Andrew C. Dudley

Solid tumors resemble dysfunctional organs complete with their own vascular network that supplies blood, oxygen and nutrients. Tumor vessels also form conduits for the dissemination of tumor cells throughout the body. Thus, some cancers may be reversible or left in a dormant state by specific elimination of the blood vessels feeding them. Generally, three ingredients are needed to make a tumor blood vessel: endothelial cells form lumens, mesenchymal cells form perivascular cells and hematopoietic cells guide and unite nascent vessel sprouts. Some of these vascularforming cells are conscripted by tumors from nearby tissue and some are from bone marrow. Our lab seeks to understand how tumors make new blood vessels in order to better design and implement the anti-angiogenic therapies that can destroy them.

We currently have three projects in the lab:

1) To determine the role of bone marrow-derived cells during tumor growth and angiogenesis.

Most tumors hijack a heterogeneous population of stromal cells from nearby tissue and from the circulation. Some of these stromal cells are vascular progenitors used as building blocks for tumor blood vessels. We are using transgenic mice to genetically mark mesodermal stem cells (MPC) in the bone marrow. This model will help us determine the kinetics of MPC mobilization, fate and differentiation once recruited to growing tumors.

2) Developing in vivo models of tumor vascular networks.

Tumor vessels are poorly formed, leaky and dysfunctional. These abnormalities can contribute to tumor progression. For example, leaky vessels may facilitate metastasis while activated tumor endothelium may enable the recruitment of leukocytes that create a permissive environment for tumor growth. We are using isolated cultures of tumor endothelial cells to re-create tumor vascular networks in mice. Our goal is to identify endothelial cell-derived paracrine factors that control leukocyte tropism and differentiation in tumors.

3) Understanding resistance to anti-angiogenic therapies.

Anti-angiogenic therapies have not produced a sustained benefit in cancer patients. Most patients on anti-angiogenic drugs experience brief tumor stasis followed by tumor rebound. An unexpected finding is that some tumor cells may acquire properties of vascular cells (often termed vasculogenic mimicry). We are using mouse models to identify tumor cells with properties of vascular cells and determine their role in mediating resistance to anti-angiogenic therapies.

2000- Prevent Blindness America Fellowship

2003- The Juvenile Diabetes Foundation Travel Award

2005- National Institute of Health LRP

2009- Howard Temin Pathways to Independence Award, National Cancer Institute (NIH)

2011-University Cancer Research Fund Innovation Award

2013-Junior Faculty Development Award UNC Chapel Hill