Student Profile: Insoon Chang
About my path to academic dentistryI was born in Seoul, Korea and came to the United States in 1995. I attended The University of Texas at Austin and received my B.S. in Biochemistry in 2005. During my undergraduate training, I worked in Dr. Ellen Gottlieb’s Molecular Biology lab, studying muscular dystrophy, for one year, and in Dr. John McDevitt’s Materials Science lab, working on superconductors, for 3 years. After graduation, I worked for 2 years as a research assistant and coordinator in Dr. Xiaomin Chen’s structural biology lab at M.D. Anderson Cancer Center in Houston, TX.
As I became more and more involved with research, I wanted to learn how to implement knowledge into the real world by considering the big picture, making connections between problems in meaningful and significant ways. In conjunction with my long time interest in dentistry and oral cancer research, I applied and received my M.S. degree in Oral Biology from UCLA in 2010. I am currently in my second year of a seven-year DDS/PhD program at the UCLA School of Dentistry. Dr. Cun-yu Wang is my research mentor. I joined his lab in the summer of 2007, shortly after he transferred from the University of Michigan. I am very fortunate to work under Dr. Wang’s mentorship, and to be able to continue working in his lab as I conduct my Ph.D research, as well.
I am supported in my studies and research by a T32 training grant, awarded through the National Institutes of Health. . I am also part of the Academic Track program supported by an R25 grant. The Academic Track program allows me to network with both the UCLA faculty and the alumni in various aspects of the dental field, and offers mentorship in areas of teaching, research, and leadership. Both the T32 and R25 grants have provided me with an opportunity to develop independence and professionalism, as well as the ability to overcome further challenges, aiding me in becoming a successful researcher, clinician, and academician.
About my research
I work on 2 independent research projects.
1. Cancer Stem Cell
The cancer stem cell (CSC) model of tumor development and progression indicates that a small subset of tumor cells is responsible for tumor initiation, growth, and metastasis. These rare cells have a capability to self-renew and to give rise to heterogenous differentiated progeny, maintaining tumor growth indefinitely. In addition, CSCs exhibit drug resistance, inhibiting its complete elimination through chemotherapies. Today, the CSC working model is being progressively extended to several solid tumors, and recent studies demonstrate that the Head and Neck Squamous Carcinoma Cells (HNSCC) also contain a rare subset of cells that are clonogenic in vitro and tumorigenic in vivo. Isolation of CSC from tumor tissues and cancer cell lines is critical for further investigation. One of the well-characterized approaches of CSC isolation is to separate CSC-like side populations (SP) from cancer samples. We have successfully purified SP cells from high metastatic HNSCC. We propose to investigate that SP cells are responsible for HNSCC cancer metastasis and resistance to chemotherapy. Understanding the biological properties of SP cells will facilitate the development of new therapeutic approaches to prevent HNSCC tumor progression and metastasis.
2. Proteasome Inhibitor and Histone Deacetylase Inhibitors
Proteasome inhibitor, PS-341, has been proposed as an alternative approach for conventional chemotherapy for head and neck squamous cell carcinoma (HNSCC), a common and lethal malignancy. However, clinical studies showed that the cytotoxicity of PS-341 remains limited when used as a single agent. Recently, histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents due to its ability to enhance PS-341-induced cytotoxicity for various malignancies. In this study, we examined both in vitro and in vivo interactions between PS-341 and HDAC inhibitor trichostatin A (TSA) in HNSCC. We found that, while TSA treatment alone did not induce apoptosis; it significantly enhanced PS-341-induced apoptosis in HNSCC cells. Mechanistically, TSA increased PS-341-induced Noxa expression and caspase 3 and 9 activation in HNSCC cells. In addition, consistent with findings of various malignancies, our results demonstrated that TSA enhanced PS-341 sensitivity by inhibiting HDAC6 activity. Inhibition of HDAC6 activity by co-treatment of PS-341 and TSA resulted in suppression of two distinct cytoprotective pathways: dephosphorylation of heat shock factor 1 (HSF-1) and abrogation of aggresome formation. Constantly, the knock-down of HDAC6, HSF-1, and Autophage protein 5 (ATG5), respectively, in HNSCC cells significantly enhanced apoptosis induced by PS-341 alone. Moreover, simultaneous injection of PS-341 with TSA efficiently inhibited tumor growth compared to treatment with PS-341 alone in a murine xenograft model established with subcutaneous injection of HNSCC cells. Taken together, our results provide new insight into the mechanisms of synergistic antitumor activity of PS-341 and HDAC inhibitor regimen, offering a new therapeutic strategy for HNSCC patients.