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SUMMARY:Systems biology of angiogenesis in ischemic diseases - Popel\, A (
 Johns Hopkins)
DTSTART:20090721T081500Z
DTEND:20090721T090000Z
UID:TALK19136@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:Angiogenesis is the formation of new blood vessels from pre-ex
 isting microvasculature. Angiogenesis is important under physiological and
  pathological conditions (e.g.\, exercise\, ischemic heart and peripheral 
 vascular diseases). Over 70 diseases have been identified as angiogenesis 
 dependent. Angiogenesis involves numerous processes such as: cell sensing 
 of oxygen levels during hypoxia\; upregulation of vascular endothelial gro
 wth factor (VEGF) by parenchymal and stromal cells\, and of matrix metallo
 proteinases (MMPs) by endothelial cells\; extracellular matrix (ECM) prote
 olysis and release of matrix-bound growth factors\; endothelial cell migra
 tion\, proliferation and differentiation\; tubulogenesis or formation of c
 apillary tubes\; network morphogenesis\; and vessel maturation and remodel
 ing. We use computational approaches to explore the mechanisms and quantit
 ative features of these processes. We use post-genomic bioinformatic appro
 aches as an aid to model development. We have developed a series of molecu
 lar-level computational models that serve as modules in multiscale integra
 tive models. These include a model of Hypoxia-Inducible Factor HIF1 regula
 tion\; models of interactions of several VEGF isoforms with their receptor
 s VEGFR1\, VEGFR2\, co-receptor Neuropilin-1 and heparan sulfate proteogly
 cans\; and a model of ECM proteolysis by MMPs\, specifically MMP2\, MMP9 a
 nd membrane-type MT1-MMP\, in the presence of tissue inhibitors of metallo
 proteinases (TIMPs). In addition to these biochemically and biophysically 
 detailed molecular-level models\, we have developed a compartmental pharma
 cokinetic model that allows us to predict distribution of VEGF isoforms an
 d intermediate products upon administration of pro-angiogenic factors\, e.
 g. via gene delivery. The models will lead to a better understanding of th
 erapeutic interventions in disease conditions including pro-angiogenic app
 roaches to ischemic heart disease and peripheral vascular disease. 
LOCATION:Seminar Room 1\, Newton Institute
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