases in the US and Taiwan. Prof. Chen received numerous awards for his contributions to medical advances in genetic diseases. In recognition of his achievements, a Center that bears Chens’ name was established at Duke. He is also a generous donor and was named Philanthropist of the Year by Duke University. He and Mrs. Chen donate an annual Chen Award to the Human Genome Organisation to honor investigators who make significant contributions to the advancement of Human Genetics.

Nelson TangDepartment of Chemical PathologyLaboratory of Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong

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Pharmacogenomic study also identified an unusual form of granulysin secreted by these cytotoxic T lymphocytes and natural killer cells responsible for the rapid and disseminated keratinocyte death in SJS/TEN. The high sensitivity/specificity of genetic markers provides a plausible basis for developing tests to identify individuals at risk for drug hypersensitivity and indeed a large prospective study has shown that HLA-B*1502 screening before carbamazepine treatment can effectively reduce the incidence of CBZ-induced SJS/TEN. These translational researches demonstrated that preventing drug toxicity by screening people at risk before prescription of a drug is a clinical reality. Application of HLA-B*1502 genotyping as a screening tool for patient taking carbamazepine is now recommended by the Department of Health, Taiwan and by the US FDA.

Lecture Synopsis

Preventing Drug Toxicity with a Gene Test

Clinically observed drug toxicity so called adverse drug reactions (ADRs) account for 6-7 % of all hospital admissions and remain a major clinical problem. Pharmacogenomics aims to investigate the genetic basis of inter-individual differences in drug responses, such as efficacy, dose requirements, and adverse events. Research in pharmacogenomics has grown over the past decade, evolving from a candidate-gene approach to genome-wide association studies (GWAS). Genetic variants in genes coding for drug metabolism, drug transport, and more recently human-leukocyte antigens (HLA) have been linked to inter-individual differences in the risk of adverse drug reactions. I will use the following as an example to show that personalized medicine and pharmacogenomics is extremely useful in the right clinical settings.

Stevens-Johnson syndrome (SJS) and the related disease, toxic epidermal necrolysis (TEN), are two of the most serious ADRs. Carbamazepine (CBZ), used primarily in the treatment of epilepsy, neuralgia and bipolar disorder, is the commonest cause of SJS/TEN in Southeast Asian countries. We previously reported that CBZ-induced SJS/TEN in Chinese and many Southeast Asian populations are strongly associated with the human leukocyte antigen (HLA) B*1502. The strong genetic association suggests a direct involvement of HLA in the pathogenesis of drug hypersensitivity and indeed HLA molecule presents an antigenic drug and resulted in clonal expansion and activation of CD8+ cytotoxic T cells have been shown.

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development of this new drug has been adapted to a Hollywood

movie entitled “Extraordinary Measures” featured Harrison Ford

and Brendan Fraser. The story behind the scenes of the movie and

the challenges of new drug development will be discussed.

Lecture Synopsis

Challenges of New Drug Development: From Laboratory to Clinic to Hollywood

(Extraordinary Measures, The Story Behind the Scenes)

Pompe disease is an autosomal recessive disorder of glycogen

metabolism caused by a deficiency of the lysosomal enzyme

acid alpha-glucosidase (GAA). Patients present differentially with

variable rates of progression ranging from a rapidly progressive

course, often fatal by 1 year of age, to a slower, but nevertheless

relentlessly progressive course. Prior to 2006, therapy for Pompe

disease remained essentially palliative and the natural history

of infantile onset Pompe disease was uniformly poor with death

occurring usually by age 1 year from cardiomyopathy or respiratory

failure. Research on the development of enzyme replacement

therapy (ERT) started in the early 70’s but not until mid 90’s that

the in vivo efficacy of ERT was first demonstrated in the animal

model of Pompe disease. Subsequently, pilot human phase I/II

studies of recombinant human GAA began in 1999, followed by

phase II clinical trials and pivotal trials which eventually leads to

market approval of the Myozyme® (alglucosidase alfa, Genzyme,

Cambridge, MA, USA) in 2006 and more recently Lumizyme® in

2010 for late-onset patients. The story of a father searching for a

life-saving drug for his two children with Pompe disease and the

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Publications of Professor Chen, Yuan-Tsong

Hung, S.I., Chung, W.H. and Chen, Y.T.: Genetics of severe drug hypersensitivity reactions in Han Chinese. In: Pichler WJ (ed), Drug Hypersensitity, S. Karger AG, Switzerland, pp.105-114, 2007.

