Center for Applied Proteomics and Molecular Medicine

Mason postdoc leads scientific breakthrough that could revolutionize cancer treatment

It isn’t often that someone graduates with a PhD and a scientific discovery, but George Mason University researcher Marissa Howard was no ordinary student.

Marissa Howard

Howard, BS Bioengineering ’17, PhD Biosciences ’22, leads a team of scientists who have discovered a way to “eavesdrop” on cellular communications that could revolutionize treatments for cancer and other maladies.

All cells are constantly communicating with other cells using what Howard calls “an internet of molecular information.” Researchers at Mason’s Center for Applied Proteomics and Molecular Medicine (CAPMM), where Howard has worked since she was an undergraduate, are the first scientists to successfully tap into this communications system, which tumors use to trick or block the immune system and attract normal cells.

Howard was recently awarded a $200k grant from the National Cancer Institute to further this work. It is a medical breakthrough that could drastically change the way cancer is treated.

“It’s fun to be able to get to the source of tumors and actually figure out what’s going on there,” said Howard, who completed some of this work as part of her dissertation. “That’s what all cancer researchers want to do—figure out what the tumor is ‘thinking’ so we can get better outcomes for patients.”

Howard and the team have been focused on a component of the cellular communication system called extracellular vesicles (EVs), which are packages of concentrated information housed within tiny membrane-enclosed bubbles. The EVs are shed from the surface of cells and can travel long distances to be received by distant cells, causing a change in the behavior of the message recipient.

In the past, EVs were studied in cultured cells or were captured from a patient’s blood, but the Mason team created a way to study the cancer EVs within a solid living tumor at their source by sampling the interstitial fluid (IF), the wet environment that bathes all cells within tissues. This is the first portrait of the tumor EV communication system at its origin. Their findings, with Howard as first author, were published in the Journal of Extracellular Vesicles.

Their research also showed a dramatic difference in the communication function of the different major types of tumor tissue EVs. The scientists isolated the two major types of tumor EVs and then used nanoparticles, a Nanotrap technology created by CAPMM researchers, to deliver them to a draining lymph node.

Howard said that the treatment of the lymph node with the two separate classes of EVs was associated with dramatic differences in the growth of distance metastasis in the lung. “Repeated tests done in mice proved one class of isolated mitochondrial EVs capable of preventing the metastasizing of cancerous breast tumors while another class promoted cancerous growth.”

The discovery means doctors could more quickly gauge the effectiveness of existing cancer treatments and make real-time adjustments based on the information derived from the cellular communications.

Marissa Howard with CAPMM Director Lance Liotta and College of Science Dean Fernando Miralles at Mason Innovation Awards. Photo by John Boal Photography

It’s for that reason that the team’s discoveries have further implications beyond cancer, according to Lance Liotta, a Distinguished University Professor at Mason and the cofounder and codirector of CAPMM.

“These specific markers for mitochondrial health allow EVs to be a novel biomarker/diagnostic tool for cancer and other mitochondrial disorder diseases, such as Parkinson’s disease, Alzheimer’s, Lou Gehrig’s disease, or muscular dystrophy,” Liotta said.

Howard first began working with Liotta and other CAPMM scientists as a bioengineering major participating in Mason’s Aspiring Scientists Summer Internship Program, where she spent the summer studying the electrical properties of their Nanotrap technology.

“I really loved it,” she said of the work. “[The CAPMM scientists] were excited by the work I was doing and asked me to continue working with them. I’ve been in the CAPMM lab since 2016.”

Howard is also an inventor and shares several patents with her CAPMM colleagues. For her senior capstone project, Howard led a team of bioengineering students to create a noninvasive urine-based tuberculosis (TB) test using CAPMM’s Nanotrap technology, and the invention, called TB Assured, garnered a lot of attention for the team and many awards, including a $15,000 prize from the National Institute of Biomedical Imaging and Bioengineering’s Design by Biomedical Undergraduate Teams (DEBUT) challenge to help develop the test further.

Everything that’s in the urine is captured by the Nanotraps, and you don’t need a centrifuge or other equipment,” said Howard, who completed her bachelor’s degree in bioengineering in 2017. “People loved it. They keep asking when it is going to be available at their local pharmacy.”

“I love the research space and the creative potential that comes with it,” Howard said. “You never know when your next idea is going to pop up.”

In addition to Howard and CAPMM’s Liotta, the EV research collaboration also included Alessandra Luchini, Amanda Haymond, and Fatah Kashanchi within the College of Science; collaborator Robyn Araujo at Queensland University in Australia; graduate students James Erickson, Zachary Cuba, Weidong Zhou, Purva Gade, Rachel Carter, Kelsey Mitchell, Heather Branscome, Fatimah Alanazi, Yuriy Kim; and high school students Shawn Kim and Daivik Siddhi.

Colleen Kearney Rich contributed to this article.

