The major focus of this laboratory is to understand
the molecular mechanisms of hypertrophy and heart
failure. To achieve this goal, my laboratory uses
a strategy that combines state of the art molecular
techniques to generate transgenic and gene targeted
mouse models, combined with sophisticated physiologic
measures of in vivo cardiac function.In this manner,
candidate molecules are either selectively overexpressed
in the mouse heart or ablated by homologous recombination,
which is followed by an in-depth analysis of the physiological
phenotype. To model human cardiac disease, we have
created several models of cardiac overload in the
mouse using both microsurgical techniques and genetic
models of cardiac dysfunction.
Areas of research:
- Signaling: G protein-coupled receptor signaling
in hypertrophy and heart failure focusing on the
interaction of phosphoinositide-3 kinase with ß-adrenergic
receptors.
- Identification of Strain Specific Modifiers: Genome
mapping of microsatellite markers by SSLP to identify
gene modifiers of the heart failure phenotype using
mouse models of disease.
- Molecular Physiology: In depth physiological analysis
of cardiac function in genetically altered mice
to understand the role of G protein-coupled receptor
signaling pathways on the development of heart failure
in vivo.
- N-ethyl-N-nitrosourea (ENU) Mutagenesis Program:
To detect mutations in genes previously unrecognized
to affect cardiac hypertrophy and heart failure.
Chemical mutagenesis is used to create new mouse
strains that can be bred into disease-sensitized
mouse models to map disease susceptibility genes.
