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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.

It isn’t surprising the George Mason University, a university that has been recognized for its innovation and entrepreneurship, would be among the top 100 universities in United States for patents. This fall, the National Academy of Inventors ranked Mason No. 91 in its list of the top 100 universities granted patents during 2022.

“Mason is in the business of discovery,” said Andre Marshall, vice president for research, innovation, and economic impact. “Our researchers are curiosity-driven. As such, we don’t always know where our research will lead or what impact it may have. I am absolutely delighted that the Mason Enterprise tech transfer team is working with our researchers on inventions and patents to transform our discoveries into impact.”

In 2022, the U.S. Patent and Trademark Office issued 15 utility patents to Mason inventors including a method to monitor physical cues for people in recovery, a wearable device for knee injuries, a system for detecting power grid states and determining appropriate actions, and therapeutics for dealing with human immunodeficiency virus (HIV), to name a few. Utility patents cover the creation of a new or improved—and useful—product, process, or machine.

Mason professors Padmanabhan Seshaiyer of the Department of Mathematical Sciences and Holly Matto, Department of Social Work, share a patent for systems and methods for biobehavioral-regulation treatments. Their invention provides recovery support for users by monitoring their biobehavioral state and strategically delivers, in real time, personalized recovery cues to treat and prevent relapse. It is the first patent for the Department of Social Work.

Researchers Marissa Howard and Lance Liotta at Mason’s Center for Applied Proteomics and Molecular Medicine patented a wearable device that measures, tracks, and monitors a wearer’s physical physiological conditions during a rehabilitation period. The device collects metrics, such as temperature, patellar shifting, limb circumference, and acceleration, and communicates them through a networked communication system so medical personnel and patients can stay updated with the patient’s rehabilitation progress and make adjustments.

Mason alum Eniye Tebekaemi, PhD Information Technology ’18, and Duminda Wijesekera of the College of Engineering and Computing were awarded a patent for a secure overlay communication model for decentralized autonomous power grids. The model is a logic-based system deployed onto computing devices in power grid stations and substations. In response to detecting various power grid faults, such as line failures and over-current states, the system can automatically rearrange power line configurations.

Researcher Yuntao Wu, a professor in Mason’s School of Systems Biology and the Center for Infectious Disease Research, was awarded two patents in 2022 for his work on HIV: “Targeting the Cofilin Pathway” and “Method and System for Inactivating Virus Infectivity for Producing Live-Attenuated Vaccines.” Wu has devoted his career to HIV research. In 2013, he founded the biotech company Virongy after licensing an HIV drug-screening technology that was developed in his Mason lab.

“The Office of Technology Transfer takes great pride in the quality of patented innovations brought forth by our dedicated researchers,” said David Grossman, senior director of  Technology Transfer and Industry Collaboration at Mason. “We are honored to help these innovators transition their groundbreaking concepts from the laboratory to the marketplace. This collaboration between academia and industry underscores our unwavering commitment to harness the full potential of research for the betterment of society.”

The academy’s Top 100 lists are created using data provided by the U.S. Patent and Trademark Office. Other Virginia universities in the top 100 included University of Virginia at 52 and Virginia Commonwealth University at 86.

According to the National Academy of Inventors press release, “This new list was created to highlight and celebrate American innovation and to showcase the universities that play a large role in advancing the innovation ecosystem within the U.S. and beyond.”

George Mason University’s Alessandra Luchini is among the 12 educators statewide set to be formally recognized by the State Council of Higher Education for Virginia (SCHEV) with a 2023 Outstanding Faculty Award.

Alessandra Luchini
Photo by Creative Services

Luchini, a professor in Mason’s Center for Applied Proteomics and Molecular Medicine (CAPMM) within the College of Science, is Mason’s 28th faculty member to be so honored since the award’s inception in 1987.

“This has been unbelievable,” said Luchini, the director of the Biosciences PhD Program within the School of Systems Biology, “because it is the highest honor in Virginia, and there are so many thousands of faculty with huge impact in their research. It is a complete honor, and I am incredulous.”

Outstanding Faculty Awards recognize faculty at Virginia’s public and private colleges and universities who exemplify the highest standards of teaching, scholarship and service. The award includes a $7,500 gift from the Dominion Energy Charitable Foundation when they are formally recognized at an in-person ceremony in Richmond on March 7.

Mark R. Ginsberg, Mason’s provost and executive vice president, lauded Luchini for her efforts.

“Professor Luchini is an exemplary member of the Mason faculty,” Ginsberg said. “I am delighted she has been recognized for her dedication to the education and development of her students and her outstanding and higher consequential research. She exemplifies the Mason spirit and is setting an example for future educators and scientists who will no doubt stand on her shoulders.”

Luchini’s research interests include developing technologies that improve current diagnostics and therapeutics for diseases, including cancer and inflammatory and infectious diseases.

She is a co-founder of Ceres Nanosciences Inc., which was created in 2008, and Monet Pharmaseuticals, created in 2019. In 2011, Luchini was named one of Popular Science’s Brilliant 10.

Most recently, Luchini contributed to the fight against Lyme disease by help leading a team of CAPMM researchers that was named one of 10 Phase 1 winners of the LymeX Diagnostic Prize by the U.S. Department of Health and Human Services and the Steven and Alexandra Cohen Foundation.

“Lyme disease is probably what I have been closer to,” Luchini said. “I interact with doctors who recommend patients for our clinical trials, I interact with patients and I hear their stories and, hopefully, my research allows them to understand a little bit more about what they have and how they can improve their health. It is a good reality check and a good reminder of why we do what we do—which is to help people.”

