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Mason Science Series: Treating the Next Pandemic Using Your Own Immune System

Dr. Hakami is the featured guest for the next Mason Science Series event hosted by the College of Science Dean Fernando Miralles-Wilhelm. Dr. Hakami will discuss his novel research into the regulation of immunity by extracellular vesicles (EVs) and also the development and characterization of a novel nanoparticle-based therapeutic platform called NESTED for treating infectious diseases. For more details, please go to the following link:

https://science.gmu.edu/UpcomingMSS

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Dr. Ramin M. Hakami has received an $80,000 grant from the Henry Klopp Trust

Dr. Ramin M. Hakami has received an $80,000 grant from the Henry Klopp Trust for studies of how a novel nanoparticle-based platform called NESTED provides protection against infectious diseases

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The van Hoek lab gives two talks at the upcoming Spring 2024 meeting of the Washington, D.C Branch of the American Society for Microbiology (ASM)

The van Hoek lab gives two talks at the upcoming Spring 2024 meeting of the Washington, D.C. Branch of the American Society for Microbiology (ASM). https://www.washingtondcasm.org/

Doctoral students Ashley Carpenter and Lulu Alsalih’s joint abstract has been selected for a Lightning Talk. 

Post-doc Sarah Alobaid’s abstract has been selected for an early career talk.  

The Meeting is April 12th at Howard University.

https://www.washingtondcasm.org/2024springmeeting 

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George Mason COS #Faculty Friday – Yuntao Wu

This #FacultyFriday features Yuntao Wu, Professor,

He has been studying viruses for over 30 years, and for the past 20 years, he has been primarily focused on studying HIV infection. Read below to learn about his research, and visit:

https://science.gmu.edu/directory/yuntao-wu

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Mason scientists explore innovative approach to silence HIV in the central nervous system, encourage scientific collaboration

Research team receives $2.95M in NIH funding to study cell-derived extracellular vesicle mediated epigenetic HIV silencing in the brain.

Read the full Article Here

Dr. Kashanchi

A collaboration including researchers from the Center for Infectious Disease Research at George Mason University is developing and characterizing a highly innovative modular approach that will utilize extracellular vesicles to deliver anti-HIV genes to virus-infected cells in the brain in an effort to epigenetically silence HIV expression in a long-term and stable manner.

Fatah Kashanchi, professor of Virology and Director of the Mason Science Laboratory of Molecular Virology, is the primary investigator on the National Institutes of Health funded collaboration which also includes Mason researchers, Yuriy Kim, Anastasia Marie Williams, and Heather Branscome; Lenny Schultz, a professor from The Jackson Laboratory; and Mason Science affiliate faculty, Kevin Morris, professor and director at The Griffith University Cell and Gene Therapy Group, Menzies Health Institute School of Pharmacology and Medical Sciences, in Queensland, Australia.

The methodology incorporates extracellular exosome delivery. Kashanchi said the effort could be likened to a package delivery. “The team is creating packages that are sent directly to a specific address within the central nervous system, perhaps to the brain ‘zip code’ or to the lymph nodes.” This package will change the actual structure of that viral  genome in the way it twists and turns so it can no longer be active. “For example, think of a normal double helix, then change the structure so that DNA is no longer usable, effectively silencing it with no side effects,” Kashanchi said. This silencing period would be in effect for the individual’s lifetime.

This method may also lead to a therapeutically relevant means to not only control HIV/HAND, (HAND is an HIV associated neurocognitive disorder that impacts memory and thinking), but could usher in a new highly innovative methodology that controls the epigenetic state of those genes involved in various other human diseases.

Kashanchi received $631,369 of the anticipated $2.95M from the National Institutes of Health for this research. Funding began in August 2023 and will end in late May 2028.

This and other breakthrough research efforts will be discussed in more detail during the upcoming annual meeting of the American Society of Intercellular Communication, (ASICbio.org), scheduled to occur from October 12 to 15, 2023.

