Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

The overall objectives of our laboratory areto discover key genes and molecularmechanisms for human disease. Areas ofinterest include cardiacdisease, vascular malformations,eye disease, andneurological disorders.Cardiac arrhythmiascause >300,000 suddendeaths each year in the UnitedStates alone. We havepioneered the field of thegenetic studies of cardiacarrhythmias includingidiopathic ventricularfibrillation (IVF) and long QTsyndrome (LQT). We havecloned three genes for LQTand discovered the first genefor IVF. We continue to findnew arrhythmia genes, andperform genotype-phenotypecorrelation studies. Furthermore,we have created amouse model for LQT,ventricular tachycardia/ventricular fibrillation/sudden cardiac death by targeting a human LQTgene. Continueing characterization of this mousemodel as well as biochemical dissection of LQTgenes will reveal fundamental molecularmechanisms for pathogenesis of lethalarrhythmias.The second major project in our laboratoryis to clone a new gene for congenital heart diseaseThe Department of Molecular CardiologyGenetics and Molecular Biologyof Human DiseaseQing Wang, Ph.D.,M.B.A.Director, Center forCardiovascular Genetics(CHD), which is the most common birth defect.We are also using biochemical and cell biologicaltools to functionally characterize TBX5 andNKX2.5, two key genesinvolved on cardiacdevelopment and CHD.The third major areaof our research is on vascularbiology (vasculogenesis andangiogenesis). By studyingKlippel-Trenaunay syndrome,a congenital vascular disease,we have identified two genesinvolved in vascularmorphogenesis. Furtherstudies of these genes willlead to significant insightinto molecular mechanismsunderlying vasculogenesisand angiogenesis.The fourth project ison genetics of coronaryartery disease (CAD) andmyocardial infarction (MI),the No. 1 killer disease in theUnited States and otherdeveloped countries. By linkage analysis, we haveestablished six genetic loci for CAD and MI.Ongoing positional cloning will lead to theidentification or cloning of major genes for CADand MI.Finally, our laboratory is using linkageanalysis and positional cloning to identify genesfor retinitis pigmentosa, restless legs syndrome,and epilepsy.Chen, Q., Kirsch, G., Zhang, D., Brugada, R., Brugada, J., Brugada, P., Potenza, D., Moya, A., Borggrefe, M.,Breithardt, G., Oritz-Lopez, R., Wang, Z., Anzalevitch, C., O’Brien, R.E., Schultz-Bahr, E., Keating, M.T., Towbin,J.A., and Q. Wang (1998) Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature392:293-296.Wang, Q., Timur, A., Szafranski, P., Sadgephour, A., Jurecic, V., Cowell, J., Baldini, A., and D.J. Driscoll(2001) Identification and molecular characterization of de novo translocation t(8;14)(q22.3;q13) associated with avascular and tissue overgrowth syndrome. Cytogenet. Cellular Genet. 95:183-188.Chen, S., Chung, M. K., Martin, D., Rozich, R., Tchou, T.J., and Q. Wang (2002) SNP S1103Y in the cardiacsodium channel gene SCN5A is associated with cardiac arrhythmias and sudden death in a Caucasian family. J.Med. Genet. 39:913-915.Wu, L., Nishiyama, K., Hollyfield, J.G., and Q. Wang (2002) Localization of Na v1.5 sodium channel protein inthe mouse brain. Neuroreport 13:2547-2551.Fan, C., Duhagon, M. A., Oberti, C., Chen, S., Hiroi, Y., Komuro, I., Duhagon, P.I., Canessa, R., and Q. Wang(2002) Novel TBX5 mutations and molecular mechanism for Holt-Oram syndrome. J. Med. Genet. 40:E29.Wang, Q., Gu, Y., Ferguson, J.M., Chen, Q., Boatwright, S., Gardiner, J., Below, C., Espinosa, J., Nelson, D.L.,and L.G. Shaffer (2003) Cytogenetic analysis of obsessive-compulsive disorder (OCD): Identification of aFRAXE fragile site. Am. J. Med. Genet. 118A:25-28.THE Q. WANGLABORATORYPROJECT SCIENTISTShaoqi Rao, Ph.D.RESEARCH ASSOCIATESRajkumar Kadaba, Ph.D.Carlos Oberti, M.D.Gong-Qing Shen, M.D., Ph.D.RESEARCH FELLOWSShenghan Chen, M.D.Lejin Wang, M.D.POSTDOCTORAL FELLOWSChun Fan, M.D., Ph.D.Xiaoli Tian, Ph.D.Anyle Anil Timur, Ph.D.Sandro Yong, Ph.D.Sun-Ah You, Ph.D.Lin Li, Ph.D.NEUROLOGY FELLOWJocelyn Bautista, M.D.RESEARCH TECHNICIANZhaohui Tang, B.S.GRADUATE STUDENTSSteve Archaki, M.D.Wei Du, B.S.Mugen Liu, M.S.Ling Wu, M.S.STUDENTSGenise Owens, B.S. 1Josephine Williams 21Cuyahoga CommunityCollege, Cleveland, OH2John Hay High School-CCF/NIH/HHMI Training ProgramCOLLABORATORSMina K. Chung, Ph.D. 1David J. Driscoll, Ph.D. 2William G. Ondo, M.D. 3Patrick J. Tchou, Ph.D. 1Eric J. Topol, M.D. 11Dept. of CardiovascularMedicine, CCF2Dept. of Pediatrics, MayoMedical School, Rochester, MN3Baylor Coll. of Med., Houston,TX131