|Ning-Hsuan Tseng, 1st Year
Program: Molecular and Cellular Biology
Advisor: Shelly Peyton
Education: B.S., Biochemical Science Technology, National Taiwan University, 2013
Drug-mediated evolutionary genomics in breast cancer
Breast cancer is one of the leading causes of cancer-related death in women. Despite the developments of chemotherapy, the pre-existing intratumoral heterogeneity and evolutionary genetic alterations in cancer cells strongly affect the patient response to drugs. In addition, previous studies have implicated that the extracellular matrix (ECM) plays a crucial role in modulating tumor growth and metastasis due to the stiffness of microenvironment which may change the mechanism by which cells respond to drugs. To mimic the complex 3D microenvironment, an engineered polyethylene glycol (PEG)- based hydrogel system developed in the Peyton lab will be used to study how cell-material interactions control cell response to drugs and disease progression. In order to identify sensitivities of certain genes to different chemotherapeutic drugs, the use of bacterial CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated 9) genome editing technology suggests an alternative way to rapidly introduce mutations for genetic screening in mammalian cells comparing to conventional methods. By combining the interface of biology and materials will lead to a better understanding of how resistant clones develop during drug therapy and a better therapeutic treatment to patients.
My research focuses on using 3D hydrogel microenvironments to study how cell-materials interactions control biological processes. While several breast cancer cell lines are treated with chemotherapeutic drugs, the genomic profiles shifts which can recreate the processes of how cells are treated in patients. The CRISPR-Cas9 technique will be applied to genetically edit random genes to create a human genome-wide CRISPR library. RNAseq approach will be conducted to quantify genomic evolution of the cancer cell populations. By comparing the results to the pre-treated cell lines, we will be able to characterize acquired-drug sensitive and resistant genes. Overall, in vitro, high-throughput biomaterial platforms will be applied to demonstrate how cancer cells alter in the presence of both drugs and 3D microenvironments.