“Where do I start?” That’s the first thought that entered my mind as I was sitting in at the Hive. The Hive is one of my favourite spots on campus, where you can always find me with a hot beverage, my headphones plugged in, and deep in thought about my current piece of work with my laptop open in front of me.
Let me introduce myself to the world of University of Surrey Blogs’ readers.
Hi, World, my name is Nilgun, but you can call me Nil. I have been at this university for quite a few years now and currently I am on my final year doing an Integrated Masters in Biochemistry (highly recommend it :)).
Now that the setting and the introduction are both established, let me tell you the story of my Research Project. But before I do so, please keep in mind, I am soo at the beginning of this journey and I am planning to take you with me (well as part of my assessment for a module, and I’m obligated to do so, but you get the idea)! I recommend you sit back with a cup of hot tea and enjoy the ride!
My supervisor is Dr. Lisi Meira and together with my colleague, Tom, we will be studying the stress responses in cancer cells. To be more precise, we will be looking at alkylation-induced damage to healthy and tumour cells, and study their responses. Of special interest are the pathways for DNA repair and Endoplasmic Reticulum (ER) stress. Wow those are some complicated sentences. Don’t be scared (I know I was), we will go over everything in a simplified way.
The purpose of cancer therapies is to induce DNA damage in order to kill tumour cells. A group of compounds called alkylating agents are amongst the most commonly used in chemotherapy. For the purpose of this research, in our laboratory, we will be studying the cellular response to alkylation-induced stress.
Dr. Lisi Meira and her colleagues pioneered work characterising the DNA repair enzyme alkyladenine glycosylase (AAG) revealing its importance on cancer induction as well as treatment. A surprising finding of their work was that AAG coordinates with other cellular mechanisms associated with the ER and protein damage/misfolding. This is an important detail because ER stress also has a profound effect on how cancer cells proliferate and survive in the body.
Seeing how AAG plays a critical role in cellular stress responses and the pathology of cancer, our current project aims to characterise this novel function of AAG, identify how the stress pathways “talk” to each other, and establish whether AAG cooperates with other proteins in the process.
Along the course of this research project, we will be using molecular and cellular techniques in order to examine stress response pathways that impact cancer development and treatment. We will also use different pharmacological modulators of stress, some of which have therapeutic potential, and assess whether they can interact with damaged DNA and increase cytotoxicity.
The importance of our work is to hopefully help the identification of novel therapeutic targets for cancer and/or adjust the currently available therapies so that patients get symptomatic relief and better treatment outcomes.
Thank you for taking time out of your day to read my first ever blog post!
Calvo, J., Moroski-Erkul, C., Lake, A., Eichinger, L., Shah, D., Jhun, I., Limsirichai, P., Bronson, R., Christiani, D., Meira, L. and Samson, L. (2013). Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1. PLoS Genetics, 9(4): e1003413.
Meira, L., Bugni, J., Green, S., Lee, C., Pang, B., Borenshtein, D., Rickman, B., Rogers, A., Moroski-Erkul, C., McFaline, J., Schauer, D., Dedon, P., Fox, J. and Samson, L. (2008). DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. Journal of Clinical Investigation, 118(7), pp.2516-2525.
Meira, L., Calvo, J., Shah, D., Klapacz, J., Moroski-Erkul, C., Bronson, R. and Samson, L. (2014). Repair of endogenous DNA base lesions modulate lifespan in mice. DNA Repair, 21, pp.78-86.
Meira, L., Moroski-Erkul, C., Green, S., Calvo, J., Bronson, R., Shah, D. and Samson, L. (2009). Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice. Proceedings of the National Academy of Sciences, 106(3), pp.888-893.
Wang, M., Wey, S., Zhang, Y., Ye, R. and Lee, A. (2009). Role of the Unfolded Protein Response Regulator GRP78/BiP in Development, Cancer, and Neurological Disorders. Antioxidants & Redox Signaling, 11(9), pp.2307-2316.
Yadav, R., Chae, S., Kim, H. and Chae, H. (2014). Endoplasmic Reticulum Stress and Cancer. Journal of Cancer Prevention, 19(2), pp.75-88.