On Leveraging Immortality, Splicing, and Erythroid Stem Cells

Annie Xia, COL ’25, Cincinnati, Ohio

This summer, I was glad to have the opportunity to continue my work at the Jurado Lab at Perelman’s Department of Microbiology. Coming into Penn as an aspiring physician-scientist, I’d always hoped to hone my research skills and eventually work at the interface of academia and medicine. After the whirlwind that was first semester, I decided to take the leap forward and begin my journey towards this vision. Sure enough, as of January of my freshman year, I began familiarizing myself with the ins and outs of working in a lab — learning procedures, working with cutting-edge technology, and familiarizing myself with the complex mechanisms behind my project. This was taken a step further with deeper immersion through the summer.

The Jurado Lab, rooted in exploring the intricacies of virology and immune systems, aims to understand biologically-honed immune regulatory networks across host and pathogen. A diversity of projects, ranging from exploring Zika virus’s role in fetal resorption within mouse models, to studying unprecedented impacts of nucleated red blood cells in fetal tolerance, drew me to the lab. In particular, the focus of my work centered on the latter: during the semester and especially this summer, I was able to dive into ascertaining the potential role of nRBCs in mediating complex immune responses at the maternal-fetal interface. As someone hoping to one day develop novel therapeutics to treat disease, I was fascinated by the implications of such a project — something previously dismissed as being immunologically insignificant by the scientific community, such as red blood cells, could potentially serve as the backbone of how all successful fetal development! Being a stem cell junkie myself, I was glad to find that one of my goals would be to generate a novel immortalized red blood cell line that modeled the specimens we were examining.

This work, of course, developed through training — first familiarizing myself with the advanced immunological mechanisms behind the project’s overarching theory, then generating a knockout plasmid through CRISPR-Cas9 for the HUDEP (human umbilical cord blood-derived erythroid progenitor) cell line. I read endless journals and scientific papers surrounding the topic and my target cytokine of interest, Growth Differentiation Factor 15 (GDF-15), alongside manuals on experiment techniques. Upon hours of practice and training, I eventually came away with newfound confidence in performing lab techniques like tissue culture, nucleic acid extraction, qPCR, western blot, flow cytometry, and lentiviral transduction. Along with these, I was also able to gain diverse experiences, such as genotyping knockout mouse models for other circulating projects.

Since the immortalized cell model we worked with was known to be karyotypically unstable (often were at risk of losing chromosomes spontaneously), cell and tissue death in the process of manipulating them was no stranger to us. Through my work this summer, I was able to get a taste of what it really means to be in research: to understand and accept failures as they arise, for they are inevitable step of the process. With each setback and unprecedented finding, comes the potential for refining and future betterment. I learned to no longer fear when things happened to not work out, and to nurture patience through the process. This no doubt applies to any task, and as researchers, it is crucial when persevering till the end of a project.

Additionally, leading discussion and actively engaging in journal club each week — spearheaded by our lab in collaboration with others in the department — helped me to more efficiently analyze and pinpoint critical findings in scientific literature. Oftentimes, these journals may seem daunting to dissect and interpret. However, with enough practice and the motivation to learn the higher biology behind each study, the process becomes progressively more natural.

Having finished my summer at the lab, I’m now gearing up for the new academic year as I soon return to campus. I’m glad to have been able to immerse myself in what I love this summer with this funding opportunity, and I anticipate what discoveries the future has to bring!

This is part of a series of posts by recipients of the 2022 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here.

By Career Services
Career Services