New findings in cancer research: Structure of Med-PIC, the fine control of gene expression, and more

TheoryLab

In this episode—which is for a scientific audience until the 27-minute mark—a current American Cancer Society grantee and a former grantee spoke with each other about their recently published new findings in cancer research. Alessandro Gardini, PhD, an Assistant Professor at The Wistar Institute, studies the epigenetic control of transcription during cell differentiation and oncogenesis. He recently published work in Cell titled “The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer:” https://pubmed.ncbi.nlm.nih.gov/34004147/. Yuan He, PhD, is Assistant Professor (but just received word that he’s being promoted to Associate Professor!!) at Northwestern University. The He lab The He lab uses cryo-electron microscopy (cryo-EM) and other biophysical and biochemical approaches to understand “the molecular mechanisms by which large, multi-subunit complexes engage in DNA-centric processes.” Dr. He recently published findings in Science on, “Structure of the human Mediator-bound transcription preinitiation complex:” https://science.sciencemag.org/content/372/6537/52. 4:12 – Dr. Gardini describes his new paper: “what we found is that when you combine CDK9 inhibition with activation by small molecules of the PP2A phosphatase…we get a much better block on transcription in these tumors…” 9:10 – Interesting question from Dr. He on the mysterious integrator complex 11:11 – “What do you think about this tug of war of the phosphatase competing with CDKs…?” 14:19 – Dr. He shared takeaways from his new paper: “And this eventually allowed us to build a model of how this gigantic 57-sub-unit machinery recognized CTD from the polymerase…” 19:11 – Dr. Gardini professes his love for CTD 20:39 – “What do you think is the threshold of phosphorylation in order for the mediator to start losing affinity…?” 25:36 – “Could we possibly think that both mediator and integrator are actually bound to non-phosphorylated CTD at the same time or could there actually be competition…?” 27:46 – Why is this work important? Why should a cancer patient, survivor, or caregiver be excited about these publications?