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K-State Today

September 24, 2019

Philip Hardwidge to speak about developing drugs from bugs for autoimmune diseases on Sept. 25

Submitted by Biochemistry and Molecular Biophysics

Philip Hardwidge, professor of bacteriology in diagnostic medicine and pathobiology at K-State, is the featured speaker for Biochemistry and Molecular Biophysics Seminar on Wednesday, Sept. 25. He will present "Drugs from Bugs: leveraging bacterial virulence proteins to develop new anti-inflammatory compounds" at 4 p.m. in 120 Ackert Hall.

Presentation: Autoimmune or chronic inflammatory diseases such as psoriasis are caused by aberrant and overactive immune responses. While immunosuppressive drugs and various biologics have been used successfully to treat these disorders, many of these drugs have notable limitations, including systemic application, nonselective modes of action, adverse side effects, limited access to relevant sites of inflammation and high costs. Research into the molecular mechanisms by which pathogens have evolved to inhibit host immune responses has advanced the idea that microbial proteins can be used to treat chronic inflammatory or autoimmune diseases, the "Drugs from Bugs" concept. We have focused on several Yersinia enterocolitica and Escherichia coli "effector" proteins. Effectors are virulence proteins that are injected directly into infected host cells through a bacterial type III secretion system. We have achieved a mechanistic understanding of how these effectors suppress host immune responses in their targeting and inhibition of the regulatory components of the NF-B pathway. NF-B-dependent signaling leads to the induction of pro-inflammatory cytokines that contribute to psoriasis. We are developing a panel of recombinant effector proteins that we have engineered to penetrate human and mouse skin without the need for the original pathogenic bacterium. We have applied these proteins directly to relevant sites of inflammation and have achieved positive therapeutic outcomes in mouse models of chronic skin inflammation, without side-effects or the production of anti-effector antibodies. Hardwidge will discuss the biochemical activities of the effectors, our data from mouse models of psoriasis and keratinocyte cell culture experiments, and reinforce the concept that developing bacterial effector proteins into anti-inflammatory drugs will positively impact future translational approaches to treat psoriasis.

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