Microenvironmental conditions (e.g., 3-D cell-cell and cell-extracellular matrix interactions) are critically important in tumor induction and progression, and mediate the establishment of metastases at preferential target sites. By exploring diversified tissue-engineered model systems and polymeric growth factor delivery strategies, our research aims at elucidating microenvironmental events that currently impair the prognosis of cancer patients and to develop new drug delivery systems for more effective treatment of cancer.
Tumor-stroma interactions in cancer pathogenesis
The tumor stroma regulates key characteristics of malignancy including tumor growth, vascularization, and metastasis; however, many of the intrinsic signaling mechanisms are far from being unraveled. In carcinomas, the most common type of cancer in adults, stroma effects are mediated in large part via myofibroblast and adipocyte derived signals. We are studying molecular and cellular events involved in the recruitment of myofibroblasts by immune cells and investigate unidentified functions of adipose tissue potentially involved in the promotion of breast cancer.
Tumor metastasis in engineered bone microenvironments
Metastasizing tumor cells often colonize trabecular regions of skeletal bone and lead to secondary tumor growth with different patterns of bone effects ranging from osteolytic to osteoblastic occurrence. Increasing evidence indicates that pathological bone remodeling involves tumor-derived soluble factors, but it remains unclear whether microarchitectural and biomechanical stimuli may also play a pivotal role in this process. We are investigating the progression of bone metastases as a function of differential structural and biomechanical features of trabecular bone by using diversified engineered matrices and tumor models.
3-D in vitro models of vascularized tumors and tumor angiogenesis
We utilize hydrogel scaffolds for the 3-D culture of tumor cells in oxygen-controlled systems, and for the in vitro study of the chemical and physical factors that influence tumor angiogenesis. Microfluidic channel-embedded alginate scaffolds are used to study the effects of complex spatiotemporal variations in tumor oxygenation on pro-angiogenic factor secretion. Collagen scaffolds are utilized as a remodelable format that enables study of the dynamic interplay, in a fully-controlled system, between different cell types involved in tumor angiogenesis, including tumor, stromal, endothelial and bone marrow derived cells. The ultimate goal of this project is to develop a fully vascularized tumor model in a remodelable and physiologically relevant material as a powerful in vitro tool to enable studies of all aspects of tumor development, from the acquisition of initial vasculature to metastasis. This research is carried out in close collaboration with Professor Abraham Stroock in Chemical and Biomolecular Engineering.
Engineered Microenvironments to Study Brain Cancer Tumorigenesis
Glioblastoma multiforme (GBM) is an extremely aggressive brain cancer characterized by high therapeutic resistance and dismal survival rates. These tumors contain a minute population of self-renewing and undifferentiated cells, termed cancer stem cells (CSCs), which reside in localized brain parenchyma and are believed to play a key role in the ability of GBM to survive conventional therapies. In order to study their behavior in a physiologically-relevant context, we utilize tissue engineering approaches to recreate the three-dimensional microenvironment where CSCs reside in vivo. This allows us to precisely control nutrient availability, cell-cell interactions, and provides a unique opportunity for drug testing on CSC survival. We implant these engineered tumors in mice to validate our benchtop findings, and use state-of-the-art imaging techniques to monitor GBM growth and metastasis in vivo.