Turning Cancer Discoveries into Effective Treatments with the Aid of Mathematical Modeling
Given the multi-scaled pathophysiology involved in tumor initiation and progression, it is becoming more and more important for cancer research to make use of a cross-disciplinary, systems science approaches, in which innovative computational cancer models play a central role. My group is interested in deriving and validating multiscale mathematical models of tumorigenesis and targeted molecular therapeutics.
Cancer Stem Cell driven Tumor Growth, Invasion, and Targeted Therapeutics
A small population of cancer stem cells that share many of the biological characteristics of normal adult stem cells is believed to initiate and sustain tumor growth for a wide variety of malignancies. Growth and survival of these cancer stem cells are highly influenced by tumor micro-environmental factors and molecular signaling initiated by cytokines and growth factors. This work focuses on quantifying the influence of key cytokines on cancer stem cell self-renewal, survival, and invasiveness. With my collaborators at the University of Chicago, we are developing multiscale mathematical models that operate at the following levels: i) the molecular level – capturing cell surface dynamics of receptor-ligand binding and receptor activation that lead to intracellular signal transduction cascades; and ii) the cellular level – describing tumor growth, cellular composition, and response to targeted molecular therapeutics.
Molecular Pathways Associated with Intratumoral Angiogenesis and New Targets for Anti-angiogenic Therapy
Tumor growth and progression is critically dependent on the establishment of a vascular support system. This is often accomplished via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. VEGF ligands are overexpressed in a wide variety of solid tumors, and therefore have inspired optimism that inhibition of the different axes of the VEGF pathway, alone or in combination, would represent powerful anti-angiogenic therapies for most cancer types. When considering treatments that target VEGF and its receptors it difficult to tease out the differential anti-angiogenic and anti-tumor effects of all combinations experimentally because tumor cells and vascular endothelial cells are engaged in a dynamic crosstalk that impacts key aspects of tumorigenesis, independently of angiogenesis. My collaborator and I are developing mathematical models that connect intracellular signaling responsible for both endothelial and tumor cell proliferation and death to population level cancer growth and angiogenesis. We use these models to investigate the effect of bidirectional communication between endothelial cells and tumor cells on treatments targeting VEGF and its receptors in vitro and in vivo.