Fellow: Donald Long

Mentor: Praveen Sethupathy

DESCRIPTION (provided by applicant): 

Fibrolamellar carcinoma (FLC) is a unique, rare liver cancer that usually occurs in young individuals. Currently, there is no standard of care for this disease, and the molecular underpinnings of the unique cancer are still largely unknown. At the molecular level, what first set FLC apart is an in-frame fusion of parts of two genes, DNAJB1 and PRKACA. The Sethupathy lab revealed dramatic reconfiguration of chromatin activity in FLC, ultimately leading to new patterns of transcription genome-wide. Some of these newly active loci include genes that are associated with super enhancers, which are known to mark genes critical for tumor cell behavior. SLC16A14 is associated with one of the strongest FLC-specific super enhancers, and is among the top-most aberrantly upregulated genes in FLC at the level of nascent transcript, steady state mRNA, and protein. Additionally, I have shown that SLC16A14 knockdown significantly reduces cell viability in our human primary cell model of FLC. SLC16A14 is an orphan transporter about which very little is known in human biology or disease pathology. Based on all of the exciting preliminary data, I hypothesize that SLC16A14 is critical for FLC cell viability and/or growth. I will set out to 1) determine whether SLC16A14 is linked to FLC survival/growth and 2) define the specific role of the SLC16A14 protein in energy metabolism in this cancer. Successful completion of my aims will reveal novel molecular insights into a poorly understood cancer and potentially uncover a novel therapeutic strategy, which is sorely needed for this devastating cancer.