Kishnani, P.S., Decker-Phillips, M. and Chen, Y.T. Disorders of Carbohydrate Metabolism. In: Gleicher N. (Ed) Principles and Practices of Medical Therapy in Pregnancy, Appleton & Lange, Stamford, CT, 4rd edition, 2008.

Kishnani, P.S. and Chen, Y.-T.: Disorders of Carbohydrate Metabolism. In: Rudolph’s Pediatrics, 22nd edition, 2008.

Deeksha, B. and Chen, Y.-T.: Glycogen storage disease, type I Gene Reviews, 2008

Kishnani, P.S., Koeberl, D. and Chen, Y.-T.: Glycogen storage disease. In: Scriver C.R., Beaudet A.L.,Sly W.S.,Valle D. Online The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, Part 7, Charpter 71, 2009

Kishnani, P., Chen, Y.-T.: Defects in Metabolism of Carbohydrates. In: Behrman R.E., Kliegman R.M., and Jenson H.B. (eds) Nelson Textbook ofPediatrics, 19th Edition, Saunders Co. Philadelphia, 2009.

Chen, Y.-T. and Bali, Deeksha: Prenatal diagnosis of Disorders of Carbohydrate Metabolism. In: Genetic Disorders of the Fetus, Milunsky, A.and Milunsky J.M. (eds) Johns Hopkins University Press, Baltimore, 6th edition, pp. 554-576, 2010.

Bali, D.S., Chen, Y.-T., Goldstein, J. L.: Glycogen Storage Disease Type [in: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. December 2010.

Selected Publications of Professor Chen, Yuan-Tsong

Chen, Y.-T.: Disorders of Carbohydrate Metabolism. In: Rudolph’s Pediatrics, 21st Edition, 2003.

Chen, Y.-T.: Defects in Metabolism of Carbohydrates. In: Behrman R.E., Kliegman R.M., and Jenson H.B. (eds) Nelson Textbook of Pediatrics, 1st Edition, Saunders Co., 2003.

Chen, Y.-T.: Glycogen storage disease and other inherited disorders of carbohydrate metabolism. In: Harrison’s Principles of Internal Medicine, 16th Edition, 2003.

Chen, Y.-T.: Prenatal diagnosis of Disorders of Carbohydrate Metabolism. In: Genetic Disorders of the Fetus, Milunsky, A., ed. Johns Hopkins University Press, 5th edition. 2003.

Bali, D.S., Chen, Y.T.: glycogen storage disease. In: Encyclopedia of Diagnostic genomics and proteomics. 2005.

Ng, W.G., Chen, Y.T.: Disorders of carbohydrate metabolism. In Principles and Practice of Medical Genetics, Rimoin D ed. 5th edition, 2005.

Kishnani, P., Chen, Y.-T.: Defects in Metabolism of Carbohydrates. In: Behrman R.E., Kliegman R.M., and Jenson H.B. (eds) Nelson Textbook of Pediatrics, 18th Edition, Saunders Co., Philadelphia, pp. 601-616,2005.

Chen, Y.-T.: Glycogen storage disease and other inherited disorders of carbohydrate metabolism. In: Fauci AS, Braunwald E., Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J (eds) Harrison’s Principles of lnternal Medicine, 17th Edition, McGraw-Hill, New York, pp. 2757-2460, 2007.

Book Chapters (2002 to present)

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Published Original Refereed Journal Articles (2002 to present)

Matern, D., Bali, D., Seydewitz, H. J1., Chen, Y.-T.. Glycogen Storage Disease I: Diagnosis and genotype-phenotype correlation. Europ. J. Ped. 161: S10-19, 2002.

Ahearn, E.P., Speer, M.C., Chen, Y.-T., Sreffens, D.C., Cassidy, F., Van Meter, S., Provenzale JM, Weisler RH, Krishnan, K.R.R.. Investigation of Notch3 as a candidate gene for bipolar disorder using brain hyperintensities as an endophenotype. Amer. J Med. Genet. 114: 652-658, 2002.

Chen, Y.-T., Bali, D., and Sullivan, J.. Prenatal diagnosis in glycogen storage disease. Commentary. Prenatal Diagnosis. 5:537-539, 2002.