Read the full Article Here

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Dr. Wu published a recent invited review article about HIV preintegration transcription and host antagonism.

Dr. Wu published a recent invited review article about HIV preintegration transcription and host antagonism.

The article gives the most comprehensive review of the subject in the past 20 years. https://pubmed.ncbi.nlm.nih.gov/37345240/

Dr. Yuntao Wu is a leading expert on HIV preintegration transcription. He discovered the synthesis of a functional Nef protein prior to HIV integration (Wu and Marsh, 2001, Science, 293:1503). 

This image below summarizes the main points covered in this review.

Retrovirus integration is an obligatory step for the viral life cycle. However, large amounts of unintegrated DNA (uDNA) accumulate during HIV infection. HIV preintergration transcription has been found to occur at low levels from a large population of uDNA even in the presence of host epigenetic silencing mechanisms. This review article summarizes previous studies, and discusses critical questions that await to be answered in the future.
The author Yuntao Wu, is a leading expert in the field of HIV preintergration transcription, and has published extensively in the area.
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The van Hoek lab has just published a paper describing the computational design of new antimicrobial peptides (AMPs) with activity against multi-drug resistant (MDR) Acinetobacter baumannii

This picture shows a field-emission scanning electron microscopy image of MDR A. baumannii AB5075 cells treated with HRZN-15 peptide.
Blebs can be seen on the bacterial membrane.

Fahad Alsaab, a current PhD student in Biosciences (MID concentration) and Shravani Bobde (a graduate of the same program) worked together to design and test a set of new peptides called HRZN, as in “horizon”, designed to be effective against MDR A. baumannii. The most active peptide killed these wound-infecting bacteria with a MIC of 4 ug/ml.

Additional authors include Scott N. Dean, another former member of the van Hoek Lab and graduate of the PhD Biosciences program at GMU and Gabriel Ascoli, a summer ASSIP student who worked with Fahad.

The paper was published in the journal Antibiotics (IF 4.8). 

https://www.mdpi.com/2079-6382/12/9/1396 

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Cosmos grant to support Biosciences student seeking treatment of drug-resistant bacteria

May 25th, 2023

The increase in bacteria capable of resisting some of the strongest medications available poses a serious threat to the health of all people. It is critical that researchers identify new ways to treat these infections and Biosciences PhD student, Alena James, is up to the task. She recently received a $5,000 Cosmos Scholar Grant to support research focused on different ways to treat one of these bacteria.

James’ research is an extension of a larger study funded by the Peer Reviewed Medical Research Program and led by Monique van Hoek, Professor of microbiology and infectious diseases in Mason’s School of Systems Biology. Van Hoek’s study focuses on Toxin-Antitoxin systems in bacteria and seeks to disrupt the ability of the “antitoxin” gene to regulate the “toxin” gene—ultimately killing the bacteria. If this approach proves successful, this would be a large step towards new treatments for bacteria that are otherwise resistant to available medications.

James will use the funding received through the Cosmos Grant to apply this approach to the biothreat bacterium Francisella. According to van Hoek,“the ability to specifically target expression of the toxin gene and cause bacterial cell death is a promising strategy in the fight against multidrug-resistant and dangerous bacteria.”

James earned a BA in Political Science and BS in Biology from Winthrop University, followed quickly with a Master’s in biology. James said she always held an interest in microbiology. As one of four children, she saw firsthand how financially difficult doctor and hospital visits could be on her parents. James said she wanted to be armed with enough medical knowledge to either treat herself and family directly, or allow her to make more informed decisions during health care visits.  

“My knowledge is power and the more I know about infectious diseases and about human anatomy I feel like I’m empowered to try and make small changes to protect myself and those I love against small microorganisms,” said James.

James started her career as an adjunct professor, teaching microbiology at York Technical College, and then continued her education with an MS in Biodefense from Mason’s Schar School of Policy and Government. Her MS led to several internships and contract supporting assignments with the government, including the State Department. Upon receiving an ORISE STEM Fellowship (Oak Ridge Institute for Science and Education), James handled biodefense projects, including risk management and risk analysis, for the U.S. Department of Homeland Security’s Science and Technology Directorate

While continuing full-time contract work, James said she wanted to further her education once more in microbiology—leading to her acceptance in Mason Science’s PhD in Biosciences. 