Mason scientists in I-SPY 2 trial discover first ever signatures of global resistance and response to prioritize breast cancer treatment selections, including in triple negative cases

The proprietary LCM-RPPA protein activation mapping technique of breast tumors identifies three biomarkers associated with global resistance and response, several new drug targets and predictive signature that may help prioritize future treatment selection.

A team of George Mason University molecular biologists at its Center for Applied Proteomics and Molecular Medicine (CAPMM) has identified novel proteomic based signatures of global resistance for certain breast cancer patients and specific therapeutic strategies needed to overcome resistance. The work recently described in Cell Reports Medicine identifies new drug targets activated in human breast cancer, and described a new HER2-EGFR protein activation/phosphorylation signature called HARPS that could provide for better outcomes for patients with triple-negative breast (TNBC) cancer disease that previously had no specific precision therapy strategy identified.

Mason scientists Rosa Isela GallagherJulia Wulfkuhle, and Emanuel Petricoin, used their laser capture microdissection (LCM) and reverse phase protein array (RPPA) technology to map the protein drug target activation architecture of more than 700 breast tumors from the I-SPY 2 TRIAL, collaborating closely with genomics and bioinformatic scientists within the Departments of Laboratory Medicine and Surgery at University of California, San Francisco, and members of the I-SPY 2 TRIAL. This correlative study involved women with high-risk stage II and III early breast cancer who were enrolled in the first eight experimental arms of I-SPY 2 plus concurrent controls.

Photo by: Ron Aira/Creative Services/George Mason University

“This effort, the largest proteomic analysis of clinical tumor epithelium samples of any cancer type ever, is a culmination of a decade of work, in collaboration with dozens of clinicians and researchers in the I-SPY 2 TRIAL,” shared Emanuel Petricoin, co-director of Mason’s Center for Applied Proteomics and Molecular Medicine. “The team used the LCM-RPPA platform to map the protein drug target activation landscape of breast tumors prior to the patients receiving any therapy and then identified specific proteins  that predicted response and resistance. No other precision oncology trial in the world is doing this,” said Petricoin, a Distinguished University Professor in the Mason Science School of Systems Biology.

The I-SPY 2 TRIAL, among the most widely known personalized medicine trials in the world today, pioneered the use of adaptive design strategies for rapid identification of targeted therapies that could benefit women with Stage II-III breast cancer.  Over 2,750 women at 40 clinical sites around the US have enrolled in I-SPY 2 since its inception. 

Researchers identified three specific proteins activated and expressed in human breast cancer that did not respond to any treatment. “The identified biomarkers associated with global resistance are cyclin D1, estrogen receptor alpha, and phosphorylated androgen receptor,” Mason Science Senior Research Scientist, Isela Gallagher said. “Because we found that global resistance to all drugs tested in the study was based on these 3 proteins being elevated and/or activated, we can target or turn off these proteins directly which will help the I-SPY2 TRIAL clinicians and their pharmaceutical partners prioritize new therapeutic strategies that target these proteins,” said Gallagher.

The team found that 11 specific protein activation-based signatures defined the breast cancers evaluated in the study, and identified specific precision therapeutics that would be optimized for best response. The CAPMM team also identified a novel signature called HARPS that can be used to stratify TNBC, the hardest to treat breast cancer subtype into HARPS+ who would best respond to anti-HER2 therapies or HARPS- who are predicted to best respond to immunotherapy. “The use of HARPS in TNBC could result in ~80% response rate compared to the current 30-40% response rate,” explained Mason Science Research Professor, Julia Wulfkuhle.  “We hope that ongoing and planned rigorous clinical validation of HARPS as well as the numerous predictive and prognostic signatures we describe in our paper will allow the eventual use of these candidate biomarkers in the clinical management of breast cancer patients”, Wulfkuhle said.

“The CAPMM team at George Mason University has served as essentially the I-SPY protein biomarker engine since its inception,” shared Laura Esserman, I-SPY 2 TRIAL primary investigator and Professor of Surgery and Radiology at UCSF.  “This novel approach gives our trials a powerful multi-omic molecular angle that is really unique in the precision oncology ecosystem,” explained Esserman, the Director of the UCSF Carol Franc Buck Breast Care Center.

“More importantly, the results give us clear targets that we can use to identify promising agents and test them in the I SPY 2.2 TRIAL- now that is bench to bedside translational research!” Esserman enthused. 

“We are extremely inspired by the work being done by the team at George Mason University and are proud to be able to commercialize these efforts,” shared Faith Zaslavsky, President and CEO of CAPMM partner, Theralink Technologies. “Breakthroughs like this will save lives and dramatically reduce the cost of unnecessary and ineffective treatments.”

This research effort was supported by funding from many partners including the Quantum Leap Healthcare Collaborative, various National Institute of Health grants, the Gateway for Cancer research grants, The Atwater Trust and the SideOut Foundation. Further information and requests for resources or data should be directed to and will be fulfilled by Rosa I. Gallagher (rgallag3@gmu.edu).

