Creating Biomedical Technologies to Improve Health

2018 BESIP Project

Cellular and Molecular Biology Section
NCI
Mentor Name: 
Giovanna Tosato, M.D.
Mentor Email: 

Laboratory and Project Description

The laboratory studies the contribution of blood vessels to the development and progression of cancer. This contribution differs in different contexts. Our laboratory is interested in the contribution of the endothelium to tumor growth in three such contexts. A) Within tumors, the vasculature contributes to accelerate tumor growth by providing nutrients and oxygen to the tumor cells. Drugs that reduce the tumor vascular supply are FDA-approved for the treatment of certain cancers, but their effects are generally modest. We are developing a new approach centered on the function of EphrinB2 signaling that targets the endothelium differently from what has been previously done. Briefly, previous anti-angiogenic drugs prevent new vessel formation, whereas we are targeting the already formed tumor vasculature. B) Within the bone marrow, the vascular endothelium of sinusoidal vessels provides a port of exit for the hematopoietic cells to reach the peripheral circulation, and from this site reach tumors where they contribute to tumor growth by differentiating into pro-tumorigenic myeloid cells. We have identified a novel mechanism centered on EphB4 signaling whereby the exit of pro-tumorigenic hematopoietic cells can be reduced. We are now further studying and developing this system for potential applications in cancer. C)  Within the intestinal stem cell niche, we are studying the contribution of the endothelium to the development of colon cancer. Our focus is on the interactions between a Notch ligand, Jagged-2, and the intestinal stem cells and other cells within the niche, particularly the endothelium. Ongoing results have identified a number of critical new functions of Jagged-2 in the endothelium that may be critical to colon tumor formation.

We use a variety of approaches in our research, including studies in silico, studies in vitro using molecular biology, biochemistry and cell biology techniques, pre-clinical experimentation in mice and use of patient specimens.

SIP students will be exposed to research on these topics and will be engaged in a specific aspect of one of these projects, commensurate with the candidate expertise, desires, time constrains and probability of success in the experimental part. The candidates will acquire expertise in fields such as vector construction, primers design, protein analysis, flow cytometry, immunohistochemistry and fluorescence microscopy, use of confocal microscopy, animal experimentation.