Molly (Mary D.) Frame, Ph.D.
Project #1. Funded by The National Institutes of Health since 1996, this project examines physical and genomic mechanisms involved in the control of blood flow within the smallest blood vessels. The emerging picture is that flow is not controlled in individual vessels, but instead as a concerted effort by a specific group of vessels called a network. This involves multiple flow paths, and we examine resistance and flow in series and in parallel using computational fluid dynamics of low Re flow conditions. Of specific interest are the velocity profiles at bifurcation regions. The cellular mechanisms that appear to be most important in the living animal are wall shear stress sensing and vascular communication between adjacent cells through the gap junctions, including connexin 43. One particular type of response stimulated by nitric oxide initiates a reverberating communication along the network, with long lasting effects on subsequent responses. To further understand the role of physical and genomic mechanisms within the vascular network, we examine endothelial cell behavior within tissue engineered vascular networks in a scale model; we make this model at the Cornell Nanofabrication Facility.
Project #2. Funded by the American Heart Association since 2000, this project examines how the connective tissue elements that hold small blood vessels in place also initiate vascular communication signals that regulate where the blood flow goes within a network. The hypothesis is that flow is coordinated at the level of the network to meet the metabolic needs of the tissue. Specifically, we examine the terminal arteriolar network control of flow by the vitronectin receptor. Important components to this response appear to be chloride channel activation, and wall shear stress sensing and communication along the upstream flow path. By using a genomic approach developed in our lab, we alter the protein expression of individual proteins within the hamster cheek pouch tissue. We have determined a vital link between connexin 43 and flow sensing that is essential for the network to behave in concert.
New projects expand the tissue
engineering associated with Projects #1 and #2 with the goal of constructing
vascular networks that are viable for implantation, and eventually could
be used to promote angiogenesis in vivo. Key in development of this
project is use of nanofabricated biodegradable scaffolding made by collaborators,
Drs. Chu and Hsiao, in the Department of Chemistry, SUNY Stony Brook,
and targeted drug delivery vesicles made by collaborator, Dr. Weiliam
Chen, in Biomedical Engineering.