Developing pancreatic cancer therapeutics in an undergraduate thesis may seem a tall order, but chemistry major, creative writing minor (at Bryn Mawr), and biochemistry concentrator Tomas Aramburu ’19 did not shy away from the challenge.
When asked about the inspiration for the project, he expressed a deft understanding of the stakes of his work and its potential impacts and benefits.
“Big picture, the inspiration for this project is the design of novel pancreatic cancer therapeutics,” he said. “Pancreatic cancer is a devastating condition and remains incredibly hard to treat, as available therapies are often very debilitating. Ultimately, my project aims to use computational approaches to design drugs that can effectively treat pancreatic cancer while limiting off-target interactions.”
It makes sense, then, that Aramburu’s thesis is one undergirded by multiple forms of collaboration, both within his lab at Haverford and between this lab and the Massachusetts General Hospital Cancer Center. He is quick to give credit to each of these sources, noting that the project would not have been possible without each and every contributor.
“The project started with Raul Mostoslavsky and his lab at the Massachusetts General Hospital Cancer Center,” he notes. “Last year, Bereket Gebregziabher ’18 and Jessica Koshinki ’18 launched a collaboration with the Mostoslavsky Lab. [Through this partnership] I learned that collaboration is an incredibly important asset,” he said. “A few times, our project hit obstacles without easy solutions. Luckily, we managed to find collaborators with the skillsets necessary to help us clear each new hurdle. Without the support of our collaborators, we would not have access to the tools that made this project possible. Cecilia Zhou ’19, Rebecca Seeley ’19, and Hassan Ahamed ’19 made it possible to have a project with so many moving parts. I am very grateful to have had the opportunity to work with this amazing group.”
How did your thesis advisor help you develop your topic, conduct your research, and/or interpret your results?
Dr. Robert L. Broadrup advised my thesis. Dr. Broadrup was instrumental in organizing this project and setting up important collaborations. Our work has gone all the way to Istanbul, where Dr. Broadrup presented our research at Sabanci University. That, for us, was a significant opportunity because he found a new collaborator that brought fresh eyes and some truly pivotal insight into what we were doing. Dr. Broadrup’s connections have provided top-of-the-line software tools and the expertise to overcome a number of challenges. He’s been extremely supportive of my computational work, even providing his office computer for my endeavors. In the lab, Dr. Broadrup directs the synthetic projects. I think we have a good setup: I focus on identifying promising molecules, Dr. Broadrup figures out how to make them. Furthermore, Dr. Broadrup has been an important mentor during my time at Haverford. I look forward to staying in touch and continuing to work on this project after graduation.
What did you learn from working on your thesis?
I learned quite a few new skills, particularly relevant to computational approaches to drug discovery. We can use computational tools to predict how a drug will behave. We can simulate the interactions of known inhibitors in the Lin28 protein [a protein pathway identified as a target for therapeutic approaches] and then use this understanding to design more potent compounds. But there is also a very practical side—we can predict properties, like toxicity and bioavailability, or determine whether a compound is synthetically feasible, before pouring any reagents into a flask. The ability to make predictions, based purely on a compound’s structure, saves time and resources. The methods follow an easily reproducible workflow, amenable to drug design initiatives for other diseases. Medicinal chemistry applies useful, multidisciplinary methods and I think our approach in this project outlines a realistic framework for an undergraduate research-oriented course.
What are your plans for the future?
Next year, I will be working at the Wistar Institute, applying computational and biochemistry approaches to a different drug-discovery project. My thesis has definitely prepared me for this upcoming experience as I will be using some of the same methods. I am excited to learn new techniques and contribute what I’ve learned so far. I’m not only passionate about the biochemistry of medicine, but also the clinical side. While there is so much to learn through research, I think ultimately I’ll be going to medical school.
“What They Learned” is a blog series exploring the thesis work of recent graduates.