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SUMMARY:Ventricular Remodeling: Population Variation in Congenital Heart D
isease and Data Uncertainty in Systems Mechanobiology - Andrew McCulloch (
University of California\, San Diego)
DTSTART:20190605T090000Z
DTEND:20190605T100000Z
UID:TALK125548@talks.cam.ac.uk
CONTACT:INI IT
DESCRIPTION:Congenital heart defects are the commonest class of birth defe
ct and are associated with a wide range of anatomic lesions which are freq
uently life-threatening without surgery early in life. The success of thes
e interventions means that there are now more adults than children with co
ngenital heart disease (CHD)\, but many of these patients are at risk of a
dverse ventricular remodeling and heart failure. Managing these patients a
nd predicting when to intervene are important clinical decisions and cardi
ac MRI exams every few years are common. However how to use the structural
and functional data from these studies is complicated by the atypical and
widely varying ventricular shapes in many CHD such as repaired Tetrology
of Fallot. Here\, I describe how ventricular shape atlases derived from pr
incipal component analysis of parametric shape models can be used to under
stand patient variation and identify potential markers of adverse ventricu
lar remodeling in CHD.
Underlying ventricular modeling processes
are myocyte signaling pathways\, many of which are mechanosensitive. Genom
e scale data such as RNA-seq provide a way to experimentally validate the
predictions of cell signaling models. In a model of myocyte mechanosignali
ng\, we were able to correctly predict the responses over over 70% of appr
oximately 800 genes to longitudinal and transverse stretch. However\, unc
ertainty in underpowered transcriptomic data sets is a significant impedim
ent to more stringent model validation and optimization.
Supporte
d by NIH grants
LOCATION:Seminar Room 1\, Newton Institute
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