Innovation Awards celebrate Mason researchers

On May 9, George Mason University celebrated its research enterprise with Innovation Awards, recognizing the Innovator of the Year and a Mason start-up, and those who received and/or licensed a patent.

Michael Buschmann’s team accepted the Innovator of the Year award from Vice President Andre Marshall (holding plaque) on his behalf. Photo by John Boal Photography

According to David Grossman, senior director of technology transfer and industry collaboration in Mason’s Office of Research, Innovation, and Economic Impact, this was the first time since 2010 that the university formally recognized researchers. Going forward it will be an annual event.

“At the Mason Innovation Awards, we were privileged to recognize the tireless pursuit of knowledge and the transformative impact of our faculty’s discoveries,” said Grossman. “Through their dedication, these researchers are helping shape the world with their groundbreaking technologies and pushing the boundaries of what is possible.”

The Innovator of the Year Award was awarded posthumously to Michael Buschmann, Eminent Scholar and the former chair of the Bioengineering Department within Mason’s College of Engineering and Computing. Buschmann help found the start-up AexeRNA Therapeutics Inc., in partnership with the university’s Office of Technology Transfer. He and his team licensed the commercial rights of four patents to the company. The technology AexeRNA is working on will make mRNA vaccines less costly and more readily available worldwide. Members of Buschmann’s AexeRNA team were recognized at the ceremony.

Saleet Jafri was awarded the Mason Start-up Award. Photo by John Boal Photography

The Mason Start-up Award was presented to Saleet Jafri, director of Mason’s Interdisciplinary Program in Neuroscience and professor in the School of Systems Biology, College of Science, for his company Pathodynamics. Pathodynamics has licensed three Mason patents and is developing a technology that solves the problem of cancer drug resistance, which is responsible for more than 90% of cancer deaths. Jafri has also received a Small Business Innovation Research award for the technology and is working with the Virginia Small Business Development Center’s Innovation Commercialization Assistance Program (ICAP).

Lance Liotta (left) and David Grossman holding Liotta’s Lifetime Disclosure Award. Photo by John Boal Photography

University Professor Lance Liotta, cofounder and codirector of the Center for Applied Proteomics and Molecular Medicine, was recognized with a Mason Lifetime Disclosure Award. During his career, Liotta has filed more than 120 patent disclosures. Disclosures are the first step toward a patent by making a public claim about an invention or discovery. Liotta has 100 inventions to date and the prototype of one of these inventions—Laser Capture Microdissection, a method to procure subpopulations of tissue cells under direct microscopic visualization—is in the Smithsonian Institution’s collection.

During the program, Gisele Stolz, senior director of Entrepreneurship and Innovation Programs at Mason, was recognized for recently receiving an Impact Award from the Commonwealth Cyber Initiative for mentoring students. Stolz has helped place more than 150 Mason students in internships with cyber-related start-ups.

Participants of the Virginia SBDC ICAP and national I-CORPS programs and Mason researchers who have patented or licensed a technology or invention were also recognized.

The awards for patents and licensed technologies are Plexiglas hexagons with magnets so researchers can add to their award over the years as they receive patents/licensing.

A list of those Mason researcher licensing technologies follows.

Mason Licensed Technology Awards

“Microscopic Particles for Target Bio-markers,” licensed to Ceres NanoSciences
Lance Liotta, Emanuel Petricoin, Alessandra Luchini Kunkel, Barney Bishop, Virginia Espina, Marissa Howard, and Fatah Kashanchi

“Self-Cleaning Intrusion Tolerance” licensed to SCIT Labs
Arun Sood

“Pre-Shot Sniper Detection” licensed to First Guard Technologies
Kenneth J. Hintz

“Cauldron” licensed to Cyvision Technologies
Sushil Jajodia

“Antiretroviral Compositions” licensed to Lentx
Yuntao Wu

“Biological Materials” licensed to Kera FAST
Barney Bishop, Monique van Hoek, Robin Couch, and Yuntao Wu

“Atomic Magnetometer” licensed to Twinleaf
Karen Sauer

“Protein–Protein Interactions” licensed to EMD Millipore
Alessandra Luchini Kunkel, Lance Liotta, and Virginia Espina

“Antiretroviral Cyclonucleotides” and “Pseudovirus Platform” licensed to Virongy
Yuntao Wu and Brian Hetrick

“Packet Flow Watermarking” licensed to CyberRock Tech
Xinyuan Wang                     

“Encryption IP Cores” licensed to Chaologix
Gaj Krzysztof and Panasayya Yalla

“Personalized Therapy” licensed to Avant Diagnostics
Emanuel Petricoin and Julia Wulfkuhle

“Thromboembolism Sleeve” licensed to Phase II Consulting and Staffing
Lance Liotta and Marissa Howard

