Taking on Pancreatic Cancer

What biomedical issues captured your curiosity, and what did your studies find?

Pancreatic cancer is scientifically intriguing to me because it is so different from other cancers. It’s among the most severe malignancies, with dismal survival rates. It’s tough to diagnose because primary tumors are small and hard to detect, and drugs that work against other cancers often fail to treat it.

My research focused on the epigenomic landscape of pancreatic cancer and its effect on gene expression, which may alter how tumors respond to treatment. In particular, we were interested in an enzyme, histone methyltransferase KMT2D, that is known to regulate the expression of genes. We found that KMT2D was highly mutated and expressed in lower levels in pancreatic cancer patients, so we investigated the effect of the loss of KMT2D in pancreatic cancer biology.

We found that the loss of KMT2D in preclinical models of disease resulted in a rapid progression of cancer and a drastic reduction in survival. With RNA sequencing we assessed how the loss of KMT2D affects gene expression. Our studies found an increase in the expression of genes associated with drug metabolism, so we used a large-scale screen to investigate multiple chemotherapeutic agents and evaluate drug response. Interestingly, we found that the loss of KMT2D led to a resistance to the drug 5-fluorouracil, known as 5-FU, which happens to be one of the main chemotherapies used to treat pancreatic cancer. Our work has highlighted that there may be a subset of pancreatic cancer patients who do not respond to 5-FU treatment because of mutations they harbor in KMT2D. Our results may eventually help doctors tailor treatment for patients with those mutations.

What opportunities at Mayo did you take advantage of to further your leadership skills and your career? 

I served as a teaching assistant for multiple courses in the graduate school, which was a great learning experience. I honed my skills in mentorship and management. I got to critically review course content and learn more myself. On a personal level, I loved interacting with students and guiding them through graduate school, and I had the opportunity to meet friends (and future colleagues!) who have a breadth of experience and come from highly varied backgrounds.

How did your work with your advisor help shape you as a scientific thinker?

I met my thesis advisor, Dr. Fernandez-Zapico, through a graduate course he taught, and I was inspired by his passion for pancreatic cancer research. He always correlated what we did with the real world, and his passion stemmed from his desire to help patients. The aspiration to help resonated with me on a personal level. It guided us when we designed our research projects, as we always took into consideration how our findings will further the field and how they will address the challenges patients face. I will take that approach with me. In my next career step, I will be a postdoctoral scientist at Karolinska Institute in Stockholm, Sweden, and will continue to work on cancer research, studying mechanisms of drug resistance.