Dr. van Hoek’s bed bug collaborative research may yield alternatives to antibiotics.
George Mason University professor Ramin M. Hakami is searching for new ways to treat modern ailments by studying bacterial and viral biodefense agents, including the medieval disease notoriously known as the Black Death.
Read the press article: https://www2.gmu.edu/news/1924
Drs. Monique van Hoek and Barney Bishop were awarded a collaborative grant with James Madison University to study antimicrobial activity in the bedbug, Cimex lectularius.
Dr. Monique van Hoek is quoted in an article about peptides designed to break through bacteria walls.
“In the ongoing battle against emerging antibiotic resistant bacteria, antimicrobial peptides represent a potentially powerful new class of antibiotics,” says Monique van Hoek, who works on AMPs at George Mason University in the US.
Read the full article: https://www.chemistryworld.com/research/molecular-drill-bits-attack-tuberculosis/7187.article
Original embargoed version: https://www.acs.org/content/acs/en/pressroom/newsreleases/2014/march/fighting-antibiotic-resistance-with-molecular-drill-bits.html
The Kehn-Hall lab has been focusing heavily on the study of host-pathogen interactions of Rift Valley fever virus (RVFV). Recently, they demonstrated that the cellular antioxidant enzyme superoxide dismutase 1 (SOD1) is down regulated at early time points following exposure to RVFV. They provided evidence for extensive oxidative stress in RVFV infected cells. Concomitantly, there was an increase in the activation of the p38 MAPK stress response, which was regulated by the viral anti-apoptotic protein NSm. Alterations in the host protein SOD1 following RVFV infection appears to be an early event that occurs in multiple cell types. These data implies that maintaining oxidative homeostasis in the infected cells may play an important role in improving survival of infected cells. (Narayanan et al., Alteration in superoxide dismutase 1 causes oxidative stress and p38 MAPK activation following RVFV infection. 2011, PLoS One.6(5):e20354).
BRCA1 is a multifaceted tumor suppressor protein that has implications in processes such as cell cycle, transcription, DNA damage response and chromatin remodeling. The Kehn-Hall lab has demonstrated for the first time that BRCA1 is methylated both in breast cancer cell lines and breast cancer tumor samples at arginine and lysine residues. Arginine methylation by PRMT1 was observed in vitro and the region of BRCA1 504-802 shown to be highly methylated and the site of interaction. Inhibition of methylation resulted in decreased BRCA1 methylation and alteration of BRCA1 binding to promoters in vivo. Following methylation inhibition, Sp1 was found to preferentially associate with hypo-methylated BRCA1 and STAT1 was found to preferentially associate with hyper-methylated BRCA1. These results suggest that methylation may influence either the ability of BRCA1 to bind to specific promoters or protein-protein interactions which alters the recruitment of BRCA1 to these promoters. Thus, given the importance of BRCA1 to genomic stability, methylation of BRCA1 may ultimately affect the tumor suppressor ability of BRCA1. (Guendel et al. Methylation of the tumor suppressor protein, BRCA1, influences its transcriptional cofactor function. PLoS One. 2010 Jun 29;5(6):e11379).
As part of a continued search for more efficient anti-HIV-1 drugs, the Kehn-Hall lab is focusing on small molecule inhibitors that can efficiently inhibit HIV-1 replication through the restoration of p53 and p21WAF1 functions, which are inactivated by HIV-1 infection. They demonstrated that 9-aminoacridine (9AA) treatment inhibits HIV LTR transcription in a specific manner that was highly dependent on the presence and location of the amino moiety. Importantly, virus replication was found to be inhibited by 9AA in a dose-dependent manner without inhibiting cellular proliferation or inducing cell death. 9AA inhibited viral replication in both p53 wildtype and p53 mutant cells, indicating that there is another p53 independent factor that was critical for HIV inhibition. Furthermore, p21WAF1 was observed in complex with cyclin T1 and cdk9 in vitro, suggesting a direct role of p21WAF1 in HIV transcription inhibition. Finally, 9AA treatment resulted in loss of cdk9 from the viral promoter, providing one possible mechanism of transcriptional inhibition. Thus, 9AA treatment was highly efficient at reactivating the p53 – p21WAF1 pathway and consequently inhibiting HIV replication and transcription. (Guendel et al., 9-Aminoacridine inhibition of HIV-1 Tat dependent transcription. Virol J. 2009 Jul 24;6:114).
Dr. Kylene Kehn-Hall will receive the award from Vikas Chandhoke, Vice President for Research and Economic Development, at the Celebration of Achievements ceremony on be Monday, Nov. 11th in the Center for the Arts concert hall main lobby. The ceremony and reception will be from, 12:30 PM – 2:00 PM.
The winners’ short bios will be included in the Mason Research 2013 magazine that will be published in January.
Immobilised antimicrobial peptides damage E. coli cell membranes but leave human cells intact
By Michele McDonald
Flying in a small plane over Kenya 25 years ago, researcher Charlie Bailey searched for mosquito breeding grounds where he thought the virus that causes Rift Valley fever hid between outbreaks. He returned to Africa last month with better methods of diagnosing the devastating disease.