“Everyone in the program is supportive and we really push each other and learn from one another” James said. “Dr. van Hoek has created a really safe space for everyone.”

James said she was thrilled to see she was assigned van Hoek as a mentor after receiving her acceptance letter to the program. “I was familiar with her work and reached out to her immediately to start working in her lab.” 

James said she felt honored to receive Cosmos funding to support her research, as it recognizes the hard work she continues to put forth while balancing her full-time job. She hopes her work will support current scientific research and open the door to broader applications.

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Sanskruthi Sreepangi, and Mentor Dr. Ramin Hakami, win first place in Life Sciences at the 2023 College of Science Undergraduate Research Colloquium

May 11th, 2023

Congratulations to Dr. Hakami, and his student Sanskruthi Sreepangi for winning first place in Life Sciences at the 2023 College of Science Undergraduate Research Colloquium.

Life Sciences (Biology, Neuroscience, Forensic Science)

1st PlaceSanskruthi Sreepangi, Mentor: Ramin Hakami, Purification and Characterization of RIG-I Inducing RNA Species within Small Extracellular Vesicles Released from Cells Infected with Rift Valley Fever Virus  (Poster #12)

For more information go to https://science.gmu.edu/news/college-science-undergraduate-research-colloquium-recognizes-2023-winners

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Mason scientist to identify natural mechanisms of boosting immunity to fight infectious diseases

George Mason University Associate Professor of Infectious Diseases and Microbiology, Ramin M. Hakami recently received $265,000 to research natural mechanisms of boosting the immune response.

The natural immunity effort will build on prior funded research on use of processed COVID-19 patient samples to explore natural mechanisms that are available to fight and protect against COVID-19 infection.

The Hakami Lab, within Mason’s School of Systems Biology, has deep experience and demonstrated expertise in this research, previously contributing to development of the Respiratory Detox Shot to inhibit SARS-CoV-2 and the Influenza A virus in vitro, as well as extensive work on the role of extracellular vesicles during infection with SARS-CoV-2 virus. In addition to Hakami, the research project team will include Farhang Alem, Assistant Director of Scientific Operations within Mason’s Center for Infectious Disease Research (CIDR) and Interim Director of Mason’s Level-3 Biomedical Research Laboratory (BRL) as well as laboratory technicians, and Mason students from Hakami’s research group trained in the various components of the project research requirements.

“Our work will build on findings from the funding group’s prior in vitro studies, initial animal experiments, plus overseas clinical trials,” said Hakami. “So far, their results from these human clinical trials suggest that processed COVID-19 patient samples have the ability to boost the immune system to help protect against COVID-19 infection,” Hakami explained.

Over a two-year period, the team will focus on two areas: first identifying the mechanism by which this material actually boosts the immune system to fight off infection. The other aspect, which is much more challenging to decipher, is to find out the components within this material that is giving the immune system boost.

Another aspect of the research also piques Hakami’s scientific curiosity, since his lab seeks to understand how extracellular vesicles that are released from cells regulate immune response to infection. “We will also be looking to see whether the processed patient samples carry extracellular vesicle components that may also be, at least in part, contributing to this immune activation,” Hakami said.

“Mason Science researchers often form multidisciplinary teams to collaborate on different phases of complex, challenging research like this,” said Mason College of Science Dean, Fernando Miralles-Wilhelm.

In addition to Mason’s BRL and CIDR, collaborators from Mason’s Center for Applied Proteomics and Molecular Medicine will use mass spectrometry and RPPA to profile and analyze the proteins within the samples.

“Projects like this leverage many components across our research facilities, allowing Mason and our partners’ researchers from various scientific domains to offer novel points of view to uncover new discoveries,” Miralles-Wilhelm explained.