Joost, H.G., Bell, G.I., Best, J.D., Brinbaum, M.J., Chen, Y.T., Doege, H., James, D.E., Lodish, H.F., Moley, K.H., Moley, J.F., Mueckler, M., Rogers, S., Schumann, A., Seiro, S., Thorens, B.. Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators. Am J Physiol Endocrinol Metab.:E974-6, 2002.

Ding, E., Hu, H., Hodges, B.L., Migeon, F., Serra, D., Xu, F., Chen, Y.T., Amalfitano, A..Efficacy of Gene Therapy for a Prototypical Lysosomal Storage Disease (GSD-II) Is Critically Dependent on Vector Dose, Transgene Promoter, and the Tissues Targeted for Vector Transduction. Mol Ther. 5:436-46, 2002.

Beaty, R.M., Jackson, M., Peterson, D., Bird, A., Brown, T., Benjamin, D.K., Juopperi, T., Kishnani, P., Boney, A., Chen, Y.-T., Koeberl, D.O.. Delivery of glucose-6-phosphatase in a canine model for glycogen storage disease, type Ia, with adeno-associated virus (AAV) vectors. Gene Ther. 9:1015-1022, 2002.

Chou. J.Y., Matern, D., Mansfield, B.C., Chen, Y.T.. Type I Glycogen Storage Diseases: Disorders of the Glucose-6-Phosphatase Complex. Current Molecular Medicine. 2: 121-143, 2002.

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Chen, P., Hung, S.-I., Chen, S.-Y.and Chen, Y.T.: Allopurinol. In: Molecular and Translational Medicine, Pharmacogenomic Testing in Current Clinical Practice, Wu, A.H.B. and Yeo, K.-T. J. (eds) Humana Press, pp. 213-223, 2011.

Hung, S.-I., Chung, W.-H., Tsai, J.-J. and Chen, Y.T.: Carbamazepine and Its Structurally Related Antiepileptics. In: Molecular and Translational Medicine, Pharmacogenomic Testing in Current Clinical Practice, Wu, A.H.B. and Yeo, K.-T. J. (eds) Humana Press, pp. 225-236, 2011.

Lee, M.T.M., Chen, C.H., and Chen, Y.T.. Genomic medicine in Taiwan: research and developments. In: Genomics and Helth in the Developing World. Dhavendra Kumar(Ed) Oxford University Press, pp.874-885, 2012.

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Hunley, T.E., Corzo, D., Dudek, M., Kishnani, P., Amalfitano, A., Chen, Y.-T., Fogo, A.B., Tiller, G.E.. Nephrotic Syndrome Complicating a-Glucosidase Replacement Therapy for Pompe’s Disease. Pediatrics 114:e532-535, 2004.

Wu, J.W., Kao, H.J., Li, S.C., Stevens, R.D., Hillman, S., Millington, D.S., and Chen, Y.T.. ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease. J Clin Invest, 113:434-440, 2004.

Chung, W.H., Hung, S.I., Hong, H.S., Hsih, M.S., Yang, L.C., Ho, H.C., Wu, J.Y., Chen, Y.T.. A marker for Stevens-Johnson syndrome. Nature, 428: 486, 2004.

Quan, H., Athirakul, K., Westle, W.C., Torres, G.E., Stevens, R., Chen, Y.T., Coffman,T.M., Caron, M.G.. Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2. Molecular & Cellular Biology, 24: 4166-4173, 2004.

Xu, F., Ding, E., Liao, S.X., Migone, F., Dai, J., Schneider, A., Serra, D., Chen, Y.T., Amalfitano, A.. Improved efficacy of gene therapy approaches for Pompe disease using a new, immune-deficient GSD-11 mouse model. Gene Ther. Nov;1 1 (21 ): 1590-8, 2004.

Hwu, W.L., Yang, C.F., Fann, Cathy S.J., Chen, C.L., Tsai, T.F., Chien, Y.H., Chiang, S.C., Chen, C.H., Hung, S.I., Wu, J.Y., and Chen, Y.T.. Mapping of psoriasis to 17q terminus.J Medical Genetics, 42:152-158, 2005.

Xu, F., Ding, E., Migone, F., Serra, D., Schneider, A., Chen, Y.T., Amalfitano, A..Glycogen storage in multiple muscles of old GSD-II mice can be rapidly cleared after a single intravenous injection with a modified adenoviral vector expressing hGAA. J Gene Med 7: 171-178, 2005.

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Shen, J.J., Chen, Y.T. Molecular Characterization of Glycogen Storage Disease Type III.Current Molecular Medicine 2: 167-175, 2002.

