Development of a healthy pancreas model for environmental pollutants testing and drug discovery

I have worked on developing a pancreatic microfluidic platform that mimics the human pancreas. A healthy microfluidic device for the pancreas is difficult to synthesize because pancreas is a secretory organ and the digestive enzymes it secretes make it difficult for such a platform to exist. In this research, I have worked around that limitation by using a re-engineered pancreatic cancer cell line where a cellular homeostatic regulator Pancreatic Transcription Factor 1 subunit alpha (PTF1a) is induced. The induction of PTF1a helped change the cancerous cell line to a more normal-like one. These properties helped us synthesize a Pancreatic Organ-on-a-chip (OOC) platform that mimics pancreas.

The Pancreatic OOC platform was further used and can be described in two main sections, firstly we have utilized the OOC platform to study pancreatic tumorigenesis of an environmental pollutant called Perfluorooctanoic acid (PFOA) which is a member of larger Per-fluoro and poly-fluoroalkyl substances (PFAS) family. PFOA is one of the contaminants that is largely non-biodegradable and cannot be metabolized by most biological processes. Hence, PFOA accumulates in biological systems and is hypothesized to cause many serious illnesses including pancreatic cancer. I have utilized our Pancreatic Organ-on-a-chip (OOC) platform to study if the PFOA plays a role in inducing cancer-related pathways in humans.

In the second part, I investigated the effects of PTF1a induction on multiple PDAC cancer cell lines to study the viability of a gene therapy drug that might be instrumental against pancreatic cancer. This therapy is largely based on the reintroduction of PTF1a which plays a key role in establishing cellular homeostasis in the adult pancreas. In neo-natal stage it plays the central role of directing the differentiation of various germ cells in pancreas. I have worked on developing PTF1a mRNA and have delivered it to three pancreatic epithelial cell lines. I have studied the effects that PTF1a has on these cell lines using RT-qPCR to establish the key genetic changes. Overall, I have worked on the development of an artificial pancreas model and have used it to study the effects of a common environmental pollutant and have worked in the drug discovery area for pancreatic cancer.