Geisinger Commonwealth School of Medicine professor published in prestigious journal

Paper identifies a mechanism that may lead to a potential drug target for endocrine-related diseases

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SCRANTON, PA (11/21/2017) Raj Kumar, Ph.D., a professor of biochemistry and the director of research at Geisinger Commonwealth School of Medicine (Geisinger Commonwealth), is the lead author of a research article published on Nov. 13 in the online journal, Scientific Reports. Scientific Reports is a sister publication of Nature.

The article, Site-specific phosphorylation regulates the structure and function of an intrinsically disordered domain of the glucocorticoid receptor, was co-authored by Shagufta H. Khan, laboratory manager of Geisinger Commonwealth's department of Basic Sciences and William A. McLaughlin, Ph.D., associate professor of computational biology.

The paper identifies a mechanism of activation of the glucocorticoid receptor (GR) that may lead to a potential drug target for endocrine-related diseases including certain kinds of breast and prostate cancers that fail to respond to traditional hormone-based treatments. Phosphorylation is a natural and necessary post-translational modification that proteins undergo to maintain their specific structure and functions under normal physiological conditions. In specific types of cancer cells - triple negative breast cancer (TNBC) and castration-resistant prostate cancer - higher expression and activity of GR have been associated with the growth and proliferation of these cells. Dr. Kumar's research suggests that inhibiting phosphorylation-induced GR activation process could stop or slow the growth of these cancers.

"Ours is a novel finding, which provides a potential biological target for TNBC and possibly other cancers" Dr. Kumar said. "The next step in our research is to test whether certain small molecules can inhibit site-specific GR phosphorylation. If they do, there may be a new drug target for TNBC and possibly castration-resistant prostate cancer, both of which presently have little treatment options available.
To read the paper, visit www.nature.com/articles/s41598-017-15549-5.