The Cecil H. and Ida Green Center for Systems Biology invites fellow scientists from other Institutions as well as from within UT Southwestern Medical Center to give seminars on the latest research.
Please visit UTSW Events and filter by channel Bioinformatics to see all upcoming events.
This Lecture Series is dedicated to highlighting the many facets of Systems Biology and its impact on biomedicine. It will feature key opinion leaders in this field and will be held four times a year.
Speaker: Timothy Mitchison, Ph.D.
When: 3/8/2022 at 4 PM Add to Outlook Calendar
Hosted by: Gaudenz Danuser, Ph.D.
How do microtubule drugs work as medicines?
Microtubules are dynamic protein fibers that transport vesicles in non-dividing cells and chromosomes during mitosis. Small molecule drugs that target microtubules, which are mostly plant-derived toxins, are important medicines. We know how they work at the molecular level, but not how they act therapeutically in the human body. Taxanes stabilize microtubules and are used to treat adult solid cancers. They block mitosis in cancer cells, but so do more recent drug candidates that failed in the clinic, so taxanes must have additional actions. We found that taxanes, alone among anti-mitotics tested in the clinic, cause chromatin bridges in post-mitotic cells. These activate the viral DNA sensor cGAS which triggers interferon secretion and might contributes to successful tumor regression. The ancient drug colchicine destabilizes microtubules and is used at low doses to treat gout and other inflammatory diseases. Using mouse disease models, we found that colchicine acts selectively in the liver to trigger release of anti-inflammatory hepatokines. These act on circulating myeloid cells to inhibit inflammation. Our unexpected findings that both taxanes and colchicine modulate inflammatory signaling illustrates the importance of these pathways in disease and therapy and has interesting implications for drug discovery and plant-derived traditional medicines.
Please email Prapti Mody if you encounter issues joining the meeting.