Our Goal

Our goal in the Kota lab is to understand the pathophysiological role of microRNAs (miRNAs) in human diseases and gene therapy. The Kota lab focuses on understanding the pathophysiological role of miRNAs in disease mechanisms associated with advanced forms of human cancers, such as pancreatic and liver cancers, and exploring their therapeutic and biomarker potential. Our previous studies have provided evidence for miR-29a replacement as an efficacious anti-cancer therapeutic strategy for liver cancer (Kota et al., 2009 Cell).

Part of our lab research efforts are dedicated to study the role miR-29 in various etiologies associated with hepatocellular carcinoma (HCC) (Jones et al., 2018). A vast majority of our current research is focused on studying the role of miRNAs in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (Kota et al., 2017). We have laid much of the groundwork for the role of miR-29 in PDAC tumor-stromal biology and found a significant downregulation miR-29 in both stromal and cancer cells (Kwon et al., 2015, Kwon et al., 2016). Restored expression of miR-29 reduced stromal protein accumulation, cancer growth, and sensitized chemoresistant cancer cells to gemcitabine. Our global RNAseq analysis, identified novel miR-29 targets that regulates tumor-stromal immunity, extracellular matrix remodeling, epithelial-mesenchymal transition, and invasion/migration of cancer cells. Based on these preliminary results, we are setting the stage to identify and characterize critical miR-29 targets associated with PDAC tumor-stromal biology and evaluate in-vivo function and therapeutic use of miRNA-29 in clinically relevant pre-clinical mouse models.

Using wide variety of genetic, biochemical, cellular approaches and unique miR-29 knockout, orthotopic, genetically engineered pancreatic cancer mouse models, 2D/3D, microfluidic model systems, our laboratory seeks to gain deeper mechanistic insights into the role of miRNA-29 in the pancreatic cancer tumor microenvironment and exploit miR-29/targets therapeutic potential via pancreas-targeted intraductal gene delivery (Quirin et al. 2017). In proof-of principle studies, we have demonstrated that systemic delivery via adeno-associated virus (rAAV) of miR-29a, a miRNA whose expression is frequently lost in hepatocellular carcinoma (HCC), potently suppressed tumor progression in a mouse model of HCC. Importantly, off-target effects were not observed.

The ultimate goal of the Kota lab is to develop better treatment strategies for pancreatic and liver cancers and improve survival outcomes of affected patients.