04 February, 2021
We are glad to have contributed to new work that challenges current paradigms of the etiology of lung squamous cell carcinoma (LUSC).Together with the team of Or Gozani at Stanford University, our close colleagues Lukasz and Mariusz Jaremko at KAUST and others, we found that a mutation in a histone H3K36 methyltransferase, NSD3 is a LUSC associated variant. The multidisciplinary team found that pathologic generation of H3K36me2 by mutant, hyperactive NSD3 rewires the chromatin landscape to promote oncogenic gene expression. Conversely, ablation of NSD3 attenuates tumor growth and extends survival in a potent LUSC mouse model. Dulat Azhibek in the lab contributed to the molecular and structural characterization of the newly identified NSD3 mutant, establishing essential substrates for NMR experiments and setting up binding studies with recombinant chromatin templates. We hope that the new work can define novel avenues of treating LUSC, a severe form of cancer.
Congratulations to all involved in the lab's latest publication in Nature. Read the full article here