Our new review on DNA repair, cancer and aging is out. Here we revisit the processes involved in DNA damage repair and how these can contribute to diseases. We discuss the use of PARP inhibitors in the clinic for the treatment of breast and ovarian cancer and the challenges associated with acquired drug resistance and how DNA repair pathway targeted therapeutics are moving beyond PARP inhibition. Kudos to @ThomasLClarke for the fantastic work!!!
Redefining Warburg!! Really happy our paper with Carlos Sebastian (@CSebastianLab) is out (it took a long journey!). We find that within tumors, non-dividing cells are the ones doing Warburg, basically challenging the dogma that this metabolic adaptation is for biomass.
What a fantastic way to end the year! We are very pleased to share that our latest paper is out at Cell Reports. Here, Barbara M. Pastor and Giórgia Silveira (@giorgiasilveira) present you with a GOF chromatin library developed and successfully employed in two complementary screens to uncover i. Proteins that affect kinetics of DNA repair and ii. Factors recruited and excluded from sites of DNA damage. We also describe, as proof of principle, PHF20, a novel factor that competes with 53BP1 for the H4K20me2 modification and is important for genome stability.
Happy to see our latest paper out! In this great collaborative work, Jee-Eun Choi et al. show that glycolysis is a main driver in squamous cells carcinoma, with Sirt6 acting as a potent tumor suppressor in these tumors. We also identify a subset of highly glycolytic tumor-propagating cells (TPCs) with increased antioxidant capacity. More importantly, we identify a subset of TPCs as the cell of origin for the Warburg effect, defining metabolism as a key feature of intra-tumor heterogeneity.
Congratulations to Samantha Linder, who defended her Ph.D. Thesis in an outstanding way!! AND became a mom the same week!! A lot to celebrate!!!
The Mostoslavsky lab is happy to announce that our incredible PI has just been appointed as full professor at Harvard Medical School. This is a testament to his love of his trainees and science. No one is more deserving – Congratulations Raul!!
In this work published in Molecular Cell, Etchegaray et al. characterized the histone deacetylase SIRT6 as a critical modulator of transcriptional pausing/elongation. Such a unique role for an HDAC may allow SIRT6 to fine-tune gene expression, to control expression of metabolic, developmental and ribosomal genes.
In this work, Christina Ferrer et al. identified a single homozygous amino acid change in the NAD+ binding domain of SIRT6, that results in perinatal developmental defects and eventually fetal demise due to an inability to silence pluripotent gene expression. This study provides the first evidence of chromatin modifiers directly contributing to human perinatal development and lethality, via the histone deacetylase SIRT6.
The year started well in the lab with five (!!) of our lab members receiving prestigious fellowships! And we celebrated the best way we know – with food! Congratulations Christina Ferrer for the Tosteson and ACS Postdoctoral Fellowships! Ruben Boon for the Human Frontier Postdoctoral Fellowship and Jordan Todd for the Ford Foundation Predoctoral Fellowship! Giórgia Silveira for the MGH Cancer Center Excellence award fellowship and Yasmin Hernandez-Barco for the Andrew L. Warshaw Institute for Pancreatic Cancer Research Award. We are all happy to see your talents being recognized! Well done!