Here in the Counter Lab, we are interested in exploring the following:
HOW DOES CANCER BEGIN?
The RAS genes are mutated in upwards of a third of human cancers. Interestingly, the particular family member, position, and substitution of RAS mutations exhibit a distinct pattern for each cancer. As these are often extremely early mutations, these patterns reflect the process of how cancer initiation. The lab uses cutting-edge sequencing platforms to dissect the factors that mold the mutational patterns of RAS genes.
Check out these papers to learn more!
RAS GENES AND CODON USAGE.
The RAS family is comprised of three genes, HRAS, NRAS, and KRAS. While the proteins are nearly identical, we found that the genes differ in their codon usage, with KRAS being enriched in rare codons that reduce protein expression. The lab explores the effect of manipulating codon usage of RAS genes on tumorigenesis.
Check out these papers to learn more!
HOW DOES RAS SIGNAL?
As RAS proteins exert their oncogenic signaling by engaging other proteins. The lab using innovative technologies like proximity-labeling coupled to CRISPR/Cas9 screens to identify potential new therapeutic targets mediating RAS oncogenesis.
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TRANSLATING IDEAS INTO INHIBITORS
As new modifiers of oncogenic RAS signaling are identified the lab develops pharmacologic approaches to target these proteins. This can be through repurposing existing inhibitors or developing new compounds. Some examples of this include copper chelators to inhibit MEK kinases or nitric oxide inhibitors to suppress tumor maintenance.
Check out these papers to learn more!