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Xiaoping Lin Tongji university Johns Hopkins University.

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Presentation on theme: "Xiaoping Lin Tongji university Johns Hopkins University."— Presentation transcript:

1 Xiaoping Lin Tongji university Johns Hopkins University

2 Johns Hopkins, the Quaker merchant, banker and businessman, left $7 million in 1873 to create The Johns Hopkins University and The Johns Hopkins Hospital Introduction-JHMI

3  Over $6.5 billion in operating revenues  More than 34,000 combined full-time equivalent employees; among largest private employers in Maryland  Annual outpatient visits: over 2.6 million  Annual Emergency Department visits: over 294,000  Annual hospital admissions: over 114,000  Annually ranked #1 in NIH funding for U.S. medical schools ($439 million)  Medical and doctoral students: over 1,400  Full-time faculty: over 2,550  Part-time faculty: over 1,290 Johns Hopkins Medicine (2012 projected)

4 The Johns Hopkins Johns Hopkins Children’s Center Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Bayview Medical Center All Children's Hospital (St. Petersburg, FL) Howard County General Hospital (Columbia, MD) Sibley Memorial Hospital (Northwest Washington D.C.) Suburban Hospital (Bethesda, MD)

5 Achievements Pioneered surgery for breast cancer (1889) First major medical school in the United States to admit women (1893) First to develop renal dialysis (1912) First direct heart surgery (blue baby operation,1944) u Developed cardiopulmonary resuscitation – CPR (1958) Invented first implantable, rechargeable pacemaker for cardiac disorders (1972) Pioneered complex surgeries for separating twins joined at the head (1987) Among the first to isolate and cultivate human embryonic stem cells (1998) Discovered that in-vitro fertilization (IVF) appears to be associated with a rare combination of birth defects characterized by excessive growth of various tissues (2002) Developed the first biologic pacemaker for the heart, paving the way for a genetically engineered alternative to implanted electronic pacemakers (2002)

6 “Telomere” Expert Carol Greider Shares 2009 Nobel Prize in Physiology or Medicine “Aquaporin Protein” Expert Peter C. Agre Shares 2003 Nobel Prize in Chemistry

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9 Echo Nurses & Sonographers Grap/ Access Team Referring

10 HCM Clinic EchoSurgeryGeneticsEPPEDSCMR/CTNuclear Clinical Research

11  52 M  Hx of long standing hypertension  Occasional episodes of dizziness  Single syncopal episode while standing  44 M  Competitive cyclist  Borderline hypertension  Worsening fatigue; exertional dyspnea x 2 years  Echo – severe ventricular hypertrophy

12  Physiologic hypertrophy – Athlete’s Heart  Hypertension related hypertrophy  Hypertrophic cardiomyopathy  Infiltrative cardiomyopathy  Cardiac amyloid

13  Inherited cardiomyopathy  Mutation in genes encoding sarcomeric proteins  Diverse clinical presentation  Common (1:500) Spirito: NEJM, 1999

14  Hypertrophy (>1.5 cm)  Any distribution ▪ Concentric vs. asymmetric ▪ Basal vs. mid vs. apical vs. diffuse  Severity ▪ Normal to severe ▪ (6.0 cm- largest reported)  Systolic anterior motion of mitral valve  Outflow tract gradient  Present vs. absent  Rest vs. provocation  Day to day variation Ommen, Circ, 2003

15 Challenges: 1.Distinguish HCM from other causes of hypertrophy (hypertensive heart disease, athlete’s heart) 2.Risk stratification of sudden death 3.Preclinical diagnosis Needed: Non-invasive diagnostic tools (EP, imaging, genomic, proteomic computational) to reliably diagnose HCM and distinguish it from other pathologies

16  Detailed characterization of phenotype using advanced imaging (2D echo strain, MRI) and EKG  Discovery of causal or modifier genes in HCM (miRNA genes)  Improved understanding of HCM pathophysiology using transgenic mouse models  Generation of computational models to assess sudden death risk and understand arrhythmias  Design metabolism-based therapies and imaging for preclinical diagnosis/treatment of HCM

17 Aurelio Pinheiro Xiaoping Lin Lea Dimaano Hsin-Yueh Liang Lars Sorensen Fatih Yalcin Nagis Kucukler

18 Cyclic changes muscle length wall thickness Changes are quantifiable Rate of change (strain rate) Extent of change (strain) The Heart is a Mechanical Organ

19 Accepted by 2011 AHA (American heart association) scientific session

20 Miguel Santaularia Stefan Zimmerman Jens-Vogel Claussen David Bluemke

21 Prevalence and Clinical Attributes of T2-weighted edema in HCM  Tissue injury alters T2 relaxation  CMR-based T2 imaging sensitive to regional and global myocardial water content  Myocardial edema an important determinant VariableMild LVHSevere LVH p-value Edema34%80%0.001 DE45%86%0.001 Perfusion Abn 8%33%0.006

22 Paco Bravo Valenzuela Frank Bengel

23 N-13 Ammonia PET/CT STRESS REST STRESS REST Tc-99m Tetrofosmin SPECT 23 F with severe angina and HCM…..sent to psychiatry

24 Roselle Abraham Xiaoping Lin Brian Foster Miguel Aon Sonia Cortasa Brian O’Rourke

25 How does exercise influence phenotype in normal thickness HCM  Examine mitochondrial physiology  Reactive oxygen species Patch clamp 2-photon imaging

26 Rai Winslow Steve Granite Hagit Shatkay Laurent Younes Siamak Ardekani Matt Toerper Mike Shipway Blaid Mbiyangandu (HCM – CVRG liaison) Junaid Afzal Xun Zhou

27 Roselle Abraham Larisa Tereschenko Xiaoping Lin Blaid Mbiyangandu Garry Cutting Steven Steinberg Dan Arking

28 Results: Step1 bioinformatics analysis Potential causative or modifier miRNAs for HCM were identified Fig2. Literature search was performed in two steps: 1) miRNAs regulation dysfunction were observed in human heart (hypertrophy, failing or cardiomyopathy) and In vitro/vivo experiments confirmed their role in cardiac pathological process: hypertrophy, fibrosis and apoptosis 2)Confirm their role in other phenotype secondary to HCM, like metabolic deficiency and electrophysiological dysfunction

29 Results: step 2 Sequencing results Subjects: HCM Patients familial 88 sporadic (?) Hispanic:1; African American: 11; Asian: 1; Caucasian: 176; Others:10 miRNAs studied miRNAs (positive)Findings miR1-1miR-1-1SNP miR1-2miR-1-2SNP miR133a-1 miR133a-2MIR133a-2SNP miR30C-1 miR30C-2 miR29a miR29b-1MIR29b-1SNP, deletion (4 bp) miR29b-2MIR29b-2deletion (1 bp) miR29cMIR29cSNP miR23a miR21MIR21insertion ( 1 bp) miR208a miR208b miR195 miR590MIR590SNP miR15a miR16-1MIR16-1SNP Results overview

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31 Thank you


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