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Cardiovascular Research Group
Projects
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Genetics
of human cardiovascular disease
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Porf.dr. Rune Frants
Susceptibility genes and metabolic stress.
Aim:
Delineate the genetics of the metabolic syndrome in human and mouse
models.
Tools:
Patient populations, the diet-sensitive APOE3Leiden mouse model,
transcriptomics, metabolomics, and proteomics in a Systems Biology
approach.
Personnel:
Vacanies (Postdoc, AIO, technician)
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Generation
and analysis of mouse models
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NHS
98.144 to Dr. Erik Biessen and Dr. Ko Willems van Dijk
A novel ribozyme based gene therapy for long term
reduction of pro-atherogenic lipoproteins.
Aim:
Development of ribozymes that target genes involved in the production of
VLDL (apoB100 and MTP) aimed at down-regulating VLDL production and
thus reduce hyperlipidemia.
Tools:
Adenovirus mediated gene transfer of ribozymes to the livers of
hyperlipidemic mouse models.
Personnel:
Carlos Vrins (PhD student), Peter van Santbrink (Technician)
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NHS
98.190 to Dr. Ko Willems van Dijk
Estrogen receptor alpha mediated gene regulation in
the liver and its impact on plasma lipid levels and atherosclerosis.
Aim:
Delineate the role of estrogens in the modification of gene transcription
and subsequent effects on the metabolism of lipoproteins in the liver.
Tools:
Adenovirus mediated gene transfer of ligand-independent constitutive
active or dominant negative forms of the estrogen receptor alpha to the
liver of hyperlipidemic mous models.
Personnel:
Christine d'Oliveira (Post-doc), Andre van der Zee (Technician)
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NHS
99.149 to Dr. Ko Willems van Dijk and Dr. Erik Biessen
Adenoviral gene delivery to atherosclerotic
endothelium to restore endothelial function.
Aim:
Develop modified adenovirus vectors that preferentially infect vascular
endothelial cells. Using these re-targeted adenovirus vectors, genes will
be analyzed for their potential to modulate activated endothelial cells
that line (pre)atherosclerotic plaques.
Tools:
Ligands specific for endothelial receptors will be engineered onto the
adenovirus vector, either as part of the adenovirus itself or via
non-covalent coupling.
Personnel:
Emile Gras (PhD student)
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NWO 902.26.220 to Dr. Ko Willems van Dijk
The
role of estrogen receptor a mediated gene regulation in
the vascular
Aim:
Using modified adenovirus vectors that preferentially infect vascular
endothelial cells, the role of estrogen mediated gene regulation will be
investigated in the vascular endothelium.
Tools:
Adenovirus mediated gene transfer of ligand-independent constitutive
active or dominant negative forms of the estrogen receptor alpha to the
vascular endothelium of hyperlipidemic mous models.
Personnel:
Yvonne Krom (PhD student)
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NHS
2000.099 to Prof. Louis Havekes and Dr. Ko Willems van Dijk
In vivo structure-function analysis of apoE to delineate
the functional domains that modulate the metabolism of VLDL.
Aim:
Dissect the role of specific domains of apoE in the various processes that are
affected by apoE.
Tools:
Adenovirus mediated gene transfer of mutated forms of apoE to Apoe-deficient
mice.
Personnel:
Gery Gerritsen (PhD student)
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NHS
2001.141 to Dr. Ko Willems van Dijk
Molecular
mechanims and pathways underlying the effects of estrogens
on lipid metabolism.
Aim:
Delineate the role of estrogens in the modification of gene transcription
and subsequent effects on the metabolism of lipoproteins in the liver.
Follow-up of project NHS 98.190
Tools:
Adenovirus mediated gene transfer of ligand-independent constitutive
active or dominant negative forms of the estrogen receptor alpha to the
liver of hyperlipidemic mous models.
Personnel:
Vacancy (post-doc)
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Dr. Ko Willems van Dijk
Peripheral tissues and metabolic stress
Aim:
Delineate the mechanism of high fat feeding on the development of the
metabolic syndrome.
Tools:
The diet-sensitive APOE3Leiden mouse model, transcriptomics, metabolomics,
and proteomics in a Systems Biology approach.
Personnel:
Vacancy (AIO)
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