Timeframe: 2025 – 2027
Goal: Advance understanding of FLC’s unique tumor microenvironment
Principal Investigator: Praveen Sethupathy, PhD
Study overview: Through this grant, Praveen Sethupathy, PhD, of Cornell University plans to outline the “spatial transcriptomics” of FLC. Dr. Sethupathy’s lab has been a leader in functional genomic studies, especially for liver and gastro-intestinal cancers. His group has focused on understanding the drivers of FLC to identify new potential therapies, and has conducted several studies of genome organization, gene and protein expression and tumor metabolism in FLC cells.
This new study builds upon years of work the Sethupathy lab has already conducted in FLC transcriptomics – the analysis of all the RNA molecules produced in FLC tissue at a given time. In simple terms, transcriptomics identifies which genes are expressed in a cell and are being transformed into functional products like proteins. Transcriptomics provides a snapshot of gene activity and therefore bridges the gap between the genome (what can happen in a cell) and the proteome (what does happen – what proteins are produced). Studying transcriptomics in FLC can therefore provide valuable insights into the molecular mechanisms underlying tumor development, progression, and treatment resistance.
Most recently, the team completed an effort leveraging state-of-the-art genomic technology to understand the gene activity of FLC at a “single-cell” level. While the “single-cell” effort provided the highest-resolution molecular profile of FLC completed to date, its limitation was that the spatial location of different cell types was not preserved.
This “spatial transcriptomics” effort represents the next step in the continuum of work from the Sethupathy group – mapping RNA expression to specific locations of cells within tissues. Since biological functions depend on cell organization, understanding that spatial context is critical. This analysis should be especially useful to improving our understanding of FLC’s tumor microenvironment (TME), which is critically important to many ongoing research efforts. It could also help identify cell-to-cell communication pathways in FLC that could be exploited as drug targets.