(3bn) Application of Systems Biology Tools to Investigate Anti-Angiogenic Cancer Therapies

Angiogenesis is the formation of new blood vessels from pre-existing vasculature. This tightly regulated biological process is involved in physiological function such as wound healing and exercise, as well as in pathological conditions, including preeclampsia, ischemic heart disease, and cancer. Inducing angiogenesis is a hallmark of cancer, as tumors cannot grow beyond 1 mm in diameter without eliciting the formation of blood capillaries to supply oxygen and other nutrients. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and its role in cancer biology has been widely studied. Given the action of VEGF in promoting angiogenesis, it has been targeted in various cancer treatments.

Systems biology approaches, including computational models, are useful in gaining insight into the complexity of tumor angiogenesis. These models provide a framework to test biological hypotheses and optimize effective therapies that aim to inhibit tumor vascularization and growth. In this poster, I describe the development of whole-body compartment models of VEGF kinetics and transport in mice and humans and the application of these models to predict the effect of various anti-angiogenic therapies that target VEGF. The mouse model has been optimized using experimental data and complements pre-clinical drug studies. The human model is applied to interpret clinical data. In both instances, the models predict how properties of the tumor microenvironment influence the response to anti-angiogenic agents, which is difficult to quantify clinically. The models aid in the development and optimization of personalized cancer treatment strategies that target the VEGF pathway.

During my doctoral research at Northwestern University, I worked with Profs. Linda Broadbelt and Vassily Hatzimanikatis to apply computational tools to predict and characterize novel metabolic pathways. My current postdoctoral work with Prof. Aleksander Popel at Johns Hopkins University applies a molecular-detailed model of VEGF kinetics and transport to understand the effect of therapeutic agents that inhibit VEGF signaling. In the next phase of my career, I would like to establish a research lab that applies engineering and systems biology tools to study relevant biological questions related to the development of optimal cancer therapies. This work will build upon my training in Chemical Engineering and biomedical research. As a starting point, I aim to develop integrative computational models of cancer metabolism and VEGF-mediated angiogenesis, two processes that characterize cancer. These models will be applied to investigate how tumor cell metabolism and VEGF activation lead to tumor angiogenesis and how these processes can be targeted in order to inhibit the development of cancer. The poster will present the aims of this proposed research.