Virginie, who also goes by Virginia, Papadopoulou, PhD, is an Associate Professor with joint appointments in Radiology and Biomedical Engineering. She attended Imperial College London for her Master of Science in Physics and Theoretical Physics and then her PhD in Bioengineering. In this interview, Virginia discusses how her passion for scuba diving and becoming a divemaster and scuba diving instructor led her to her life’s obsession, researching the question of how bubbles form in the body and how they can cause decompression sickness.
Her research revolves around ultrasound and microbubbles, their detection and gas physiology modulation in vivo, and their applications in addressing today’s needs in biomedical disease and human performance applications. Her team has developed a unique ultrasound-mediated biofilm drug delivery platform on the therapy side and achieved exciting in vivo results toward clinical and commercial translation. On the human performance side, her team’s work refining the imaging and analysis of ultrasonically detected decompression emboli for personalized decompression sickness risk mitigation is internationally recognized, with awards from the Undersea and Hyperbaric Medicine Society, the Women Divers Hall of Fame and the Divers Alert Network.
How did you find yourself studying bubbles?
I was born in Belgium to Greek parents. At 18, I moved to London for an integrated four-year master’s degree in physics and theoretical physics. I went into physics, loving all the very abstract theoretical math. But by the end of it, I had decided it was too abstract, even for me. I took one elective on medical imaging and absolutely fell in love with it.
Around the same time, I was completing diving training to become a Divemaster. As part of that training, you must take theory exams. One of the exams was on decompression theory, where they explained how bubbles that form in the body during decompression can cause decompression sickness and how this risk is mitigated in scuba diving through decompression algorithms. As a physics major, I became obsessed with that topic and believed there had to be more to the story. So, I started collecting papers on the side. In my dorm, I had a stack of papers I had collected on scuba diving research, all while doing loop quantum gravity as my master’s thesis, which was pretty far from human physiology. That’s when I knew I wanted to transition to a different field.
I very naively did what all undergraduates do; I Googled to find information about who was studying bubbles in biomedical engineering at Imperial. I came across Professor Mengxing Tang’s lab, which was working on contrast-enhanced ultrasound imaging. This clinically approved imaging modality uses intravenously administered contrast agents, which are actually tiny microbubbles, to get better cardiovascular images with ultrasound. A very different context of having bubbles in the body; you inject them on purpose; they don’t form because of diving. I sent him an email and met with him. He offered me an opportunity for a one-year Master of Research in his lab to determine if a PhD in biomedical engineering was the right direction for me.
Within six months of starting in his lab, I knew I wanted to do this for the rest of my life. I fell in love with research. However, I was missing the environmental physiology component of my education in the lab, so Professor Tang encouraged me to reach out to other people for support. I was extremely fortunate that, at the time, there was a PhD Training Network in Europe. I eventually joined this and trained in the pathophysiology of decompression under a European Union Marie Curie fellowship in Belgium, which complimented my biomedical engineering training from Imperial through conducting human field experiments and industrial and hospital placements.
Does that lead you to your current research now?
By the end of my PhD, I had worked on the question of how bubbles form in the body. How can we detect them? When do they cause decompression sickness? And what are some of the things that we can do to try and mitigate bad outcomes? However, I wanted to learn more about other ultrasound technologies that were being developed in Professor Tang’s laboratory. So, I decided to stay on as a postdoc and transitioned into Imaging. I used contrast-enhanced ultrasound for cardiovascular disease applications and contributed to first-in-human translation studies for ultrahigh framerate contrast-enhanced ultrasound in particular. After that, I wanted to learn this other contrast-enhanced ultrasound technique created in the Dayton lab here at UNC, relying on superharmonic bubble detection, so I contacted Professor Paul Dayton. I knew his lab was also working on gas delivery with ultrasound and microbubbles, which I thought could tie in with my interests in gas physiology and diving. I moved to the United States in 2016 to pursue a biomedical engineering postdoc in the Dayton lab here at UNC and NC State University.
While in the Dayton Lab as a postdoc, I transitioned into therapeutic ultrasound. Some of the things I worked on included using oxygen microbubbles and seeing if we could use those to reoxygenate tumors before radiation therapy. 2017, I transitioned to research faculty, still in BME and with Professor Dayton’s lab. I started building my team, received independent funding, and took on more leadership within the lab as Dr. Dayton became the head of the BME department.
As a faculty member, I have looked at topical drug delivery, being able to use ultrasound to permeate biological barriers. In collaboration with Dr. Sarah Rowe in Microbiology, our latest project investigates how ultrasound and acoustically active agents can enhance antibiotic delivery in biofilm bacterial infections in chronic wounds. We’re still doing a lot of human performance with diving research. We’re optimizing how we can detect the bubbles in that context and automate how we analyze this data type with machine learning. And we are also doing image-guided drug delivery with ultrasound for clinical applications. It’s all ultrasound and bubbles but in two different contexts: on the human performance side, healthy human beings in an extreme environment that doesn’t support life without additional engineering protections, where it’s all about disease prevention, and on the medical applications side, the patients with specific pathophysiology that we are trying to treat.
