Lab
Hoeppner Lab
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Statement of Research Interest
Development of zebrafish models of vascular permeability and cancer metastasis
VEGF induces vascular permeability in stroke, heart attack, and cancer leading to many pathophysiological consequences. Following cerebral or myocardial infarction, VEGF induces gaps between adjacent endothelial cells in ischemic tissue and the resulting vessel leakiness causes deleterious edema formation and tissue damage. In cancer, VEGF-mediated permeability promotes tumor angiogenesis and metastasis. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of permeability do not exist. We developed a heat-inducible VEGF transgenic zebrafish model through which vascular permeability can be monitored in real-time. Using this approach with gene silencing techniques, as well as knockout mice, we described a novel role of phospholipase Cβ3 (PLCβ3) as a negative regulator of VEGF-mediated vascular permeability by tightly regulating intracellular calcium release. We have also used this zebrafish model to elucidate the role of RhoC and other molecules in vascular homeostasis. The zebrafish vascular permeability model represents a straightforward method for identifying genetic regulators of VEGF-mediated vascular as promising targets for cancer, heart disease and stroke therapies. We also developed a zebrafish xenograft model of human cancer cell metastasis, which was used in two separate studies to support our findings from murine cancer models. Although beyond the scope of our zebrafish work, my research group studies the role of dopamine and VEGF signaling in lung cancer progression and drug resistance.
VEGF induces vascular permeability in stroke, heart attack, and cancer leading to many pathophysiological consequences. Following cerebral or myocardial infarction, VEGF induces gaps between adjacent endothelial cells in ischemic tissue and the resulting vessel leakiness causes deleterious edema formation and tissue damage. In cancer, VEGF-mediated permeability promotes tumor angiogenesis and metastasis. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of permeability do not exist. We developed a heat-inducible VEGF transgenic zebrafish model through which vascular permeability can be monitored in real-time. Using this approach with gene silencing techniques, as well as knockout mice, we described a novel role of phospholipase Cβ3 (PLCβ3) as a negative regulator of VEGF-mediated vascular permeability by tightly regulating intracellular calcium release. We have also used this zebrafish model to elucidate the role of RhoC and other molecules in vascular homeostasis. The zebrafish vascular permeability model represents a straightforward method for identifying genetic regulators of VEGF-mediated vascular as promising targets for cancer, heart disease and stroke therapies. We also developed a zebrafish xenograft model of human cancer cell metastasis, which was used in two separate studies to support our findings from murine cancer models. Although beyond the scope of our zebrafish work, my research group studies the role of dopamine and VEGF signaling in lung cancer progression and drug resistance.
Lab Members
| Alam, Sk. Kayum Post-Doc | Astone, Matteo Post-Doc |