Autophagy Impact in Pancreatic Cancer Cells and Therapeutic Effect on Cardiotoxicity
Supervised By: Howard Chen, Chen's Lab at the Molecular Cardiology Research Institute (MCRI)
Project Background
I am always fascinated about how biological and biotechnological research advance medicine. I first contacted Dr. Howard Chen in October 2022 to learn about his lab’s expertise in molecular imaging technology and the application of imaging processes in cells can inform about disease and the response to therapy. Building upon my course work as a Biology and Biotechnology major, I will be working with Doctor Chen at his lab in Tufts Medical Center studying the role of autophagy in pancreatic cancer cells and the therapeutic effect on cardiotoxicity.
Autophagy is a conserved catabolic process where cells recycle part of the cytoplasm during stress. It is still uncertain whether autophagy plays a protective or detrimental pathophysiological role on cell function in the heart and in cancer cells. My proposed research will focus on pancreatic cancer, a devastating cancer that has the highest mortality rate and only 11% of 5-year relative survival rate. Specifically my research will be investigating what impact autophagy plays in pancreatic cancer cells and in the heart when exposed to drugs that are in clinical use.
Pancreatic cancer is typically treated with chemotherapy drugs–Gemcitabine (Gemzar) 5-fluorouracil (5-FU) Irinotecan (Camptosar)- all taken in conjunction with each other. The effects of these drugs on cardiotoxicity have been studied and shown to cause a damaging increase of toxins to the heart, resulting in myocardial infarctions. A new antipsychotic drug, pimavanserin, has been in trial for its novel anticancer potential in pancreatic cancer, however, there is little research on its impact on cardiotoxicity, thus its full effects are still unknown. Interestingly, recent research demonstrated that pimavanserin kills cancer cells via activating autophagy leading to cancer cell apoptosis. Using a novel cardiac slicing culture that Dr. Chen’s lab recently developed, I will investigate the effect of pimavanserin on pancreatic cancer cells and in the heart. I will further perform co-culture experiments of pancreatic cancer cells and cardiac slices and assess the impact of pimavanserin on cancer cell killing and cardiotoxicity risk in this experimental system. My hypothesis is that unlike in the case of the 3-drug combination therapy, the new drug pimavanserin that activate autophagy and drives cancer cells towards apoptosis may induce beneficial autophagy in cardiac slices thus free from potential cardiotoxicity and safe to use in humans to treat pancreatic cancer.
Overall, from the experience, I aim to gain a deeper understanding of the scientific processes and how to effectively learn to synthesize, analyze, and communicate complex findings. I hope to gain a better understanding of what it requires to effectively and successfully perform scientific research. In addition, I aspire to gain more confidence in my own knowledge and develop more leadership qualities.