The Effect of Anesthesia on Signal Transduction Pathways in Cells

The NF-kB inflammation pathway, the JNK cell proliferation and apoptosis pathway, andtheMerlin/NF2 cell growth pathways are essential in the regulation of virtually all major cellular functions and processes. However, little is known with regards to how the signaling scaffolding protein IKAP, a subunit of the Elongator complex, regulates these pathways, both with and without oxidative stress. When IKAP is mutated, its regulation of these pathways is dysfunctional, potentially causing neuronal degradation or death. When mutated IKAP iscombined with oxidative stress induced by anesthesia, these pathways are more upregulated, further harming the neuronal tissue. This studywill complete an in vitro investigation of the effects of a commonly employed dissociative anesthetic on cellular functions implicated in several phosphorylation signaling pathways. Data analysis and interpretation may elucidate new methods in preventing anesthesia-associated nerve damage in patients undergoing surgery.

I’m Sofie Strompf and this is my OSCAR URSP fall 2023 project. My research focuses on the effect of anesthesia on signal transduction pathways in cells. My mentor is Dr. Ali Andalibi, and I want to give special thanks to Dr. Marissa Howard, Purva Gade, Matthew Gadziala, Dr. Alessandra Luchini, and Dr. Lance Liotta. So, the Nuclear Factor Kappa-B inflammation pathway, JNK cell proliferation and apoptosis pathway and the merlin/neurofibromatosis-type 2 cell growth pathways are essential in the regulation of virtually all major cellular pathways. However, little is known with regards to how the signaling scaffolding protein IKAP regulates these pathways, both with and without oxidative stress. When IKAP is mutated, its regulation of these pathways is dysfunctional, which potentially causes neuronal degradation or even death. When mutated IKAP is combined with oxidative stress induced by anesthesia, these pathways are more upregulated, which further harms the neuronal tissue. My study will complete an in vitro investigation of the effects of a commonly employed dissociative anesthetic, ketamine, on cellular functions implicated in several phosphorylation signaling pathways. Data analysis and interpretation may elucidate new methods in preventing anesthesia-associated nerve damage in patients undergoing surgery. This semester, I specifically focused on learning skills and techniques that I need in order to work in biological research. I completed my research at the Institute for Advanced Biomedical Research on George Mason University’s Science and Technology campus. I worked in the Luchini Lab, as well as the Center for Applied Proteomics and Molecular Medicine. This semester, I also gained valuable certifications that I need in order to work in a laboratory setting safely. I also learned more, non-laboratory specific skills. I few things that I want to highlight are my learning of writing an IBC protocol, which was necessary in order to obtain the anesthetic that we are using in the next stage of research in the spring. Additionally, my knowledge in writing an abstract is important in grant proposal writing, as well as conference applications, so that I can continue my research, and share my research, in the future. So, what’s next? In the spring, I am going to continue my research with the OSCAR URSP program. Specifically, I will begin working with neuronal cell lines. Currently I am working with IOMM cell lines and next semester I’ll work with more complicated, more difficult cell lines. We’ll also begin working with the anesthetic and doing specific experimental research with that. We’ll complete data analysis and data interpretation, and I will share my research via conferences and a paper.