“Laser Capture Microdissection” and “Tissue Molecular Profiling” licensed to Targeted Biosciences
Lance Liotta, Alessandra Luchini Kunkel, Virginia Espina, Amanda Nicole Haymond Still, Marissa Howard, and Philip Andrew Pappalardo

“Cancer and HIV Therapeutics” licensed to Targeted Pharmaceuticals
Catherine DeMarino, Fatah Kashanchi, Lance Liotta, and Virginia Espina

“HIV Vaccine” licensed to Viropeutics
Yuntao Wu

“Protein Painting” licensed to Monet Pharmaceuticals
Alessandra Luchini Kunkel, Amanda Nicole Haymond Still, Lance Liotta, Mikell Paige, and Virginia Espina

“Antidepressant Selection” licensed to Teahorse
Farrokh Alemi

“Honeybee Hive Therapy” licensed to Tri-State Proteomics
Alessandra Luchini Kunkel, Lance Liotta, and Rocio Solange Prisby

“mRNA Delivery Lipids” licensed to AexeRNA Therapeutics
Michael Buschmann, Mikell Paige, Suman Alishetty, and Manuel Carrasco

“COVID Contact Tracing” licensed to Vericord
Farrokh Alemi and Janusz Wojtusiak

“Wearable Devices for Managing Substance Abuse” licensed to LifeSpan Digital Health
Holly C. Matto and Padmanabhan Seshaiyer

“Precision Oncology” licensed to Pathodynamics
Mohsin Saleet Jafri and Soukaina Amniouel

Mason Honey Bee Initiative

The George Mason University Honey Bee Initiative (HBI) is an interdisciplinary effort supported by the work and expertise of colleagues across the university (College of Science, College of Education and Human Development, College of Computing and Engineering, College of Visual and Performing Arts, School of Public Health, and the School of Business).

The initiative offers opportunities to engage in sustainable beekeeping, perform scientific research, design art projects, connect with the community, and even study abroad.

Partnerships with the government, for-profit businesses, non-profit organizations, and community members are vital to the success of the initiative.

Mason’s surveillance testing team honored for its efforts

Mason’s surveillance testing team honored for its efforts
John Hollis
Mon, 02/28/2022 – 15:46

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Mason formally recognized the many dedicated scientists, first responders, program administrators and medical personnel whose tireless efforts paved the way for the school’s successful COVID-19 surveillance testing program during the global pandemic. Photo by Evan Cantwell/Creative Services

George Mason University officials on Monday formally recognized the many dedicated scientists, first responders, program administrators, staff and medical personnel whose tireless efforts paved the way for the school’s successful COVID-19 surveillance testing program during the global pandemic.

The reception in their honor at Merten Hall was Mason’s way of giving a heartfelt thanks for a job well done.

“I can give you all a thousand thank you’s,” said Mason President Gregory Washington. “And I know the reality is that it doesn’t happen if you all don’t make the commitment, if you all don’t put in the hard work, if you all don’t put in the extra hours, if you all don’t have to deal with the changing policies and the struggles that we were in many cases foisting upon you. But you did it, you did it admirably and your results are spectacular.”

Since the program’s inception in fall 2020, Mason has administered more than 155,000 COVID tests to students, faculty and staff. Processing the tests in Mason’s own labs means results are returned within 24 to 48 hours. The fast turnaround time meant Mason scientists could quickly identify and isolate positive COVID cases which lead to timely notification to those members of our community that needed to self-isolate to mitigate outbreaks within the Mason community.

The quick turnaround required immense time and staff power, key factors in helping keep the community safe while elevating Mason to national prominence for its response to the pandemic. The university’s ability to  monitor the prevalence of COVID within the campus community and transmission rates played a key role in the decision to open its doors on time for fall 2021 and spring 2022 semesters.

Lance Liotta, the co-founder and co-director of the Center for Applied Proteomics and Molecular Medicine within Mason’s College of Science which oversaw the testing, called what his team accomplished “historic.” Liotta noted that his team conducted 1,000 thousand tests on Friday, Feb. 25, without a single positive case of COVID.

Carol Kissal, Mason’s senior vice president for administration and finance, lauded the team for their efforts that have served to inspire the entire Mason community.

“You have all been part of something that is pretty phenomenal,” she said.

The surveillance and diagnostic testing program started in the Ángel Cabrera Global Center parking garage in late August 2020, where staff overcame the elements and other unexpected technological hurdles to help Mason navigate the early stages of the COVID pandemic and COVID virus of which very little was known at the time. It wasn’t long before Mason’s COVID Response Team and scientists had devised new collection procedures at sites across all of Mason’s campuses, each aimed at keeping site staff and test participants safe through an efficient and expeditious testing process.

Mason’s reliable surveillance testing system is also critical in allowing Mason student-athletes to continue competing safely throughout the pandemic.

