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Multi-Drug Resistant bacteria killed by Alligator antimicrobial peptides

Dr. van Hoek and research associate Stephanie Barksdale published a paper in January 2017 in Developmental and Comparative Immunology, “Cathelicidin antimicrobial peptide from Alligator mississippiensis has antimicrobial activity against multi-drug resistant Acinetobacter baumannii and Klebsiella pneumoniae.” In this paper, Dr. van Hoek and her team describe a powerful cathelicidin peptide from the American alligator. This antimicrobial peptide and fragments have very strong activity against a number of Gram-negative bacteria, including multi-drug resistant strains. Experiments indicate that these peptides work by punching very small holes in the bacterial membrane; however, these peptides do not do the same to mammalian cells.

To Read the Full Article Click here:     http://www.sciencedirect.com/science/article/pii/S0145305X16304293?via%3Dihub 

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Phage Wars: NIH grant awarded to Dr. Hakami

A NIH grant was award to Dr. Hakami in 2017 for development of a novel and highly promising phage-based therapeutic strategy to treat bacterial infections. For a GMU press release and article on this award, please visit https://www2.gmu.edu/news/488311

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Tasso, Ceres Nanosciences, George Mason University, and the United States Army Medical Research Institute of Infectious Diseases receive $4.25M to develop a universal surveillance platform for infectious disease outbreaks.

MANASSAS, Va. — September 28, 2017 — Tasso, Inc. (Tasso), Ceres Nanosciences (Ceres), George Mason University (Mason), and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) today announced the commencement of a $11.7 million program, funded by the Defense Threat Reduction Agency (DTRA), to develop a reliable, safe, and simple universal surveillance platform for infectious disease outbreaks.

Read the press article: http://www.ceresnano.com/press

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Mosquitoes take on rabbit fever and win

Researchers at George Mason who are investigating potential new sources of antibiotics are looking at unlikely sources including alligator blood and mosquitoes, said Monique van Hoek, a professor in Mason’s School of Systems Biology and at the National Center for Biodefense and Infectious Diseases.

Read the full article: https://www2.gmu.edu/news/253116

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Gator Blood Contains Naturally Strong Germ Fighters

Sophisticated germ fighters found in alligator blood may help future soldiers in the field fend off infection, according to new research by George Mason University.

Read the press article: https://www2.gmu.edu/news/1455

Read the journal publication: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117394

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New Study: Cranberries Pack a Punch to Bacteria Linked to Cystic Fibrosis

George Mason researchers are seeking out naturally based remedies to beat back antibiotic-resistant bacteria—and finding success.

Read the press article: https://www2.gmu.edu/news/1457

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International Research Team Tackles Deadly Virus

A George Mason University-led team of international researchers is looking for ways to treat a debilitating and often fatal encephalitis virus that hits horses and humans alike.

Read the press article: https://www2.gmu.edu/news/1757

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Dr. Hakami is awarded USAMRIID contract

The U.S. Medical Research Institute of lnfectious Diseases (USAMRIID) has announced intentions to award a new contract to Dr. Hakami of George Mason University for profiling of host responses to high priority pathogens.

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Governor Terry McAuliffe visits

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Bugged Out: Bed Bugs Could Be Key in Development of New Antibiotics

Dr. van Hoek’s bed bug collaborative research may yield alternatives to antibiotics.

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Mason Researchers Looking for Fresh Answers in a Medieval Disease

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

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Dr. Van Hoek and Barney Bishop – Mason 4-VA Grant Awards Honored

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.

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Molecular drill bits attack tuberculosis

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

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Updates from the lab of Kylene Kehn-Hall, PhD

Some of the latest findings from the Kehn-Hall lab during the past two years include:

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).

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Dr. Kylene Kehn-Hall 2013 Mason Emerging Researcher Award

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.

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Expert commentary

Expert Commentary: Could wasp venom peptide keep catheters sterile?

Immobilised antimicrobial peptides damage E. coli cell membranes but leave human cells intact

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Researcher Returns to Africa with New Way to “Trap” Deadly Virus

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.

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Dr. van Hoek receives 2013 OSCAR Mentoring Excellence Award

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Dr. van Hoek gives a 2013 TEDx Talk

Dr. van Hoek gives a TEDxGeorgeMasonU talk on April 6, 2013.

