Early Effects

Pitt Group Uses PSC, XSEDE Resources to Learn Effects of Glucocorticoids on Embryonic Nerve Cells

April 7, 2016

Why It’s Important


Glucocorticoids have been a healing tool for treating allergies, asthma, autoimmune diseases and even some cancers. It’s a powerful family of medicines but can have strong side effects. In particular, scientists suspect the drugs may affect nerve-cell development. When pregnant women take these medicines, do they affect the embryos’ brain development? Could these effects cause lasting harm? Don DeFranco, Uma Chandran and their colleagues at the University of Pittsburgh, working with XSEDE Campus Champion Brian Couger at Oklahoma State University, investigated how a type of glucocorticoid called synthetic dexamethasone affects which genes are turned off and on in the stem cells that give rise to the nerve cells of the mouse hypothalamus. That’s the part of the brain that links with the hormonal system and affects development.

“Our partnership with PSC has been invaluable. We have biology and coding skills, but couldn’t have done this work without a powerful system like Blacklight, and now Bridges.” —Uma Chandran, University of Pittsburgh



How PSC and XSEDE Helped


The team analyzed which genes were active in the stem cells when the cells were and weren’t exposed to dexamethasone. They did this by isolating and sequencing the RNA created as active genes are directing the assembly of proteins. But the millions of RNA fragments they sequenced couldn’t be put into their proper order without supercomputing power. With Couger’s help and assistance from XSEDE ECSS member Phil Blood at PSC, the group used Blacklight, an XSEDE resource at PSC. Blacklight’s large shared memory was ideal for such big sequence-analysis problems.

The group identified a family of 200 to 300 genes that differ in activity between normal stem cells and those treated with dexamethasone—an important first clue. They also found a small difference in gene activity between stem cells from male and female embryos, hinting at possible sex-linked effects as well. They reported their results in the journal Molecular Endocrinology in January 2016. The team has since transferred their work from the now-retired Blacklight to PSC’s transitional Greenfield system, and will soon begin working on the new XSEDE resource at PSC, Bridges.