 

Honey bees and their honey could be a big help in solving police cases

Honey bees and their honey could be a big help in solving police cases
John Hollis
Tue, 01/18/2022 – 14:33

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Volunteers plant perennials at the Forensic Science Research and Training Laboratory in support of ongoing research to determine if traces of human remains can be identified in the plants or in the honey produced by pollinators. Photo by Shelby Burgess/Strategic Communications

An unlikely collaboration between George Mason University’s Honey Bee Initiative and the new outdoor Forensic Science Research and Training Laboratory could yield critical advances in forensic science. 

Mason teams from a number of different fields are working in unison at the Science and Technology Campus in Manassas, Virginia, on an ambitious project to see if the honey produced by bees after feeding on flowers can help them better locate missing persons. 

“The focus of forensics is to solve cases,” said Mary Ellen O’Toole, the head of the Forensic Science Program within Mason’s College of Science and a former FBI profiler. “Outdoor crime scenes have always posed a challenge to investigators, particularly identifying the location of human remains. The bee research will allow us to scientifically demonstrate that identifying bee activity in bee farms or in the wild and analyzing their proteins can help lead investigators to human remains. In this case, the bees are our new partners in crime fighting, and that’s amazing science.” 

Proteins in bee honey contain biochemical information about what the bees have fed upon. That information has previously been used to detect the chemical signature of pesticides in honey, allowing observers to deduce what specific types of pesticides were being used within the five-mile radius from the hives that honey bees typically frequent. 

Similarly, O’Toole and her team believe that volatile organic compounds (VOCs) of human decomposition might likewise be found in bee honey, allowing authorities to then triangulate where missing human remains might be located. That ability could ultimately help spare grieving families additional extended angst while also saving thousands of hours in the search for a missing person. 

“If we can determine what the VOCs are for humans and differentiate that from other animals, we could then use the bees and their honey as sentinels, and, hopefully, find missing persons and solve cases,” said Anthony Falsetti, an associate professor of forensic science. 

Their belief is based on the premise that flowering plants near dead bodies will uptake the VOCs before being fed upon by the bees and ultimately being deposited in their honey. 

Alessandra Luchini, an associate professor within Mason’s Center for Applied Proteomics and Molecular Medicine (CAPMM), has perfected a method to extract proteins from the honey. She and Lance Liotta, a University Professor and CAPMM co-founder and co-director, have been involved with the project from the outset, following the idea’s origins at one of the monthly research meetings with the Forensic Science Program. 

Honey bees are very specific in the kinds of the flowers to which they’re attracted. Doni Nolan, Mason’s Greenhouse and Gardens sustainability program manager from the School of Integrative Studies within the College of Humanities and Social Sciences, applied her expertise to the project, choosing the right flowers to plant within the specific one-acre section of the newly opened Forensic Science Research and Training Laboratory that will house the remains of human donors in a heavily wooded area. The honey bee hive on the SciTech Campus is located several hundred yards away from the Forensic Science Research and Training Laboratory. 

Volunteers prepare to plant flowers at the Forensic Science Research and Training Laboratory. Photo by Shelby Burgess/Strategic Communications

In November, students and researchers planted several different species of plants, which bear highly scented white and yellow blossoms, near the spots where the human remains will soon be displayed. Additional plants native to this area will be planted in the spring before the first honey samples are examined, Nolan said. 

“You’re trying to see if the honey and the bees can help us find a body and solve a homicide,” said Nolan, who has a biology degree from Mason and is working on a PhD in biosciences. 

The five-acre, Forensic Science Research and Training Laboratory opened in early 2021, making Mason just the eighth location in the world capable of performing transformative outdoor research in forensic science using human donors and the only one in the Mid-Atlantic region. 

Donation of human remains to the research facility will come through the Virginia State Anatomical Program (VSAP), which is a part of the Virginia Department of Health. Go here to learn more about donating your body to science. 

Mason also entered a partnership with FARO Technologies, Inc. that resulted in the world’s first FARO-certified forensic laboratory. 

In addition to those in the Forensic Science Program, the multidisciplinary project also includes the caretakers of the honey bees, as well as researchers and students from CAPMM, as well as from the Department of Environmental Science and Policy within the College of Science and Office of Sustainability, all of whom helped select the plants for the research design.

Mason research could change the way concussions are diagnosed

Mason research could change the way concussions are diagnosed
Colleen Rich
Thu, 07/01/2021 – 10:54

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Two research professors at George Mason University, in collaboration with global partners, have discovered the same protein biomarkers in the saliva of youth and collegiate athletes who have experienced concussive and sub-concussive impacts.

Shane Caswell

The findings, if validated in larger, independent studies, could be used to develop a new, rapid, noninvasive, saliva-based test for concussion diagnosis and management, as well as a way to monitor changes to the brain following exposure to repetitive sub-concussive impacts.

The study, conducted by Mason professor of athletic training Shane Caswell and University Professor Emanuel Petricoin, was recently published in the Journal of Neurotrauma.

