During my postdoctoral training, I have developed a CRISPR/Cas9-based system to genetically modified hematopoietic cells for understanding hematopoiesis, modeling hematopoietic disorders, and developing gene therapy for monogenic disorders. As an independent PI of Wells Center, Department of Pediatrics, my group will focus on both clinical-oriented research (Modeling and developing gene therapy for hematopoietic disorders) and basic research (Exploring novel in vivo functions of genes in hematopoiesis and lymphomagenesis).
For a cancer-related project, I will explore the function of the Oligosaccharyltransferase (OST) complex in multiple myeloma development. N-glycosylation is one of the most prevailing post-translational modifications of secretory and membrane-bound proteins. This modification is crucial for protein folding and trafficking, endoplasmic reticulum homeostasis, extracellular recognition, and signaling. The transfer of N-glycan to the asparagine residues of the nascent protein at the glycosylation sequon Asp-X-Ser/Ther is catalyzed by the oligosaccharyltransferase (OST), a multi-subunit complex. In humans, there are two distinct OST complexes: OST-A and OST-B that act co-translationally and post-translationally, respectively. However, they share 6 core subunits (RPN1, RPN2, OST4, DAD1, TMEM258, and DDOST). The aberrance of N-glycosylation has been associated with many solid tumors and congenital disorders. However, the functions of OST complexes in hematopoiesis and lymphomagenesis are virtually unknown.
By exploiting the publicly available data from Oncomine and Cancer Cell Line Encyclopedia, I found that all shared subunits of OST complexes express as abundantly as cMYC and POMP in multiple myeloma (MM) cell lines and patient-derived cells. My pilot experiments showed that CRISPR/Cas9-mediated knocking out these subunits negatively affected the survival of human MM cell lines. This indicates the potential roles of the OST complexes in human MM development. Additionally, inhibition of the OST complex suppresses the growth of MM cell lines via cell cycle arrest and ER induction. Of note, OST complex inhibitor and bortezomib show synergistic effects in terms of killing MM cell lines. Next, we will exploit the xenograft model to investigate functions of OST complex in MM development in vivo using both MM cell lines and patient-derived cells.
Post-doctoral Fellowship - University of Alabama, Birmingham, AL 04/2016
Post-doctoral Fellowship - KAIST University, Daejeon, South Korea 04/2012
Post-doctoral Fellowship - Max Delburck Center for Molecular Medicine, Berlin, Germany 02/2020
Ph.D. - KAIST University, Daejeon, South Korea 02/2012