I am interested in working in the areas of therapeutic drug development and delivery, cell and tissue engineering, protein engineering, and synthetic biology. I have expertise in analyzing and engineering therapeutic protein-producing mammalian cells, specifically Chinese hamster ovary (CHO) cells. I also have experience engineering other cell types including bacteria, yeast, and human embryonic kidney (HEK) 293 cells. I am confident I can extend my cell culture experience to other cell types including plant, HeLa, or induced pluripotent stem cells (iPSCs). I have expertise in studying the unfolded protein response (UPR) and am interested in studying other signaling pathways such as PI3K/AKT, JAK-STAT, and the cell cycle. As such, I am interested in roles focused on protein design, antibody engineering, cell line development, biologics expression, and synthetic biology. I look forward to working on projects where I can contribute to a team environment in order to improve and create products which will benefit society.
Research Experience
My research experience focuses on analyzing and engineering proteins, protein secretion, and ER stress across cell types, with a specialization in mammalian cells. As an undergraduate at Auburn University, I worked in Dr. Robert Chambers's lab to measure enzyme activity of a Polymer Conjugated Enzyme (PCE) system designed to assist in metabolizing liver toxins in vivo. Early in my doctoral career at Clemson University in Dr. Mark Blenner's lab, I worked on projects focused on characterizing and engineering various yeast species for growth in ionic liquids and expression of lignin-degrading enzymes. These experiences jumpstarted my interests in genetic and protein engineering and therapeutic drug development and delivery. In my dissertation work, I worked with the labs of both Dr. Blenner and Dr. Sarah Harcum to characterize the events and subsequent signaling mechanisms leading to CHO cells undergoing stress during biomanufacturing. These host cells are the most common protein production platforms due to efficient post-translational modification machinery and endoplasmic reticulum (ER) quality control. However, high titers of recombinant proteins pose a burden and lead to an imbalance in ER homeostasis. Accumulation of improperly folded proteins in the ER initiates the UPR to restore ER homeostasis. Cell stress, as a result, can have a significant impact on productivity, product titer, and product quality, which are all of particular importance in production of therapeutics and pharmaceuticals.
My work has focused on understanding the dynamics of the UPR in CHO cell lines producing distinct protein products, with the aim to manipulate this signaling response for improving recombinant protein production. I have been able to model the transient nature of UPR in different CHO cell lines as well as identify new targets which are hypothesized to enhance protein folding. As outlined in my 2024 research paper, I compared UPR activation in an IgG1 producer compared to its host cell line. Using lentiviral delivered shRNA, I knocked down two targets, ATF6β and WFS1, in the IgG1 producer and generated stable knockdown pools. Stable knockdown of ATF6β decreased cell growth without decreasing titer; however, knockdown of WFS1 decreased titer without affecting growth. Knockdown of ATF6β improved the UPR specifically later in fed-batch leading to increased overall productivity. At the time of this abstract submission, I have a paper in review and have another paper in preparation. In the pursuit of my doctorate, I have gained experience with a wide variety of molecular biology techniques including (but not limited to) quantitative polymerase chain reactions (qPCR), transcriptomic analysis of RNASeq datasets, lentivirus generation, and short hairpin RNA (shRNA) interference. I have also been fortunate to work with many great people with diverse backgrounds in order to achieve common goals.