What attracted you to form your lab and team and join the Department of Radiology?
As I built my research program and team over the last 5 years, I have become increasingly interested and involved in efforts to support the research workforce, particularly in undersea medicine and performance. Training the next generation to conduct research in extreme environments using state-of-the-art engineering and biomedical imaging techniques is crucial. In 2006, undersea medicine as part of the Department of the Navy was established as a National Naval Responsibility (NNR), recognizing its importance for the Department of Defense. With support from the Office of Naval Research and the Undersea and Hyperbaric Medicine Society, I am involved in efforts to attract, train, and retain a dedicated STEM workforce in this area. This past year, I also served on the committee of the National Academies of Science, Engineering, and Medicine’s 2024 workshop “Emerging Technology to Address Naval Undersea Medicine Needs,” which constituted a consequential effort to review the state of the field, advances, and future directions since the last effort 20 years ago.
As a study of regulatory mechanisms to external stressors, environmental physiology is inherently interdisciplinary and at the intersection of normal physiology and pathophysiology. It is particularly timely in the context of global climate change for preserving health in increasingly altered environments. The Triangle area in NC has a rich history of scientific discovery and societal impact in this field with Duke’s Center for Hyperbaric Medicine and Environmental Physiology and the Divers Alert Network foundation, both of which I collaborate with. Establishing my new independent laboratory at UNC, jointly between Radiology and Biomedical Engineering, will help solidify this link between BME and clinical applications and offer unique translational research resources. In my new role as Associate Professor, I will be developing a new graduate-level class for BME, “Introduction to Biomedical Ultrasound,” starting in January 2025, and taking on more leadership roles in the STEM education efforts I have already been working on with scientific societies and other stakeholders. Eventually, I would like to secure a graduate training program grant to establish environmental physiology as a biomedical imaging discipline for human performance.
What is one thing you wish your co-workers knew about you before they met you?
One thing that I’d like my colleagues to know is that I enjoy collaborative and interdisciplinary research. I’ve done a lot of it in the past. Speaking the same language with our collaborators is essential, especially in basic science and medical research. There are a lot of things that can be lost in translation. So, the ability to integrate the two worlds is critical. I look forward to working more with my new colleagues in Radiology, as well as my current ones in BME, as we transition ultrasound preclinical technologies to the clinic. As we get to know what their clinical workflow looks like daily, observing how they train their medical fellows, how they interact with patients, and where some of the bottlenecks are there may be opportunities for us to assist and propose new solutions.
If you could give your younger self advice, what would it be?
My advice would be to follow your interests. Many people who finish their undergraduate studies think that the next choice in their career path is make or break. That it’s now or never and that the next decision is final. That can be paralyzing. Of course, it’s an important decision, but there are many ways to get to the same place by taking different routes. You could have different job titles or work in different companies or industries and still rely on the same core competencies or topics you like. To a larger extent now, I’d advise following something you’re genuinely interested in and trusting that things will fall into place. I like to challenge my trainees to be curious and experiment – we’re scientists after all. They can explore various paths to some extent, at least during their time at UNC, by seeking internships or interactions with others in different fields and industries.
What profession did you want to be when you were a kid?
I wanted to be a detective. I would read detective novels in any language all summer long. When I announced that I would be a researcher, my family was not surprised. They were like, well, this makes perfect sense. They could see the jump from detective to researcher.
If you could pick the brain of someone alive or dead, who would it be and why?
As an avid scuba diver, my answer must be Jacques Cousteau. Cousteau was a French naval officer, oceanographer, filmmaker and author. He co-invented an underwater breathing apparatus, which gave birth to the scuba technology of today. People who have done undersea exploration and especially going to places that have not been explored before, that thrill of doing something that no one else has done fascinates me. I’ve read a lot of biographies of people who have done similar things in extreme environments. So, my answer would be to talk with some of them, especially Cousteau.
What do you do when you aren’t working?
When I’m not working, I’m with my family, including my husband and two boys. We go on walks and enjoy kid-friendly activities around the area. We appreciate living in such a family-friendly area with many things to do, which has been a blessing.
How would you describe yourself in one word?
Curious
If you could have one superpower, what would it be and why?
In the past, I would have said something like breathing underwater or the ability to see inside the body, which is significantly related to my research topics.
But now, I want the superpower to act as a springboard for others. I want everyone who comes onto our team to leave the team much better than when they arrived. I have been incredibly fortunate in my career to have incredible mentors who have been really generous with their time and advice and have often acted as sponsors. Now that I’m establishing my own lab, I try my hardest to continue to do that and offer them the same opportunities I was lucky to have while training. I take a lot of time getting to know the students and what they want. Our lab offers a lot of opportunities to explore different research areas. So, depending on their interest, I try hard to tailor their experience, especially for members who will spend a longer time working with our team. I work to match them with what they’re interested in so that they gain the most out of the experience, and we revisit and adapt plans as their interests and skills evolve. I feel happiest if the people who leave the team feel like they benefit from being in this environment.
