李端祥+Li-DCMgenetics_HunanConference2014.pptVIP

Figure 1. A large DCM pedigree carrying TNNT2 R141 mutation Li D et al. Circulation. 2001;104:2188-2193 Novel cardiac?troponin?T mutation R141W cause DCM Genetics helps mechanistic insights_ TNNT2 mutation R141W stabilizes the troponin T–tropomyosin interaction and causes a Ca2+?desensitization Effects of R141W and R94L mutations in cTnT on force generation of cardiac muscle. Effects of DCM- and HCM-causing mutations in cTnT on the affinity for α-tropomyosin. Lu QW., et al. JMCC 2003; 35:1421 Protective action of tetramethylpyrazine phosphate against dilated cardiomyopathy in cTnT(R141W) transgenic mice ?Zhao HP., et al., Acta Pharmacologica Sinica (2010) 31: 281–288 Allele-Specific Silencing of Mutant Myh6 Transcripts in Mice Suppresses Hypertrophic Cardiomyopathy Jiang J. et al., Science 2013; 342:111 Genetics Discovery Make Disease Gene-targeted Molecular Therapy Possible Cardiovascular Genetics The principal role of the cardiologist will change from recognizing and managing established disease, as is the case today, to interpreting and applying genetic information in prevention and treatment in 2020 and beyond. Eugene Braunwald, MD Simon Dack Lecture American College of Cardiology 2003 JACC 2003;42:2031-41 Acknowledgements Case Western Reserve U Huazhong U of Science Technology Qing K Wang, PhD (also) Yan Xu, PhD Chunyan Luo, PhD Ping Ouyang, PhD Ottawa Heart Institute Robert Roberts, MD All participating patients family members All referring physicians NHLBI grant supports FHRI grant supports Welcome contacting collaboration: duanxli@ DCM Labtoratory at Uiversity of Miami OSU Davis Dorothy Heart Institute Ray Hershberger, MD Nadine Norton, PhD Jorge Gonzalez, BS Jason Cowan, MS Ana Moral, MS, CGC Dale Hedge, PhD Jill Siegfried, MS, CGC U of Miami Collaborators Eden Martin, PhD Evadnie Rampersand, PhD Stephan Zuchner, MD Steve Mangos, PhD Gennaro D’Urso, PhD David Wiley, PhD U of Washington Genome Sciences Mark J. Rieder,