Splice variants of KRAS
Until our recent report on the regulation of HK1 by KRAS4A (Amendola et al., Nature 2019), little was known about the differential function of the evolutionarily conserved alternative splice forms of the KRAS locus and KRAS4A was considered a relatively unimportant “minor” variant. We now seek to understand the differential biology of the KRAS splice variants. To do this we are using splice variant deficient mice in collaboration with Alan Balmain (UCSF) and building a novel GEMM with Kevin Haigis (Dana Farber Cancer Center). We are studying the relative expression of the splice variants in tumors as well as the regulation of alternative splicing. In collaboration with Itai Yanai (NYU), a pioneer in the field of single cell RNA sequencing, we are developing novel methods to utilize this technology to quantify splice variant expression in human tumors to explore the heterogeneity of expression.
