- To understand the role of the microenvironment in cancer progression and metastasis, with a particular emphasis on vascular tumors and soft tissue sarcomas.
- To determine the molecular regulation of the development and progression of vascular anomalies.
We want to delineate the mechanisms of growth factor signaling pathways in the regulation of pathological angiogenesis in tumors and vascular anomalies (primarily infantile hemangiomas). We are investigating the molecular basis of vascular growth at the molecular, cellular and organism levels with relevant translational applications to the understanding and potential treatment of pathological angiogenesis in cancer and developmental vascular lesions.
Current research avenues
- Investigate the role of Akt and its downstream effectors in the regulation of pathological angiogenesis, and uncover potential novel therapeutic targets in these important growth regulatory pathways.
- Determine how survival signal transduction pathways drive cancer progression through epigenetic changes in the chromatin structure and the expression of growth-regulatory genes in the tumor vasculature.
- Delineate the complex molecular wiring of signaling pathways that control metabolic homeostasis in tumor cells and tumor vasculature.
Akt is activated in tumor blood vessels. Blood vessels (red); activated Akt (green, see arrows)
To elucidate these processes, we use a multi-tiered approach involving molecular biology, cell biology, genomics, metabolomics and bioinformatics. We are developing 3-dimentional in vitro models of tumor, endothelial and stromal cells to study molecular signaling processes, and to test potential therapeutic inhibitors of signaling pathways. Our work utilizes stable tumor cell lines, mouse and human tumor tissues, and primary cell lines derived from these tumors. We also develop mouse models of inducible and tissue-specific overexpression or deletion of a target gene.
Primary mouse endothelial cells stained with acetylated LDL (yellow) resemble a "van Gogh" painting