Sun, B.D., Chen, Y.-T., Bird, A., Xu, F., Hou, Y.-X., Amalfitano, A., and Koeberl, D.O.. Packaging of an AAV vector encoding human acid a-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-adena-associated virus vector. Mol Ther 7:467-477, 2003.

Koeberl, D.O., Young, S.P., Gregersen, N., Vockley, J., Smith, W.E., Weavil, S., Chaing, S., McDonald, M.T., Kishnani, P.S., Chen, Y.T., and Millington, D.S.. Rare defects of metabolism with elevated butyryl-carnitines detected by tandem mass spectroscopy newborn screening. Pediatr Res 54:219-23, 2003.

Wylie, A.A., Pulford, D.J., McVie-Wylie, A.J., Waterland, R.A., Evans, I-I.K., Chen, Y.-T., Nolan, C.M., Orton, T.C., Jirtle, R.L.. Tissue-specific Inactivation of Murine M6P/IGF2R. Amer J Pathology, 162:321-8, 2003.

McVie-Wylie,A.J., Ding, E.Y., Lawson, T., Serra, D., Migone, F.K., Pressley, D., Mizutani, M., Kikuchin, T., Chen, Y.-T., Amalfitano, A.. Multiple muscles in the AMD quail can be “cross-corrected” of pathologic glycogen accumulation after intravenous injection of an [E1-, polymerase-] adenovirus vector encoding human acid- a glucosidase. J. Gene Med. 5:399-406, 2003.

Sun, B.D., Chen, Y.-T., Bird, A., Amalfitano, A., Koeberl, D.O.. Long-term correction of glycogen storage disease type II with a hybrid adenovirus-adena- associated virus vector. Mol Ther 7:193-201, 2003.

Young, S.P., Stevens, R.D., An, Y., Chen, Y.T., Millington, D.S.. Analysis of a glucose tetrasaccharide elevated in Pompe disease by stable isotope dilution-electrospray ionization tandem mass spectrometry. Anal Biochem 316: 175-180, 2003.

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Liu, Y.F., Chen, W.M., Lin, Y.F., Yang, R.C., Lin, M.W., Li, L.I-I., Chang, Y.H., Jou, Y.S., Lin, P.Y., Su, J.S., Huang, S.F., Hsiao, K.J., Fann, C.J.S., Hwang, H.W., Chen, Y.T., Tsai, S.F.. Type II Collagen Gene Variants and Inherited Osteonecrosis of the Femoral Head. New Eng! J Med 352: 2294-2301, 2005.

Franco, L.M., Sun, B., Yang, X., Bird, A., Zhang, H., Schneider, A., Brown, T., Young, S.P., Clay, T.M., Amalfitano, A., Chen, Y.T., Koeberl, D.D.. Evasion of Immune Responses to Introduced Human Acid alpha-Glucosidase by Liver-Restricted Expression in Glycogen Storage Disease Type II. Mol Ther 12(5):876-84, 2005.

Hung, S.I., Chung, W.H., Chen, Y.T.. HLA-B genotyping to detect carbamazepine induced Stevens-Johnson syndrome: implications for personalizing medicine. Invited review Personalized Medicine, 2:225-237, 2005.

Das, B. B., Narkewicz, M.R., Sokol, R.J ., Chen, Y.T., Bali, D., Li, S.C., Matthews, M.R., Mierau, G.W., Uvy, D. D.. Amylopectinosis disease isolated to the heart with normal glycogen branching enzyme activity and gene sequence. Pediatric Transplantation, 9: 261-265, 2005.

Hung, S.I., Chung, W.H., Jee, S.H., Chen, W.C., Chang, Y.T., Lee, W.R., Hu, S.L., Wu, M.T., Chen, G.S., Wong, T.W., I1siao, P.F., Chen, W.H., Shih, H.Y., Fan, W.H., Wei, C.Y., Lou, Y.H., Huang, Y.L., Lin, J.J., Chen, Y.T.. Genetic susceptibility to carbamazepine induced cutaneous adverse drug reactions. Pharmacogenetics and Genomics, 16:297-306, 2006.

Lin, W.I-l., Chuang, L.M., Chen, C.H., Yeh, J.I., Hsieh, P.S., Cheng, C.H., Chen, Y.T.. Association study of genetic polymorph isms of SLC2Al 0 gene and type 2 diabetes in Taiwanese population. Diabetologia, 49: 1214-21, 2006.

