To date, most in vitro pancreatic cancer studies have been conducted on two dimensional (2D) tissue-culture plastic dishes (TCP) that are unnaturally stiff (E > 1 GPa). The ultrahigh stiffness of a 2D surface not only un-naturally polarizes the attached cells, but also causes the cells to behave differently due to abnormal mechano-sensing. 2D cell culture techniques are also inadequate in the study of tumor cells, which are highly influenced by the stromal tissues (i.e., desmoplasia, dense extracellular matrices deposited by activated pancreatic stellate cells) found in three-dimensional (3D) tumors. It is also believed that desmoplasia communicates with pancreatic cancer cells to promote tumor progression and to hinder drug penetration and efficacy. Although a few studies have explored the utility of 3D matrices, such as Matrigel, for pancreatic cancer research, the commercially available matrices are mechanically weak and contain ill-defined and un-controllable biochemical components that may confound the experimental results.
Our central hypothesis in this research project is that a synthetic tumor niche with dynamically and modularly adaptable properties can be used to elucidate the influence of extracellular matrix (ECM) cues on the growth, morphogenesis, and drug efficacy in PDAC cells. Toward this end, we are interested in developing synthetic hydrogels that can be reversibly stiffened or softened in a range relevant to pancreatic cancer cells. Specifically, we are developing innovative dynamic desmoplasia-mimetic hydrogel matrix to encapsulate pancreatic cancer cells (e.g., PANC-1, COLO-357, and ASPC1) and study their growth, morphogenesis, and epithelial-mesenchymal transition (EMT). We are also developing strategies to independently and reversibly modulate the biophysical and biochemical properties of cell-laden hydrogels in order to delineate the influence of various immobilized and soluble extracellular factors on pancreactic cancer cell fate processes, including drug resistance. The information obtained from this study will open new therapeutic options for treating the lethal pancreatic cancer.
Post-doctoral Fellowship - University of Colorado, Boulder, CO 2010
Ph.D. - Clemson University, Clemson, South Carolina 2007
M.S. - National Taiwan University, Taiwan 1998
