Email: support@essaywriterpros.com
Call Us: US - +1 845 478 5244 | UK - +44 20 7193 7850 | AUS - +61 2 8005 4826

novel technology molecular chaperones

Dr. Chadli’s laboratory focuses on understanding the Dr. Chadli’s laboratory focuses on understanding the biology and clinical implications of molecular chaperones, focusing specifically on the Hsp90 machine. A few years ago, they identified the UNC45A cochaperone as an important regulator of the progesterone receptor (PR) chaperoning and transcriptional activity. Recent studies have shown that UNC45A is essential for cancer cell proliferation. Silencing UNC45A inhibits cancer cell division through interfering with centrosomal function. UNC45A localizes to centrosomes and has been shown to be essential for tethering the kinase ChK1 to the centrosome. Loss of UNC45A significantly reduces the phosphorylation of ChK1 at S345, which is required for ChK1 centrosomal localization (Cancer Lett. 2015, 357:114-20). To identify novel inhibitors of the Hsp90 machine, the Chadli Laboratory has developed a high throughput screen (HTS) based on the PR using Rabbit Reticulocyte Lysate (RRL). The assay measures the recovery of hormone binding activities of PR after mild heat treatment. This novel technology will likely have a significant impact on Hsp90 machine-targeted drug discovery, and thus a broad impact on human health (J Biomol Screen. 2015, 20:223-9). Approximately 175 natural products from North Africa (Morocco) were screened in collaboration with Drs. A. Debbab and P. Proksch (Institute of Pharmaceutical Biology and Biotechnology, Düsseldorf, Germany). As a result, the bioactive metabolite sclerotiorin was identified, which inhibits the Hsp90 machine (Bioorg Med Chem. 2015, 23:126-31). In collaboration with Dr. David Fulton at GRU, Dr. Chadli’s group has shown that Nox5 stability and superoxide production is regulated by C-terminal binding of Hsp90 and CO-chaperones in a similar manner to the regulation of steroid receptor complexes. (Free Radic Biol Med. 2015, 89:793-805). chaperones, focusing specifically on the Hsp90 machine. A few years ago, they identified the UNC45A cochaperone as an important regulator of the progesterone receptor (PR) chaperoning and transcriptional activity. Recent studies have shown that UNC45A is essential for cancer cell proliferation. Silencing UNC45A inhibits cancer cell division through interfering with centrosomal function. UNC45A localizes to centrosomes and has been shown to be essential for tethering the kinase ChK1 to the centrosome. Loss of UNC45A significantly reduces the phosphorylation of ChK1 at S345, which is required for ChK1 centrosomal localization (Cancer Lett. 2015, 357:114-20). To identify novel inhibitors of the Hsp90 machine, the Chadli Laboratory has developed a high throughput screen (HTS) based on the PR using Rabbit Reticulocyte Lysate (RRL). The assay measures the recovery of hormone binding activities of PR after mild heat treatment. This novel technology will likely have a significant impact on Hsp90 machine-targeted drug discovery, and thus a broad impact on human health (J Biomol Screen. 2015, 20:223-9). Approximately 175 natural products from North Africa (Morocco) were screened in collaboration with Drs. A. Debbab and P. Proksch (Institute of Pharmaceutical Biology and Biotechnology, Düsseldorf, Germany). As a result, the bioactive metabolite sclerotiorin was identified, which inhibits the Hsp90 machine (Bioorg Med Chem. 2015, 23:126-31). In collaboration with Dr. David Fulton at GRU, Dr. Chadli’s group has shown that Nox5 stability and superoxide production is regulated by C-terminal binding of Hsp90 and CO-chaperones in a similar manner to the regulation of steroid receptor complexes. (Free Radic Biol Med. 2015, 89:793-805).