Pan, W.H., Fann, C.J.S., Wu, J.Y., Hung, Y.T., Ho, M.S., Ta, T.H., Chen, Y.J., Liao, C.J., Yang, M.L., Cheng, A.T.A., Chen, Y.T.. Han Chinese Cell and Genome bank in Taiwan: purpose, design and ethical considerations. Human Heredity, 61: 27-30, 2006.

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Hwang, H.W., Niu, D.M., Hwang, B.T., Chen, J.J., Lin, Y.J., Shieh, R.C., Lee M.T., Hung, S.I., Wu, J.Y., Chen, Y.T.. R1193Q of SCN5A, a Brugada and long QT mutation, is a common polymorphism in Han Chinese. J Med Genet 42:e7, 2005.

Sun, Baodong, Zhang, Haoyue, Franco, Luis M., Young, Sarah P., Schneider, Any, Bird, Andrew, Amalfitano, Andrea, Chen, Y. T. and Koeberl, Dwight D.. Efficacy of an Adeno-associated Virus 8-Pseudotyped Vector in Glycogen Storage Disease Type II. Mol Ther 1 1(1):57-65, 2005.

Franco, L., Krishnamurthy, V., Weinstein, D., Arn, P., Clary, B., Chen, Y.T., Kishnani, P. S.. Hepatocellular Carcinoma in Glycogen Storage Disease type I. Journal oflnherited Metabolic Disease, 28: 153-162, 2005.

Hung, S.-I., Chung, W.-H., Liou, L.-B., Chu, C.-C., Lin, M., Huang, H.-P., Lin, Y.-L., Lan, J.-L., Yang, L.-C., Hong, H.-S., Chen, M.-J., Lai, P.-C., Wu, M.-S., Chu, C.-Y., Wang, K. H., Chen, C.-H., Fann, C.S.J., Wu, J.-Y., Chen, Y.-T.. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci, 102 (11): 4134-9, 2005.

An, Y., Young, S., Kishnani, P.S., Millington, D.S., Amalfitano, A., Corzo, D., Chen, Y.T.. Glucose Tetrasaccharide as a Biomarker for Monitoring Therapeutic Responses to Enzyme Therapy of Pompe Disease. Mol. Genet. Metabolism,; 85(4):24 7-54, 2005.

Yuan, I-I.Y., Chen, J.J., Lee, M.T. Michel, Chen, Y.F., Charng, M.J., Lu, M.J., Hung, C.R., Wei, C.Y., Chen, C.H., Wu, Y.J., Chen, Y.T.. A novel functional VKORC I promoter polymorphysm is associated with inter-individual and inter-ethnic differences in wafarin sensitivity. Human Molecular Genetics, 14: 1745-1751, 2005.

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Niu, D.M., Hwang, B.T., Hwang, H.W., Wang, N.H., Wu, J.Y., Lee, P.C., Chien, J.C., Shieh, R.C., Chen, Y.T.. A common SCN5A polymorphism attenuates a severe cardiac phenotype caused by a nonsense SCN5A mutation in a Chinese family with an inherited cardiac conduction defect. J Med. Genet. 43: 817-821, 2006

Li, L.H., Ho, S.F., Chen, C.H., Wei, C.Y., Li, L.Y., Hung, S.l., Chung, W.H., Pan, W.H., Wong, W.C., Lee, M.T.M., Wu, J.Y., Chen, Y.T.. Long contiguous stretches of homozygosity in the Human Genome, Human Mutation, 27:1115-21, 2006.

Yuan, H.U., Chiou, J.J., Tseng, W.H., Liu, C.H., Liu, C.K., Lin, YJ., Wang, H.H., Yao, A., Chen, Y.T., Hsu, C.N .. FASTSNP: An always up-to-date and extendable service for SNP function analysis and prioritization. Nucleic Acid Res, 34: W635-41, 2006.

Yang, H.C., Liang, YJ., Huang, M.C., Li, L.H., Lin, C.H., Wu, J.Y., Chen, Y.T., Fann, C.S..A genome-wide study of preferential amplification/ hybridization in microarray-based pooled DNA experiments. Nucleic Acids Res. 34: e I 06, 2006.