Outstanding Faculty Award nominees are selected by their institutions, reviewed by a panel of peers and chosen by a committee of leaders from the public and private sectors. SCHEV received 74 nominations this year before the group was narrowed to 24 finalists and the 12 eventual winners.

University Professor Lance Liotta is the co-founder and co-director of Mason’s Center for Applied Proteomics and Molecular Medicine. Photo by Creative Services

A George Mason University team led by Alessandra Luchini and Lance Liotta has been named one of 10 Phase 1 winners of the LymeX Diagnostics Prize by the U.S. Department of Health and Human Services (HHS) and the Steven and Alexandra Cohen Foundation.

Each of the Phase 1 winners have received $100,000 and an invitation to participate in the second phase of the contest whose aim—depending on future funding— is to accelerate the development of Lyme disease diagnostics.

“This is an important, direct test for tick pathogens that can be used not only for diagnostics, but also to monitor the success of treatment,” said Liotta, a University Professor and the co-director and co-founder of the Center for Applied Proteomics and Molecular Medicine (CAPMM) within Mason’s College of Science. Luchini is a professor within CAPMM.

Research by the Mason team centered around a urine-direct test that targets specific protein molecules made by the Lyme organism itself to provide direct information about pathogen activity and Achilles’s heel targets for acute and persistent Lyme disease, in many ways similar to long COVID.

The ultimate goal of the competition is to help expedite the development of diagnostics for Food and Drug Administration review.

Luchini said she was “honored and excited” about the selection of their work.

Alessandra Luchini is an associate professor within CAPMM. Photo by Creative Services

“This is a great opportunity to bring our research work to the next level, to transform the technology into a test that can be run in any clinical laboratory and help thousands of patients with their struggles with Lyme disease,” she said.

There were 52 entries in the contest’s first phase, using techniques such as radiological imaging, geonomics sequencing and microfluidics, according to the Cohen Foundation. Approaches used for diagnosing other infectious diseases, such as COVID, were incorporated into some of the submissions. Technical reviewers evaluated the submissions before they went to the panel of judges.

“Early detection and treatment are essential in the fight against this debilitating disease. The Phase 1 winning solutions provide hope for a future in which anyone can quickly and easily get an accurate Lyme disease diagnosis,” said Cohen Foundation President Alexandra Cohen. “We look forward to advancing the next generation of innovative Lyme disease diagnostics and providing the necessary structure for winners on their path to FDA review and approval.”

Lyme disease is the most common vector-borne disease in the United States. Caused by the bacterium Borrelia burgdorferi, it is most often transmitted to humans through the bite of infected blacklegged ticks. Typical symptoms include fever, headache and fatigue. If left untreated, the infection can spread to joints, the heart, and the nervous system.

The current two-tier serological testing system used to detect Lyme disease relies on the presence of antibodies and can only be used four to six weeks after infection to assess prior exposure. In contrast, the Mason test measures proteins coming directly from the bacteria, thus it provides a real-time reading on the state of the infection.

Emanuel “Chip” Petricoin is the co-founder and the co-director of Mason’s Center for Applied Proteomics and Molecular Medicine. Photo by Creative Services

A team of George Mason University scientists has a role in the White House Cancer Moonshot Initiative, and their work could help in the mission to reduce cancer rates in half over the next 25 years. 

The U.S. government is partnering with researchers to reduce  cancer deaths by bringing together a large community of patients, advocates, researchers and clinicians. 

Researchers from the Center for Applied Proteomics and Molecular Medicine (CAPMM) within Mason’s College of Science are working on a molecular profiling technology that would better identify the most effective drugs in the fight against specific cancers.  

“I think it’s very realistic to reduce cancer death rates in half in 25 years,” said Emanuel “Chip” Petricoin, a University Professor and the co-founder and co-director of CAPMM. 

Petricoin cited better technologies and approaches for early detection, a growing cadre of targeted therapeutics and immunooncology drugs that are precision-tuned for specific individuals, and the democratization and commoditization of molecular profiling that allows patients to get therapies tailored to their specific needs as the reasons for his optimism. 

The development of the Reverse Phase Protein Array (RPPA) as part of the Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) network is helping to prepare patients for therapy in future versions of the trials. 

His team’s unique approach and a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory are two big reasons why Mason’s CAPMM team has been continuously funded by the Department of Defense’s Apollo Moonshot project for the past four years, Petricoin said. 

The CAPMM team has a new initiative to develop a far less invasive “liquid biopsy” assay technology platform that requires a blood sample rather than a tumor biopsy to provide specific drug target information that will better fight the cancer. 

Petricoin likes the direction in which he sees the research headed and says the only potential obstacle would be convincing insurance companies and pharmaceutical companies to pay for and provide the drugs at no cost for those trials. 

“I can easily see cancer death rates even falling by 80 to 90% in 25 years compared to now,” he said. “I predict most cancer will become a chronic disease, managed like we do with other diseases, like diabetes.”

Chip Petricoin can be reached at epetrico@gmu.edu. 

For more information, contact John Hollis at jhollis2@gmu.edu. 

About George Mason 

George Mason University is Virginia’s largest public research university. Located near Washington, D.C., Mason enrolls nearly 40,000 students from 130 countries and all 50 states. Mason has grown rapidly over the past half-century and is recognized for its innovation and entrepreneurship, remarkable diversity and commitment to accessibility. Mason celebrates 50 years as an independent institution. Learn more at www.gmu.edu.