Gabby working in a biosafety hood, culturing mammalian cells

Author: Gabby Bulliard | Major: Biomedical Engineering | Semester: Spring 2024

My name is Gabby Bulliard, and I am a recent graduate from the Biomedical Engineering undergraduate program. This research was performed under Dr. Chris Nelson in the Biomedical Engineering department in the spring semester of 2024. I will be continuing my education in the Biomedical Sciences at the University of Texas Southwestern Medical Center in their Ph.D. program this coming fall.

This project was a section of the dissertation of one of my lab’s Ph.D. students, Harumi. Her dissertation focused on expressing proteins in skeletal muscle through genetic therapy, which is a growing avenue for treating genetic diseases and cancers. My part of the project focused on optimizing non-endogenous protein production in the muscle, specifically for the Factor IX protein. Hemophilia B, affecting approximately 6,000 men in the U.S., results from a deficiency in the coagulation factor IX protein (FIX), which is crucial for blood clotting in the body. While current treatments involve frequent factor concentrates infusions, they fall short of providing a lasting solution. Gene editing, particularly CRISPR-Cas systems, holds potential but faces challenges due to the diversity of mutations underlying hemophilia B. Alternatively, delivering a complete factor IX gene offers a more comprehensive treatment approach, albeit with its own hurdles. Liver-specific gene therapies have shown promise but come with limitations, including immune reactions and liver health prerequisites. Instead of targeting the liver, some researchers have looked to other tissues and organs as delivery sites. Skeletal muscle has emerged as a compelling alternative due to its lesser regenerative capacity than the liver, its easy accessibility, and expression capabilities. My study focused on optimizing FIX production in skeletal muscle using various promoters and mutations.

I have been dedicated to this project for multiple years, during which time I have encountered many challenges. Despite my efforts, there were periods when it felt as though I was making no progress at all. It was disheartening to put in so much hard work and feel stuck, seeing no results. However, looking back, I realize that these struggles were part of the process, and even when progress wasn’t apparent, each step was bringing me closer to my goal. Through my work I have found that I am more resilient than I originally thought I was, and it also taught me to rely on other people more. I found a lot of support from the other undergraduate students and also from the graduate students in my lab. They helped me when I felt as if I was making no headway, both with research advice and my morale. I worked full time in the lab last summer, which was when I faced my toughest challenges in the project. I tried to clone a mutation into a plasmid sequence, but after two months of attempts, I still wasn’t able to induce the mutation. However, with the support of my coworkers, I was able to push through and come out stronger. After that and an internship at Arkansas Children’s Hospital Research Institute, I knew that a career in research would be the right direction for my future.