Rebecca Chen
Please provide a brief summary of your research.
This summer, for my independent SURG research project, I worked in Dr. Atique Ahmed’s lab, which focuses on elucidating the mechanisms of therapeutic resistance in glioblastomas from the angles of cellular plasticity, stem cells, and epigenetics. By understanding the mechanisms of therapeutic resistance, the Ahmed Lab also is actively involved in the development of new brain cancer therapies to improve patient outcomes. Specifically, for my research project, I wanted to further understand the role of 2-HG, an oncometabolite, in the mechanisms of glioblastoma therapeutic resistance, specifically comparing the inhibition of TET2 by D-2-HG and L-2-HG, an enzyme critical for epigenetic modifications in brain cancer that could lead to therapeutic resistance. To elucidate the involvement of L-2-HG as an inhibitor of TET2 contributing to epigenetic modifications involved in TMZ resistance, my project sought to investigate the differences between the addition of L-2-HG and D-2-HG on the 5mC pathway and stemness. Given that glioblastoma remains a devastatingly incurable disease with a near 100% recurrence rate, investigating the mechanisms of therapeutic resistance may inform new glioblastoma treatments that extend patient life spans.
What made you initially interested in researching your project in particular?
In high school, I became really interested in the brain as a result of a cellular and molecular neuroscience course I took, as I was shocked by the complexity of the brain along with its both physical and non-physical nature. I was also struck by how much we didn’t know about the brain and the fact that many neurological diseases don’t have effective treatments and cures as a result of this. For example, over the last few decades, the prognosis of glioblastomas (GBM) has remained poor with only 5% of patients surviving 5 years post-diagnosis as a result of a near 100% universal recurrence rate for GBM. As a pre-med interested in neurosurgery and oncology, the Ahmed lab’s glioblastoma research immediately piqued my interest. Current research points to epigenetic modifications, such as DNA methylation, as one of the key mechanisms in therapeutic resistance. Thus, my graduate school mentor in the lab was working on a project regarding L-2-HG’s role in chemoresistance, so after undergoing training in relevant laboratory techniques, that inspired me to take on a new angle for my project, exploring L-2-HG’s inhibitory interaction with TET2.
What made you interested in pursuing (interdisciplinary) research more broadly?
I applied for SURG because I wanted the opportunity to take on an independent research project, where I would be able to gain invaluable experience in how to think scientifically, whether it be in the form of troubleshooting, data analysis, and experimental design. In my classes, I spent a lot of my time learning about all these neurological disorders and the cutting-edge research that was going on, and I knew I wanted to somehow be a part of that in the future. I also wanted to be able to try out the laboratory techniques I’ve seen in textbooks. I’ve always been someone who likes to take on challenges, and that’s why I decided to pursue research related to a disease that has kept physicians and researchers stumped for years. In the lab, I realized that research wasn’t something that’s individual—a lot of interdisciplinary is required. For example, for one of our experiments, we had to work with another department to complete it. I loved the idea of being part of a team that’s devoting their life to furthering our knowledge on the mission of improving the quality of life for patients and families everywhere. I also really enjoy problem-solving and critical thinking, and sometimes I just lay in bed at night thinking about the signaling pathway mechanisms and “what ifs.”
Describe your experiences with research thus far. Was it tricky? What skills do you think you’ve gained?
It was definitely really challenging at times, and although this was my own project, I received a lot of support from my mentors. I had to ask a lot of questions related to a variety of things, such as the optimization parameters for lab techniques, and my mentors’ experiences with creating a “scientific story.” I gained a lot of skills related to techniques, such as immunofluorescence microscopy and western blotting. However, what I found most rewarding was the problem-solving skills I gained. A lot of unexpected things happened, and I went through a lot of failures. But without these failures, I wouldn’t have learned as much as I did. I was also able to improve my communication skills through presenting at weekly lab meetings, and I’ve thoroughly experienced the importance of constructive feedback and collaboration. This summer has only affirmed my interest in pursuing research in the future.
Any tips or advice you have for students similar to you that are interested in pursuing undergraduate research?
Research can seem daunting at first, but you should never feel alone. If you want to get involved, I would encourage exploring your interests first and searching for faculty doing research that aligns with those interests. Aside from the Office of Undergraduate Research, I think talking to upperclassmen who have been involved in research throughout their undergraduate career is a great idea. Everyone I’ve met has been so nice and open to sharing their experiences. I think it’s also important to find a mentor who’s passionate about your success and has the capacity to help you gain a greater understanding. I think finding a lab that has experience with mentoring undergraduate students is super important. Cold-emailing may also seem scary at first because it seems like you don’t know anything, but I believe the most important thing is your interest and willingness to learn.