Koeberl, D.O., Sun, B.D., Damodaran, T.V., Brown, T., Millington, D.S., Benjamin, O.K. Jr, Bird, A., Schneider, A., Hillman, S., Jackson, M., Beaty, R.M., Chen, Y.T. Early, sustained efficacy of adena-associated viurs vector-mediated gene therapy in glycogen storage disease type Ia. Gene Ther. Sep; 13(17):1281-9, 2006.

Sun, B., Zhang, H., Benjamin, O.K. Jr, Brown, T., Bird, A., Young, S.P., McVie-Wylie, A., Chen, Y.T., Koeberl, D.O.. Enhanced Efficacy of an AAV Vector Encoding Chimeric, Highly Secreted Acid alpha-Glucosidase in Glycogen Storage Disease Type II. Mol Ther 14(6):822-30, 2006.

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Yang, H.C., Lin, C.H., Hsu, C.L., Hung, S.I., Wu, J.Y., Pan, W.H., Chen, Y.T., Fann, C.S. A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians. J Biomed Sci. 13:489-498, 2006.

Ansong, A., Li, J.S., Nozik-Grayck, E., Ing, R., Kravitz, R., fdriss, S.I., Kanter, R.J., Rice, H., Chen, Y.T., Kishnani, P.S.. Electrocardiographic response to enzyme replacement therapy for Pompe disease. Genet Med. May;8(5):297-301, 2006.

Cook, A.L., Kishnani, P.S., Carboni, M.P., Kanter, R.J., Chen, Y.T., Ansong, A.K., Kravitz, R.M., Rice, H., Li, J.S.. Ambulatory Electrocardiogram Analysis in Infants Treated with Recombinant Human Acid Alpha Glucosidase (GAA) Enzyme Replacement Therapy for Pompe Disease. Genet Med. 8(5):313-7, 2006.

Zhang, H., Kallwass, H., Young, S.P., Carr, C., Dai, J., Kishnani, P.S., Millington, D.S., Keutzer, J., Chen, Y.T., Bali, D.. A comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid a-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet Med. May;8(5):302-6, 2006.

Kishnani, P.S., Nicolino, M., Voit, T., Rogers, R.C., Tsai, A.C., Waterson, J., Herman, G.E., Amalfitano, A., Thurberg, B., Richards, S., Davison, M., Corzo, D., Chen, Y.T.. Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. J Pediatr 149(1): 89-97, 2006.

Burrow, T.A., Hopkin, R.J., Bove, K.E., Miles, L., Wong, B.L., Chaudhary, A., Bali, D.,Li, S.C., Chen, Y.T.. Non-lethal congenital hypotonia due to glycogen storage disease type IV.Am J Med Genet 140:878-82, 2006.

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Distinguished Visiting Scholars from 1981 to 2012

Year Name and Institution (Discipline)

Jan 1982 Professor C.N. YANG 楊振寧教授

State University of New York (Physics)

Apr 1982 Professor Stuart SCHRAM 宣道華教授

University of London (History)

Jan 1983 Professor Ezra VOGEL 傅高義教授

Harvard University (Sociology)

Dec 1985 Professor Samuel FINER 范乃三教授

Oxford University (Political Science)

Apr 1985 Professor Peng-yuan CHANG 張朋園教授

National Taiwan Normal University (History)

Mar 1986 Professor Lawrence J. LAU 劉遵義教授

Stanford University (Economics)

Sep 1986 Professor K.C. CHANG 張光直教授

Harvard University (Archaeology)


Nov 1986 Professor Shing-shen CHERN 陳省身教授

Nankai University (Mathematics)

Nov 1986 Dr. Franklin CHANG-DIAZ 張福林博士

NASA Plasma Fusion Center (Space Science)

Jan 1988 Professor Norton GINSBURG 金斯伯教授

East-West Center (Geography)

Nov 1988 Professor Robin M. NORRIS 羅理思教授

University of Auckland (Medicine)

Apr 1989 Professor Ky FAN 樊璣教授

University of California, Santa Barbara (Mathematics)

Nov 1989 Professor Jan. SVARTVIK 史華域教授

Lund University (English Language)

Nov 1990 Professor Wlodzimierz BRUS 布魯斯教授

Oxford University (Social Economics)

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Oct 1991 Professor B. SCHLESINGER 施樂生教授

University of Toronto (Social Work)

Mar 1992 Professor Jonathan SPENCE 史景遷教授

Yale University (History)

Feb 1993 Professor Kwang-chung YU 余光中教授

National Sun Yat-sen University (Chinese Language)

