Title of Research: Human pancreatic organoids to study the early events of pancreatic cancer
Additional Authors: J. Jiang; J. Bray; A. Gosling; L. da Silva; K. Rosenova Atanasova; R. Ratnayake; H. Hakimjavadi; S. Chamala; M. Campbell-Thompson; C. Li; H. Luesch; T. Schmittgen
Our lab has been studying the early events of pancreatic ductal adenocarcinoma (PDAC), acinar ductal metaplasia (ADM). We developed an in vitro assay to study ADM by culturing primary human pancreatic acinar cells. Culturing the acinar cells on an extracellular matrix for 6 days allows for transdifferentiation that mimics ADM. We have cultured 58 donor’s specimens (11 Blacks, 23 Non-White Hispanics and 24 Whites). Total RNA isolated from 14 donor’s pairs of the day 0 (acinar) and day 6 (ductal) cells was sequenced using whole transcriptome sequencing. Acinar-specific genes were downregulated in the samples from day 6 ADM while ductal-specific genes were upregulated. The expression of pancreatic cancer associated genes significantly correlated with the gene expression/activity observed in normal pancreas undergoing ADM. During our investigation of drugs that inhibit pancreatic ADM in mouse cultures, we identified two compounds, LLL12B and Trichostatin A (TSA) that effectively inhibit ADM and reverse this process. The ADM inhibition and reversal experiments were repeated using human tissues. Following 5 days of culture, ADM was reversed by 500 nM of LLL12B and TSA. Our initial results suggest that Blacks who are also diabetics have less of a tendency to reverse ADM with the compounds.
About the author
Corey Perkins is a second-year PhD student in the department of pharmaceutics workingunder the supervision of Thomas D. Schmittgen. She received her bachelor’s in chemistry from the University of Delaware in 2019and began her graduate workin summer of 2019.Her research is focused on studying the earliest known precursor of pancreaticductaladenocarcinoma, acinar to ductal metaplasia. Her recent work consists of using novel compounds, such as LLL12B, a STAT3 inhibitor, and Trichostatin A, an HDAC inhibitor, to reverse acinar ductal metaplasia from human donors. With another aim of her research being the investigation of racial health disparities, she co-authored a paper to emphasize the need for greaterrepresentation of Black/African American samples in tissue biobanks. Corey is also a McKnight doctoral fellow and received partial funding from theU54 Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center.