I entered the Rafferty lab at Kansas State University on a National Science Foundation funded program in the summer of 2016. My research embodied the work toward the total synthesis of natural products: uvaretin, c-benzylated chalcone, and lagunamide C. These molecules are desired due to their respective antineoplastic properties and each has an extensive and unique synthetic route which pose various challenges. Once a synthetic route to the chalcone core was established, a molecular library of uvaretin and chalcone derivatives were synthesized. The library is now undergoing rigorous potentiation testing. Synthetic efforts towards ladunamide C are still in progress. Through my research efforts, I was given the opportunity to present at numerous research forums including the National American Chemical Society meeting and have one accepted manuscript as primary author (Dallman et al., 2019), and one as a contributing author (Weeramange et al., 2019). Both papers illustrate the synthetic work toward uvaretin and the chalcones as well as these molecules’ ability to act as potentiators in cancer cells, such as pancreatic. Several known chemotherapeutic agents were potentiated with the chalcones in these manuscripts and the highlight of our findings illustrate the synergistic effects of the chalcones with 6-thiopurine. Though the mechanism behind this synergistic coupling is not fully understood we are hopeful that future experiments will exemplify the chalcone’s potentiation abilities. With an advanced mechanistic understanding of this potentiation, we will be able to expand the arsenal of chemotherapeutics and improve treatment efficacy.Weeramange, C., Lansakara, A., Dallman, J., Nguyen, T., Hulangamuwa, W., & Rafferty, R. J. (2019). MedChemComm, 717–725. https://doi.org/10.1039/c9md00010kDallman, J., Lansakara, A., Nguyen, T., Weeramange, C., Hulangamuwa, W.,& Rafferty, R. J. (2019). MedChemComm, Accepted Manuscript. https://doi.org/10.1039/C9MD00052F

While at St. Jude, I performed research under Dr. Mark Hatley in the Department of Oncology. My research project focused to identify genetic drivers which disrupt myogenic differentiation in children who develop rhabdomyosarcoma. In the lab, I performed genetic cloning procedures, viral transfections and transductions, and a variety of cell assays. I attended daily research and clinical lectures which highlight problems and solutions in modern cancer treatment. When not in lab, I spent time shadowing physicians in St. Jude’s operating room and oncologists at West Cancer Center. In my free time, I attended volunteer events at St. Jude’s provided housing complexes where I could interact with the kids. St. Jude provided me with a whole summer of medical experience which included witnessing clinical and municipal patient-provider interactions, shadowing physicians in the oncological field, and conducting biomedical research with translational implications. Spending a summer in a pediatric hospital gave me the daily opportunity to spectate pediatric physicians’ bedside manner. By observing interactions, I identified the significance of physicians displaying humanistic qualities for a successful relation and connection with the patient. These fortified patient-physician relationships help ensure patient compliance which is essential for patient well-being. The daily medical experiences and interactions acted as a daily inspiration to constantly look for ways to further the field of medicine both as a researcher and a future physician.

I accepted my second NSF-REU funded research position at the University of Puerto Rico for a summer appointment and shifted my focus to understanding the enzymatic mechanisms of cancer cells. I spent 10 weeks researching wildtype (wt) and mutant cytochrome c (cyt-c) proteins under Assistant Professor Dr. Marvin Bayro. Cyt-c is found in the mitochondria of cells and effects cancer cells by modulating the electron transport chain and the caspase-mediated apoptotic pathway. Studies have suggested that specific mutations in the protein could serve as a therapeutic anticancer target. We were interested in understanding the A43C mutant that has been found to exhibit superior caspase activation in vitro relative to the wt protein. We synthesized isotopically labeled proteins using enhanced media and E. Coli cells for multidimensional NMR spectroscopy measurements. We aimed to identify structural differences between A43C and wt cyt-c which may account for the enhanced activity. We found a higher degree of conformational flexibility in the A43C mutant, in addition to specific structural changes at the residue level. A manuscript highlighting the critical differences between the structural flexibility of mutant proteins and biological activity is in progress. I worked to optimize media dilutions, iron concentrations, and cellular light exposure to produce a robust amount of enzyme. During my time in Puerto Rico, I learned an entirely new array of laboratory techniques including cell culture, plasmid vector synthesis, and protein quantification via spectroscopy.Saxena, M., Dallman, J., Castaner, A., Bayro, M., & Griebenow, K. (2018). Solution NMR Study of a Cytochrome C Mutant(A44C) with Enhanced Apoptotic Activity. Biophysical Journal. 114. 573a. 10.1016/j.bpj.2017.11.3134.

“How to Succeed in Early Chemistry Classes” was an educational research project I conducted during the 2015-2016 academic year at Highland. Through the completion and analysis of student surveys at 7 institutions, I identified study habits and initiatives that successful students take while enrolled in a chemistry course. I presented my findings at the National American Chemical Society (ACS) Meeting in San Diego, CA, where I received “Best Overall Poster” in the Younger Chemistry Education Scholars Division.

I accepted my first paid research position under Associate Professor Dr. Justin Walensky at the University of Missouri through the Stevens’ Summer Fellowship Program in 2015. I worked to develop and optimize a synthetic route to a dithiocarbamate ligand. The ligand was used to test various coordination chemistry reactions. I spent my summer learning about laboratory safety, organic synthesis techniques, and the dynamics of an academic research lab. This experience acted as a stepping stone in my undergraduate research career and provided me with valuable insight in organic synthesis and coordination complexes within the human body.