Apr 1993 Professor Richard PORTES 潘迪思教授 University of London (Economics)

Nov 1993 Professor Sidney GREENBAUM 郭思言教授

University London College (English Language)

Mar 1994 Professor Janos KORNAI 康乃爾教授 Harvard University (Finance)

Nov 1994 Professor Feng-sheng HE 何鳳生教授 Institute of Occupational Medicine (Medicine)

Mar 1995 Professor James CAHILL 高居翰教授 University of California (Art History)



Nov 1995 Professor Graham FISHBURNE 費伯恩教授 University of Alberta (Education)

Mar 1996 Professor Shupeng CHEN 陳述澎教授 Institute of Remote Sensing Applications Chinese Academy of Science (Science)

Oct 1996 Professor Chia-ying YEH 葉嘉瑩教授 University of British Columbia (Asian Studies)

Nov 1996 Dr. Leroy CHIAO 焦立中博士 NASA Space Center (Space Science)

Mar 1997 Professor Gillian BROWN 鮑姬蓮教授

Cambridge University (English Language)

Dec 1997 Dr. David Da-i HO 何大一博士

Aaron Diamond AIDS Research Center (Medicine)

Mar 1998 Professor John W. REPS 韋約翰教授

Cornell University (City Planning)

Oct 1998 Professor Marilyn S. ALBERT 艾美蓮教授

Harvard Medical School (Psychology)

40 41



Mar 1999 Professor Harry HARDING 何漢理教授

The George Washington University (Political Science) Nov 1999 Professor Janice MORSE 莫珍寧教授

University of Alberta (Nursing)

Feb 2000 Professor Arthur ELLIS 艾禮詩教授

University of Wisconsin-Madison (Material Science)

Nov 2000 Professor Kenneth DODGE 杜甘夫教授

Duke University (Educational Psychology)

Mar 2001 Professor Paul VANHOUTTE 尹浩德教授

Institut de Recherches Internationale Server (Medicine)

Nov 2001 Professor M. F. HAWTHORNE 霍桑教授

University of California, Los Angeles (Chemistry)

Mar 2002 Professor Richard ESTES 倪思迪教授

University of Pennsylvania (Social Work)

Nov 2002 Professor Tony F. CHAN 陳繁昌教授

University of California, Los Angeles (Mathematics)


Mar 2003 Professor Yuan T. LEE 李遠哲教授

Academia Sinica, Taiwan (Chemistry)

Mar 2004 Professor Zhi-an DONG 董治安教授

Shandong University (Chinese Language)

Mar 2004 Professor Zeng-yi QIAN 錢曾怡教授

Shandong University (Chinese Language)

Oct 2004 Professor Yuk-ling YUNG 翁玉林教授

California Institute of Technology (Planetary Science)

Feb 2005 Professor Michael C. CORBALLIS 郭敏豪教授

University of Auckland (Psychology)

Nov 2005 Professor Stanley N. COHEN 柯恩教授

Stanford University (Medicine)

Mar 2006 Professor Peter C. ORDESHOOK 歐德修教授

California Institute of Technology (Political Science)

Oct 2006 Professor F. Sherwood ROWLAND 羅蘭德教授

University of California, Irvine (Chemistry and Earth System Science)

42 43



Mar 2007 Professor YUAN Longping 袁隆平教授

China National Hybrid Rice R&D Center (Biology)

Nov 2007 Professor ZHANG Yaping 張亞平教授

Kunming Institute of Zoology, CAS (Zoology)

Oct 2008 Professor QIN Dahe 秦大河教授

State Key Laboratory of Cryoshperic Sciences (Meteorology)

Oct 2010 Professor Kay DEAUX 杜爾琦教授

The City University of New York (Pscyhology)

Oct 2010 Professor Sam GLUCKSBERG 郭保山教授

Princeton University (Psychology)

Oct 2011 Professor Herman S. CHEUNG 張醒鐘教授

University of Miami (Medicine)

Oct 2012 Professor CHEN Yuan-Tsong 陳垣崇教授

Academia Sinica, Taiwan (Medicine)

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Mission of the College

In elaborating the College motto “Make One’s Virtues Shine and Renew the People”, United College strives to serve the people of Hong Kong and China and the world through integrative education, pastoral care as well as moral and spiritual enhancement of the young.

professor chen yuan-tsong 陳垣崇 academia sinica, taiwan

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