During tumor formation neoplastic cells must adapt to a variety of cellular stresses, including low oxygen and nutrient deprivation.  The Gardner lab studies how cells adapt to these stresses. Ultimately the goal is to disrupt these adaptive mechanisms for therapeutic gain. They have demonstrated that nonsense mediated RNA decay (NMD), previously thought to be a constitutive mechanism to degrade mutated mRNAs, is in fact regulated by cellular stress. The inhibition of NMD upregulates select mRNAs and alternatively spliced mRNAs which play important roles in cancer. Furthermore, the lab has demonstrated that this novel mechanism of gene regulation augments several cellular stress responses, including the unfolded (integrated) protein response, autophagy, amino acid transport and glycolytic metabolism. They have shown that the inhibition of NMD contributes to cellular adaptation to stress, and critically contributes to three dimensional tumor growth.