Mayumi Oakland successfully defends PhD thesis
Wednesday, January 09, 2013
Mayumi Oakland successfully defended her PhD thesis, "Improving Lentiviral Vector-Mediated Gene Transfer by Understanding Cellular Barriers," on Wednesday, January 9, 2013. Oakland is pictured here with her mentor, Dr. Paul B. McCray, Jr.
CF is a genetic disorder of which lung disease is the leading cause of morbidity and mortality. One attractive strategy for the treatment of CF lung disease is to directly deliver CF transmembrane conductance regulator genes to airway epithelia. Although promising results have been reported, barriers present in the lung make successful gene transfer to the respiratory tract difficult. In order to improve gene transfer strategies in the intrapulmonary airways, we need to identify the bottlenecks of transduction for the vector system. A previous study reported that feline immunodeficiency virus (FIV)-mediated gene transfer was more efficient in the nasal airways in mice than the intrapulmonary airways. We demonstrate that host immune response is not the major barrier preventing efficient FIV-mediated transduction in the intrapulmonary airways. Instead, our results suggest that differentially expressed cellular factor(s) specific for GP64 or FIV vector may be the major barrier(s) for FIV vector-mediated gene transfer in the murine intrapulmonary airways.
In addition, we characterized a mucin domain-deleted Ebola virus (EBOVΔO) glycoprotein mutant with increased transduction for their potential gene transfer application in the airways. The EBOVΔO 5-mer mutant was generated based on mutants with an increased transduction as identified by alanine scanning mutagenesis. We show that VSV pseudotyped with the 5-mer mutant increased transduction both in vitro and in mice when compared to the wild-type. Structural analysis demonstrated that 5 mutations were located proximal to the GP1-GP2 interface. Enhanced transduction likely results from a lower energy metastable state rather than changes in host cell receptor utilization. FIV pseudotyped with 5-mer also shows increased transduction in multiple cell lines. Identification of barriers in intrapulmonary airways and improvements of vector systems will help the advancement of gene therapy for CF.
Mayumi was born in Tochigi, Japan. She grew up with her younger sister, Sayaka, and was brought up by her loving parents, Morio and Ruriko. After graduating from Utsunomiya Girl’s High School, she moved to Pueblo, Colorado to attend the University of Southern Colorado, majoring in Biology. She later transferred to Colorado State University and became very interested in microbiology. She received her B.S. in microbiology in 2003. After working as a translator in Japan for half a year, she moved to Ames, Iowa to obtain her M.S. in Genetics at Iowa State University. There she worked on characterizing a lipoprotein-encoding operon in Campylobacter jejuni under the guidance of Dr. Qijing Zhang.
Mayumi entered the Microbiology Ph.D. program at the University of Iowa in August 2007. She joined Dr. Paul McCray’s laboratory in Spring 2008 and started on projects involving lentiviral vector-mediated gene transfer to airway epithelial cells. Mayumi is thankful to Dr. McCray for his guidance and support, Dr. Patrick Sinn for his great mentorship, and all the past and present McCray members for their help and friendship. She has published a first-author review on advancement in gene transfer strategies for cystic fibrosis (CF) lung disease. She also has a first-author paper on investigating potential barriers to lentiviral vector-mediated gene transfer in the airways of mice, which is in press. She has had opportunities to present her work at several conferences including the American Society of Gene & Cell Therapy meetings in Seattle and Philadelphia.
Before Mayumi stepped foot in Iowa, she only knew it from the musical State Fair, and she was very pleased to find Iowa to be such a friendly and beautiful place to live. She enjoys collecting cookbooks and loves the fact that most of the results come out as expected and delicious! She also enjoys going on hikes with her husband, Dan, and their miniature Aussie, Magni. When she arrived in the States, she only had two blue suitcases and couldn’t speak much English. She is sincerely grateful that her American life is now filled with friends, families, great memories, and love.