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Drs. Kehn-Hall and Carpenter have received a contract from Unither Virology

Dr. Kehn-Hall and Dr. Carpenter have received a contract from Unither Virology entitled “Animal Modeling Development and Therapeutic Testing”.  This contract will focus on the development of an aerosol exposure mouse model of Venezuelan Equine Encephalitis Virus.

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Dr. Kehn-Hall has received a subcontract from Ceres Nanosciences to facilitate work on a DARPA project

Dr. Kehn-Hall has received a subcontract from Ceres Nanosciences to facilitate work on a DARPA project entitled “Universal Nanotrap-enabled Biofluid Sample Preparation and Storage Toolset”. This is a two year grant that is focused on testing whole virus capture and preservation with NanoTrap particles both in liquid and on filter paper for RVFV, Influenza, and HIV.

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Drs. Kehn-Hall and Jacobs (Co-PI, MRIGlobal) have received a three year grant from DTRA

Dr. Kylene Kehn-Hall and Dr. Jonathan Jacobs (Co-PI, MRIGlobal) have received a three year grant from DTRA entitled “Interactions of Alphaviruses with the Host MicroRNA Processing Machinery”. This project also involves a collaboration with Dr. Jonathan Dinman’s laboratory at University of Maryland. The objective of this grant is to determine the importance and mechanism of specific miRNAs in alphavirus replication, thereby understanding their potential as a host based therapeutic target.

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Dr. van Hoek receives COS 2012 Teaching Award

Awarding Authority: George Mason University College of Science

The Teaching Award recognizes COS faculty members at George Mason University who are outstanding teachers or mentors or who have made major contributions to COS educational activities during the 2010–2011 academic year.

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Certificate of Registration

The George Mason University Biomedical Research Laboratory received the Certificate of Registration from the Centers for Disease Control prevention on February 27, 2012. This certification approves the Biomedical Research Laboratory to work with Centers for Disease Control (CDC) and Animal and Plant Health Inspection Service (APHIS) select agents.

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JSTO – In the News (CBS Input – December 2012)

DTRA Funded Effort Studies Anti-infective Properties of Reptile Serum

Seven months ago, DTRA initiated a research effort to take advantage of the anti-infective properties of reptile serum. The concept is to identify and use constitutive parts of serum that enables animals to fight infection, notably cationic antimicrobial peptides. These peptides will be isolated using a novel, nanoparticle-based approach.

The foundation for this DTRA-funded work is research performed at George Mason University (GMU) in the laboratories of Dr. Monique van Hoek (National Center for Biodefense and Infectious Diseases) and Dr. Barney Bishop (Department of Chemistry) that demonstrated anti-microbial and anti-biofilm properties of these CAMPs. Recently, their published work has been recognized by the respective journals as being among the highest viewed articles.  For example, their paper in Frontiers in Microbiology has received 1391 views [1]. The companion paper in BMC Microbiology was “Highly Accessed” with 5647 views so far [2], and a second companion paper in BBRC received a favorable score in a Faculty of 1000 review [3,4]. All of the researchers and students involved are very excited to be working on this project. The principal investigator on the project HDTRA1-12-C-0039 “Translational Peptides for Personal Protection” is Dr. Joel Schnur. (POC Al Graziano, 767-3360)

1. Dean, S. N., Bishop, B. M., & Van Hoek, M. L. (2011). Susceptibility of Pseudomonas aeruginosa biofilm to alpha-helical peptides: D-enantiomer of LL-37. Frontiers in Microbiology, 2.

2. Dean, S. N., Bishop, B. M., & van Hoek, M. L. (2011). Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus. BMC Microbiology, 11(1), 114.

3. Amer, L. S., Bishop, B. M., & van Hoek, M. L. (2010). Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella. Biochemical and Biophysical Research Communications, 396(2), 246-251.

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Dr. van Hoek receives 2009 J. Shelton Horsley Research Award

Awarding Authority: Virginia Academy of Science

The J. Shelton Horsley Research Award is the highest honor bestowed by the Virginia Academy of Science for original research. The presentation of a certificate and a monetary award are a highlight of the Annual Meeting.

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