Current Graduate Students in Comparative and Molecular Biosciences

Marissa Oram

[email protected]

Degree
B.A., Chemistry, College of St. Benedict

Advisor
Dr. Anja-Katrin Bielinsky

Research
During carcinogenesis, cells proliferate quickly and evade inhibitory regulation signals to support the growth of a solid tumor. This uncontrollable cell division compromises the fidelity of DNA replication, a phenomenon referred to as “replication stress” and an important hallmark of all cancer types. Epithelial cells that form the inner layer of the intestine are rapidly renewing tissues that can give rise to colorectal cancer, which is the third leading cause of cancer-related deaths in the US. Therefore, a better understanding of how cell division is dysregulated is particularly important for this cancer subtype. Our group has used the deficiency of an essential replication factor, minichromosome maintenance protein 10 (MCM10), as a model for chronic replication stress in human colon cancer cells. My dissertation research suggests that these cells rely on an important protein, RING finger protein 4 (RNF4), for survival. Without RNF4, MCM10 mutants do not duplicate all of their DNA, leaving some regions under-replicated. This exposed DNA is prone to damage, which accumulates, and results in cell death. Thus, the interaction between MCM10 and RNF4 can be exploited to kill cancer cells. In order to devise such therapies, we need to understand RNF4’s function which is the upmost goal of my dissertation research. We hypothesize that RNF4 prevents abnormally fast replication, and this is what I am currently investigating. This research will not only advance therapeutic intervention strategies for colon or other epithelial cancers but can broadly apply to all cancer types where DNA replication is commonly dysregulated.  

Publications
Baxley, R.M., Leung, W., Schmit, M.M., Matson, J.P., Yin, L., Oram, M.K., Wang, L., Taylor, J., Hedberg, J., Rogers, C.B., Harvey, A.J., Basu, D., Taylor, J., Pagnamenta, A., Dreau, H., Craft, J., Ormondroyd, E., Watkins, H., Hedrickson, E.A., Mace, E.M., Orange, J.S., Aihara, H., Stewart, G.S., Blair, E., Cook, J.G., & Bielinsky, A.K. (2021). Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening. Nature Communications, 12, 1626. https://doi.org/10.1038/s41467-021-21878-x.

Chang, Y.C.*, Oram, M.K.*, and Bielinsky, A.K. (2021, April). SUMO-targeted ubiquitin ligases and their functions in maintaining genome stability. Manuscript submitted to International Journal of Molecular Sciences. *These authors contributed equally

Peterson, L., Oram, M.K., Flavin, M., Seabloom, D., Smith, W., O'Sullivan, M. G., Vevang, K., Upadhyaya, P., Stornetta, A., Floeder, A., Ho, Y., Zhang, L., Hecht, S., Balbo, S., & Wiedmann, T. (2021) Co-exposure to inhaled aldehydes or carbon dioxide enhances the carcinogenic properties of the tobacco specific nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in the A/J mouse lung. Manuscript accepted for publication in Chemical Research in Toxicology.