• Characterization of a Cyclic Peptide AD05 as a Novel Inhibitor of the Hsp90 Chaperoning Machine

      Fang, Wayne; Lu, Sumin; Jilani, Yasmeen; Debbab, Abdssamad; Chadli, Ahmed; Debbab, Abdssamad; Biological Sciences; Chadli, Ahmed; Augusta University; Heinrich Heine Universität Düsseldorf (1/31/2020)
      Protection of oncogenic proteins is the foundation of many hallmarks of cancer. Based on this, hsp90 inhibitors have emerged as a potentially potent strategy for cancer treatment. The clinical efficacy of the earlier Hsp90 inhibitors remains unsatisfactory, in part due to their induction of heat shock response and anti-apoptotic mechanisms in cancer cells. To identify alternative therapeutic agents without these effects, we have developed a cell-free high-throughput screen (HTS) platform based on the folding of progesterone receptor (PR) by the core components of the Hsp90 chaperoning machine. During our initial screening of 175 natural products from North African medicinal plants, we discovered the cyclic peptide AD05 as a novel Hsp90 inhibitor. AD05 has shown a powerful antitumor activity against various cancer cell lines including HeLa, Hs578T, MDA-MB231, MDA-MB453, E0771, THP1, and U937. Western blot analysis revealed that AD05 destabilizes Hsp90 client proteins without inducing heat shock response as indicated by lack of upregulation of Hsp70, Hsp40 and Hsp27. Remarkably, AD05 does not induce apoptosis but rather triggers autophagy in various cell lines.
    • Diagnosis of Mental Illness in the Narrator of Charlotte Gilman's "The Yellow Wallpaper" Using the DSM-5

      Fang, Wayne; Sadenwasser, Tim; Biological Sciences; English and Foreign Languages; Sadenwasser, Tim; Augusta University (12/10/2019)
      Charlotte Gilman's "The Yellow Wallpaper" explores mental illness, freedom, and the faults of the rest cure by exploring the life of a wife who has been diagnosed with neurasthenia. With this story Gilman describes an increasingly common practice during her time, and how problematic it was for the individuals who were diagnosed. Through the wife's narration, Gilman shows how many women felt trapped since they were forced to undertake the rest cure due to one-sided relationship dynamics. Using this narrative of the wife's deteriorating mental health, Gilman argues for equality in relationships as well as better treatments for mental health. In this presentation, I will use the Diagnostic and Statistics Manual of Mental Disorders (DSM-5) as well as other scholarly sources to diagnosis the wife's mental illness. To do this, I will take the wife's narration and compare it to diagnostic criteria as presented in the DSM-5. By examining the narrator's thoughts and actions I will be able to examine the progression of her mental illness. Examining the wife's mental health can show how many women of her may have felt trapped. This in turn can explain how many women faced unequal power dynamics in their marriages.