Our Research

Here in the Counter Lab, we are interested in exploring the following:

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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!

  • Li et al, Nat Rev Cancer 2018
  • Li et al, Nat Commun 2020
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WHY IS KRAS MUTATED SO OFTEN? 

Of the three RAS genes HRASNRAS, and KRAS, it is the latter that is found mutated more often.  We discovered that KRAS is 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!

  • Pershing et al, J Clin Res 2015
  • Ali et al., Nat Commun 2017
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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.

Check out these papers to learn more!

  • Kashatus et al, Nat Cell Biol 2011
  • Adhikari et al, Nat Commun 2018
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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!

  • Lim et al, Nature 2008
  • Brady et al, Nature 2014