“Salivary biomarker research can, hopefully, enhance already existing tools that diagnose concussions, as well as track brain health over time,” said Caswell, one of the study’s lead researchers and executive director of Mason’s Sports Medicine Assessment, Research, and Testing (SMART) Laboratory. “This is valuable, not only in all levels of sports, but also in military settings.”

Concussion and repeated sub-concussive impacts, which are blows to the head that do not produce immediate symptoms, could have long-term adverse health consequences if athletes return to contact activity too soon.

Concussion management currently relies on subjective measures to inform clinical judgement. New strides have been made recently, such as a handheld blood test developed by Abbott Laboratories to diagnose concussions. But there continues to be limited understanding of how repeated sub-concussive impacts, that frequently do not cause concussion symptoms, affect the brain.

Emanuel Petricoin

“There is a need for nonsubjective, diagnostic measures to be able to assess someone’s traumatic brain injury level, either in a concussed or sub-concussed state,” said Petricoin, co-director of Mason’s Center for Applied Proteomics and Molecular Medicine (CAPMM). “This is important for health care providers so that they can make accurate medical judgements.”

Mason’s research identified antibodies in saliva that target proteins such as HTR1A, SRRM4, and FAS, which are known to play a role in brain physiology and function. Their presence correlates with concussions and how many hits and athlete sustained during a season of play.

Compared to healthy athletes, individuals who were diagnosed with a concussion, or who suffered high exposure to sub-concussive impacts, showed an elevation of the same salivary biomarkers.

The research team worked with youth, high school, and collegiate athletic teams and their medical staffs across the Washington, D.C., metropolitan area, to collect saliva to create a Sport-Related Head Trauma Salivary Biobank. This first-of-its-kind biobank contains saliva collected from healthy athletes, athletes diagnosed with concussions, and athletes who sustained repetitive sub-concussive impacts.

Sensors worn by the athletes measured the number and severity of hits. Collected saliva was tested using a Mason-developed nanoparticle technology. Analysis was completed by researchers at the KTH Royal Institute of Technology in Stockholm, Sweden, which is a leader in the world of autoimmunity research.

“Once someone has experienced a concussion, it is hard to know when they are fully healed from it, meaning it may take less of an impact for a second concussion to occur,” Petricoin said. “It’s important to study concussion biomarkers in youth because growing evidence suggests that if we can monitor head impacts more effectively, it will support their long-term health.”

Mason start-up Ceres Nanosciences experiences big wins and increases footprint in Prince William County

Mason start-up Ceres Nanosciences experiences big wins and increases footprint in Prince William County
Colleen Rich
Tue, 04/20/2021 – 08:49

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Ross Dunlap is CEO of Ceres Nanosciences and a member of the George Mason Research Foundation board. Photo provided

Ceres Nanosciences, a Northern Virginia bioscience company spun out of George Mason University that specializes in diagnostic products and workflows, has opened a 12,000-square-foot advanced particle manufacturing plant in Prince William County’s Innovation Park. The new facility increases the manufacturing capacity of Ceres’ Nanotrap® Magnetic Virus Particles, which improve diagnostic testing for viruses like SARS-CoV-2, influenza, and respiratory syncytial virus.

 

The completion of the new facility also reflects the partnership between Mason and the Prince William County Department of Economic Development (PWCDED).

 

“The PWCDED has a long-standing relationship with Mason, specifically with the Science and Technology Campus that anchors our bioscience hub in Innovation Park,” said Christina Winn, executive director of PWCDED. “Ceres was the first company to graduate our Science Accelerator, and we are invested in their growth as a leader, collaborator and innovator in our life sciences industry cluster.”

 

The construction of the facility, which was completed in under four months, was funded by the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics (RADx) initiative to expedite the production and commercialization of diagnostic tests for the SARS-CoV-2, the virus that has become known as COVID-19. Prince William County also supported the swift development of the site.

 

“We’re immensely grateful for the NIH funding that supported this new facility,” said Ross Dunlap, Ceres Nanosciences CEO. “Not only are we now able to deliver a robust supply of this critical reagent that the industry needs, but the facility also is a major element of Ceres’ long-term growth plan.”

 

Dunlap and his team have noticed significant gaps in the diagnostics industry and infrastructure in the United States, especially in response to an outbreak. He hopes that because the Nanotrap® Magnetic Virus Particles reduce sample processing time, eliminate the need for special kits, and create cost efficiencies, the technology can be leveraged to respond faster to future pandemics.

The Ceres Nanosciences production team. Photo provided

“It was very fortunate that we had put a lot of energy into developing the technology for viral infections and released a product for it before the pandemic, not even knowing that COVID-19 would come about,” said Dunlap, who serves on the George Mason Research Foundation board. “We were able to rapidly respond and quickly validate our technology for COVID diagnostics, which was done in partnership with Mason.”

