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550 APBN • Vol. 3 • No. 22 • 1999
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Dr. Lap-Chee Tsui
OUTSTANDING SCIENTIST
r. Lap-Chee Tsui is
Geneticist-in-Chief and Head ofthe Genetics and Genomic BiologyProgram of the Research Institute at theHospital for Sick Children in Toronto,Canada. He is cross-appointed asProfessor in the Department ofMolecular and Medical Genetics andInstitute of Medical Science at theUniversity of Toronto, where he alsoholds the title of H.E. Sellers Chair inCystic Fibrosis and UniversityProfessor.
Dr. Tsui was born in Shanghai, raisedand educated in Hong Kong. Heobtained his bachelor and masterdegrees from the Chinese Universityof Hong Kong. In 1979, he receivedhis doctoral degree (Ph.D.) from the
University of Pittsburgh, where histhesis was on the structure andmorphogenesis of a bacteriophagelambda as a model to study somebasic mechanisms in life processes.After training briefly in the BiologyDivision of Oak Ridge NationalLaboratory on the biology if RNAtumor virus, he joined the Departmentof Genetics at The Hospital forSick Children to work on cystic fibrosis(CF), a frequently fatal inheriteddisorder that affects about 1 in 2500Caucasian children in the world.
In 1985, together with Dr. ManuelBuchwald and scientists at Colla-borative Research Inc. he identify thefirst DNA marker linked to CF onchromosome 7. Four years later,Dr. Tsui, together with Drs. JackRiordan and Francis Collins, led ateam of researchers at the Toronto’sHospital for Sick Children andUniversity of Michigan, respectively,to “a major breakthrough in humangenetics” by isolating the defectivegene responsible for CF and definingthe principal mutation (F508).The work was described in threeseminal papers in the 8 September 1989issue of Science (see Table 1); thegene was called the Cystic FibrosisTransmembrane Regulator (CFTR).The much celebrated announcementcame after seven years of meticulous andlaborious hard work in his laboratory.Dr. Tsui’s achievement was named inthe Science magazine as “the mostrefreshing scientific development of1989” and hailed in Maclean’s HonorRoll as “discoveries of hope at the heartof human life” in the same year. Dr.Tsui’s work was funded by grants fromthe Canadian Cystic Fibrosis Foundation,and, the Cystic Fibrosis Foundation andthe National Institutes of Healthin the US.
The current research in Dr. Tsui’slaboratory is directed towards a betterunderstanding of CF. His majorresearch interests in CF have focussedon the detection of additionalmutations in the gene, correlation ofgenotype with phenotype, promoteranalysis of CFTR, the generation ofmouse models of the disease, and thestudy of modifier genes that canmodulate the severity of CF disease.These studies will bring additionalinsights into the pathogenesis of CFand alternative means of therapy forthe disease. Dr. Tsui has alsoorganized a worldwide consortium forCF mutation analysis. The work hasresulted so far in the description ofover 850 different CFTR mutations,providing information for the structureand function analysis of the CFTRprotein. The success of thisconsortium, the first of its kind, hasnow been used as a model for manystudies of genetic disease.
Dr. Tsui is also active in other geneticand disease gene analysis. He hasrecently obtained funding from
D
In 1989, Dr. Tsui,together with
Drs. Jack Riordan andFrancis Collins, led
a team of researchers atthe Toronto’s Hospitalfor Sick Children and
University of Michigan,respectively, to
“a major breakthroughin human genetics”
by isolatingthe defective
gene responsible forCF and defining
the principal mutation(F508).
Dr. Lap-Chee Tsui
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551APBN • Vol. 3 • No. 22 • 1999
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the Canadian Genome Analysisand Technology Program to performa physical mapping study ofchromosome 7. The goal of this projectis to generate an integrated genetic,physical and transcriptional mapfor this chromosome to facilitateidentification of other disease genes.He is collaborating with over 20laboratories around the world in thelatter endeavor. His laboratory iscurrently trying to identify the genesthat contribute to Williams syndrome(a multisystematic disorder affectingprimari ly cognit ive funct ion inchildren) and a genetic disorder thataffects limb development. Dr. Tsuiis a key member of the CanadianGenetic Disease Network, which is
OUTSTANDING SCIENTIST
Rommens J M, Iannuzzi M C, Kerem B, Durmm M L, Melmer G, Dean M, Rozmahel R, Cole J L, Kennedy D,Hidaka N, Zsiga M, Buchwald M, Riordan J R, Tsui L-C and Collins F S, Identification of the cystic fibrosis gene:chromosome walking and jumping, Science 245: 1059 − 1065 (1989).
Riordan J R, Rommens J M, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N,Chou J-L, Drumm M L, Iannuzzi M C, Colin F S and Tsui L-C, Identification of the cystic fibrosis gene: cloningand characterization of complementary DNA, Science 245: 1066 − 1073 (1989).
Kerem B, Rommens J M, Buchanan J A, Markiewicz D, Cox T K, Chakravarti A, Buchwald M and Tsui L - C,Identification of the cystic fibrosis gene: genetic analysis, Science 245: 1073 − 1080 (1989).
Rozmahel R, Wilschanski M, Matin A, Plyte S, Oliver M, Auerbach W, Moore A, Forstner J, Durie P, Nadeau J,Bear C E and Tsui L-C, Modulation of disease severity in CF mice by a secondary genetic factor, Nature Genet.
12: 280 − 287 (1996).
Crackower M A, Motoyama J and Tsui L-C, Defect in the maintenance of the apical ectodermal ridge in theDactylaplasia mouse, Devel. Biol. 201: 78 − 89 (1998).
Osborne, R L, Campbell T, Daradich A, Scherer S W and Tsui L-C, Identification of a putative transcription factorgene (WBSCR11) that is commonly deleted in Williams-Beuren syndrome, Genomics 57:279 − 284 (1999).
Zielenski J, Corey M, Rozmahel R, Markiewicz D, Aznarez I, Casals T, Larriba S, Mercier B, Cutting G,Macek M, Palacio A, Langfelder E, Henshaw C, Marshall B, DeCelie-Germana, Calustres M, Nowakowska A,Bal J, Ferec C, Estivill X, Durie P and Tsui L-C, Detection of a cystic fibrosis modifier (CFM1) locus for meconiumileus on chromosome 19q13, Nature Genet. 22: 128 − 129 (1999).
part of the Federal Government topromote the transfer of researchfindings to commercial applications.He is also currently Chair of theCanadian Genome Research (GenomeCanada) Task Force to initiate a newvision for Canada’s future inbiotechnology and health.
In between travelling worldwideto give lectures to medical doctors,scientists and students, Dr. Tsuidevotes most of his spare timein volunteer work in the Chinesecommunity. He enjoys good foodand wine.
Dr. Tsui’s honors include the tiles ofSenior Scientist of the MedicalResearch Council of Canada, Fellow
of the Royal society of Canada,Fellow of the Royal Society ofLondon and Member of AcademiaSinica. In addition to many nationaland international prizes, Dr. Tsuireceived honorary doctoral degreesfrom University of King’s College(Doctor of Civil Law, honoris causa),University of New Brunswick(Doctor of Science, honoris causa),the Chinese University of Hong Kong(Doctor of Science, honoris causa)and St. Francis Xavier University(Doctor of Letters, honoris causa).He also received the Order of Canada(Officer rank) in 1991. He haspublished 300 scientific papers.
Table 1: Selected Publications
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