The primary research interest of the Murfee Laboratory is to better understand the cellular dynamics involved in adult microvascular remodeling. Specifically, we apply in vivo, in vitro, and computational bioengineering approaches to investigate the regulation of vascular patterning and the functional relationships between microvascular remodeling and other processes such as neurogenesis, lymphangiogenesis and inflammation. In general, our work will provide valuable insight for the engineering of functional vascularized tissues and for understanding vascular dysfunction associated with multiple pathological conditions, such as hypertension, tumor growth, and wound healing.

1. Perivascular Cell Lineage during Microvascular Remodeling

Vascular remodeling is a complex continuum that incorporates the formation of new capillaries from pre-existing vessels, termed angiogenesis, capillary acquisition of a perivascular cell coating, referred to as arteriogenesis, and the acquisition of an arterial/venous (A/V) phenotype. Perivascular cells, including both smooth muscle cells (SMCs) and pericytes, are involved in each of these processes. To fully understand how microvascular networks grow and respond to altered environmental conditions, we must understand the mechanistic importance of perivascular cell phenotypic differences along the hierarchy of microvascular networks and from which cell populations do perivascular cells originate.

2. Identifying Blood Vessel-Lymphatic Interactions during Lymphangiogenesis

Lymphatic dysfunction is linked to multiple pathological conditions, including lymphedema and cancer metastasis, yet the mechanisms of lymphatic growth remain largely unknown especially in comparison to what is known regarding vascular remodeling. The aim of this work is to identify the functional interrelationships between lymphatic and blood vessel network growth. Specifically our objectives are to 1) to evaluate the spatial and temporal patterning dynamics of network growth during lymphangiogenesis in relation to angiogenesis, and 2) to better understand how lymphatic endothelial cell structure influences interstitial fluid uptake.

3. Microvascular Patterning Alterations Associated with Hypertension

Genetic hypertension is associated with an increase in vascular resistance due, in part, to microvascular rarefaction characterized by fewer arterioles, capillaries, and/or venules. Given that the development of elevated blood pressure is thought to be pre-ceded by this phenomenon, therapies aimed at reversing microvascular rarefaction are potential candidates for hypertension treatments. However, the influence of microvascular alterations associated with rarefaction on microvascular resistance during development of the disease and the ability of hypertensive networks to undergo angiogenesis remain unclear. In order to gain novel insight into the microcirculation’s role in hypertension and the development of therapies aimed at reversing rarefaction, the aim of this work is to better understand the influence of structural alterations at the microvascular network and cellular levels on microvascular function over the time course of the disease.