 

The base technology underlying the Nanotrap® particle was created by Mason’s Center for Applied Proteomics and Molecular Medicine (CAPMM), which is led by co-directors Lance Liotta and Emanuel Petricoin. The technology was funded with a series of NIH grants from the NIH lnnovative Molecular Analysis Technologies (IMAT) program.

 

It was then licensed to Ceres Nanosciences in 2008. Follow-on funding to advance the technology was awarded to the Ceres and Mason team by the NIH, the Center for Innovative Technology, Virginia Catalyst, the Bill and Melinda Gates Foundation and the Department of Defense.

 

“We are very proud to see that a technology developed under NIH funding at Mason has graduated to a product that is aiding in the fight against COVID-19 and promises to help patients all around the world for many other diseases,” said Alessandra Luchini, associate professor for CAPMM and co-inventor of the Nanotrap®.

 

With the assistance of Mason researchers, who played a large role in efforts such as testing particles and generating data, the technology evolved into a platform that can be modified and adapted to different applications, such as infectious diseases. For example, in 2015, Mason CAPMM scientists and Ceres Nanosciences demonstrated the use of the Nanotrap® technology for the detection of Lyme disease. Today, the Lyme Borrelia Nanotrap® Antigen Test is offered by Galaxy Diagnostics, a medical laboratory that specializes in tests for flea- and tick-borne pathogens.

 

“Mason has a lot to offer when it comes to cutting-edge technologies,” said Hina Mehta, director of the Office of Technology Transfer. “We are always looking for the right partners, like Ceres Nanosciences, who can take our research discoveries to commercial-grade products that benefit the public.”

 

Ceres Nanosciences and Mason have worked together since the company’s genesis. Ceres’ first lab was on Mason’s Science and Technology Campus, and the two organizations have collaborated on numerous research projects.

 

“Mason has consistently been a resource that we go to when we need extra support and research power,” said Dunlap. “The researchers have a range of backgrounds that we need: from virology to microbiology to proteomics. Their areas of expertise have been critical across a lot of our development programs.”

 

Dunlap said he and his team, along with continued support from Mason, are eager to help people return to pre-pandemic life.

 

“Our team is incredibly excited and motivated to come to work every day and produce these particles so that people can go back to work and school,” said Dunlap. “We’re proving why this technology has such value and why it can do so much for public health.”

 

Doctoral student combines love of lab research with practical applications

Doctoral student combines love of lab research with practical applications
Colleen Rich
Mon, 03/29/2021 – 13:48

Body

Mason doctoral student Marissa Howard has worked at the Center for Applied Proteomics and Molecular Medicine (CAPMM) since 2016. Photo by Evan Cantwell/Creative Services

When Marissa Howard first came to George Mason University as an Honors College student and a scholar in the Louis Stokes Alliance for Minority Participation (LSAMP) Program, she was a biology major.

As she began looking for hands-on research experiences, her LSAMP mentor, Volgenau School of Engineering professor Alok Berry, suggested she give bioengineering a try.

“It really clicked for me,” said the Richmond, Virginia, native, and she ended up switching her major to bioengineering.

In her junior year, Howard participated in Mason’s Aspiring Scientists Summer Internship Program (ASSIP). That’s when she met Mason researchers Lance Liotta and Alessandra Luchini. She spent the summer studying the electrical properties of their Nanotrap technology.

“I really loved it,” she said. “I really loved them, and they were excited by the work I was doing and asked me to continue working with them. Since 2016, I’ve been in [the Center for Applied Proteomics and Molecular Medicine (CAPMM)] lab.”

Biosciences PhD student Marissa Howard tests vaccine efficacy in healthy and immunocomprised patients by running a rapid COVID-19 antibody test. Photo by Evan Cantwell/Creative Services

For her senior capstone project in 2016-17, Howard led a team of bioengineering students—Sara Sharif, Sameen Yusuf, and Rohit Madhu—to create a noninvasive urine-based tuberculosis (TB) test called TB Assured, and the invention garnered a lot of attention for the team and many awards.

In addition to winning several Mason awards for being the best project of the year, the team also won the $15,000 prize from the National Institute of Biomedical Imaging and Bioengineering’s Design by Biomedical Undergraduate Teams (DEBUT) challenge to help develop the test further.

TB Assured started as a dipstick test, much like pregnancy tests, that would find biomarkers of TB in urine. In an effort to make the test more sensitive and user friendly, Howard came up with the idea of using a paper origami cup as a next generation urine collection cup for the test instead of a test strip.

The biomarker-harvesting Nanotraps are in a glass wool-like substance embedded in the cup. After use, the cup is emptied, collapsed back into its original flat, two-dimensional form, and can be mailed in an envelope for processing.

Everything that’s in the urine is captured by the Nanotraps, and you don’t need a centrifuge or other equipment,” said Howard, who completed her bachelor’s degree in bioengineering in 2017. “People loved it. They keep asking when it is going to be available at their local pharmacy.”

Howard is now a doctoral student in biosciences at Mason. During the coronavirus pandemic, Howard was able to get back into the CAPMM lab, but now all the researchers are working on COVID-19-related research.

“We are doing some of the analytical validation studies to help different companies file for FDA approval for their rapid COVID-19 antigen tests,” Howard said. “That’s been really interesting and fun—seeing all these different tests that come in.”

For her dissertation, Howard is focusing on cancer research. She is looking at how cancer exosomes (small, membrane-wrapped packages released by cells) communicate. The findings could help create a new kind of immunotherapy.

“[Looking at the exosomes in a tumor sample] is going to tell you a little bit more information than just the pathology would,” she said. “It’s sort of telling you what that tumor is thinking and how it is communicating to its neighboring cells.”

With completing her PhD still about a year away, Howard is planning a future in a lab, possibly in an academic setting.

“I love the research space and the creative potential that comes with it,” Howard said. “You never know when your next idea is going to pop up.”

Mason COVID antibody testing shows a lot of promise in the body’s ability to fight the virus

Mason COVID antibody testing shows a lot of promise in the body’s ability to fight the virus
John Hollis
Mon, 03/01/2021 – 16:10

Body

COVID-19 antibody research by Lance Liotta and his team has shown the human immune system is better able to fight the virus than initially believed. Photo by Evan Cantwell/Creative Services

George Mason University researchers say their study of COVID-19 antibodies in people previously been infected with the virus reveals the human immune system’s strong ability to fight the virus, even if they showed minimal or no symptoms. Additional early results are showing that the vaccines being rolled out to combat the global pandemic generate a strong immune response. 

Lance Liotta, the co-director, co-founder and medical director of the Center for Applied Proteomics and Molecular Medicine (CAPMM) within Mason’s College of Science, and his colleagues are using an improved COVID-19 antibody test developed as part of a Mason clinical study to measure the body’s response to the vaccine. 

Based on months of study of patients who were naturally infected, Liotta and his team were able to verify that patients’ antibodies lasted longer than initially first believed and that they potentially helped prevent those patients from getting sick again. Early results of those who have been vaccinated have confirmed the shots to be strong boosters to the human immune system’s ability to combat the virus by generating more antibodies that block the virus spike protein tips. Tips of the spikes are the starting point for the virus to enter the patient’s cells. 

“This research offers truth and hope,” Liotta said. “The public is anxious and very worried about the virus. They want to know if the vaccines work. They want to know if the antibodies made by the body after a natural infection or after a vaccine will actively work to fight the virus. If I do get sick, can these antibodies help me? 

“The answer is yes.”  

That welcome revelation could be key in lessening the chance for severe sickness and limiting the spread of the virus. 

“Nevertheless we can’t let down our guard, and we must maintain social distancing and mask wearing practices that has protected our students and staff so well,” said Julie Zobel, Mason’s assistant vice president for Safety, Emergency and Enterprise Risk Management.  

Additionally, the expanded antibody research is providing scientists new clues about devising treatments for COVID-19, Liotta said, because of the many ways each of the different antibodies combat the virus. 

“We are humbled at how good the immune system is at fighting this,” Liotta said. 

Liotta and his team began their initial COVID-19 antibody study at the start of the global pandemic last spring. The testing allows scientists see how the body recognizes and reacts to the virus, particularly important when it comes to asymptomatic cases. 

“[Some of the subject tested] never knew that they had contracted COVID,” Liotta said, “but we can tell by looking at the antibodies that exist in their body. That’s a very important piece of information.” 

Antibodies, which are Y-shaped proteins generated by the immune system’s white blood cells, could prove critical in the fight against COVID-19. They attach to antigens much like a key to a lock to destroy invading germs. Once exposed to the virus, the body creates memory cells that will henceforth recognize the invader and spur the immune system to create antibodies to fight it in the future. So having antibodies to COVID-19 could possibly prevent people from becoming infected with the virus again. 

The aim of COVID-19 vaccinations is to stimulate a similar antibody response that would provide that protection from the virus. Liotta’s team of internationally recognized experts in diagnostic testing includes colleagues Virginia Espina, the research professor who oversees the Center for Applied Proteomics and Molecular Medicine’s CAP/CLIA certified laboratories, and Alessandra Luchini, the associate professor overseeing the development of the laboratory antibody assay in the nanotechnology lab. They will collectively use their expertise in clinical laboratory medicine, biochemistry, bioinformatics, molecular biology and infectious diseases to confirm those antibody responses. 

“Mason has been on the forefront of COVID research,” Espina said. “Since March, we have been working on different aspects of COVID research, and [Mason has been] very responsive to testing and keeping the campus community safe. We have done a wonderful job as a university in being able to keep the university open, prevent layoffs and allow students to come back onto campus.”