By Veronica Villanueva
Dr. Best-Popescu is an exceptional scientist at the University of Illinois at Urbana-Champaign. She is an Assistant Research Professor and the director of the Cellular Neuroscience Imaging (CNI) Lab in the Department of Bioengineering. Dr. Best-Popescu’s research interest is in studying the intersection of brain structure, function and disease across the nano to cm scale. To do this she compares healthy non-disease states and murine disease models using a unique type of Quantitative Phase Imaging (QPI) called Spatial Light Interference Microscopy (SLIM). What’s fascinating about her research Best-Popescu says, is that “we fight disease all the time, and we usually win.” She wants to understand mechanisms of disease, susceptibility and resilience to better fight disease.
Dr. Best-Popescu, like many Scientists of the Month, grew up with excellent science teachers, who inspired her scientific curiosity. She went to school at Comberton Village College, and then Hills Road Sixth Form College in Cambridge, England where she had many unique and exciting opportunities to study human physiology, histology, chemistry, computer science C++, business, and art, which provided her with a wide breadth of knowledge and led her to value an interdisciplinary approach to research. During her undergraduate studies, Dr. Best-Popescu double majored in biochemistry and psychology at UMASS, and after graduating, all she really knew was that she wanted to work in a laboratory fighting disease. The Sunday Boston Globe was full of exciting hospital jobs, but they all required American Society of Clinical Pathology (ASCP) certification. Fortunately, this led Dr. Best to Northeastern University and straight into Dr. Mike Laposata’s lab. He was the Director of Clinical Laboratories at Massachusetts General Hospital. The work studying fatty acid profiles in diseases such as cystic fibrosis and bipolar disorder was fast paced and exhilarating, and the experience altered her career and life path forever. Dr. Laposata was a fantastic mentor. He loved what he did, and he encouraged Best to get her PhD in his lab, and to take advantage of every opportunity. Her PhD research focused on investigating the pathobiology and clinical relevance of Fatty Acid Ethyl Esters (FAEE), byproducts of alcohol consumption, to heavy drinking and organ disease. She used red blood cells (RBCs) as a model physiologic membrane hypothesizing that over time, with heavy persistent drinking, these hydrophobic FAEE were intercalating and accumulating within cell membranes – both neural and RBC – where they caused membrane rigidity. The idea was that tolerance to alcohol may be caused by FAEE-induced altered receptor trafficking to membrane surfaces. Lipid rafts were a hot topic at the time. However, there were few readily available physiologically relevant techniques to measure membrane rigidity, and no techniques to image living cells over time. Luckily for Dr. Best, pursuing solutions to these problems led her to two amazing collaborations. She landed a two-year visiting research scientist job at Harvard School of Engineering and Applied Sciences, working with Howard Stone on RBC elasticity measurements in glass microchannels, and she started a collaboration with Gabriel Popescu and Michael S. Feld’s group in the George R. Harrison Spectroscopy Laboratory at MIT. Popescu had developed a new QPI microscopy technique called Hilbert Phase Microscopy that could measure live cell membrane dynamics in real time, and over time. Popescu had trouble keeping the RBCs alive, and Best had struggled for years trying to measure biophysical changes in living cells. Having experience and insights from different disciplines – physics and biomedical science – allowed them to solve research problems, and the hurdles that had previously stifled their progress disappeared almost instantly. They continued to work on the remarkable deformability of red blood cells and published numerous papers together.
Sharing exciting work and common interests, the two ended up falling in love, getting married, and eventually having two children. They left Boston when Dr. Popescu (Gabi) got his dream job in Electrical and Computer Engineering at the University of Illinois at Urbana-Champaign. Dr. Best got a job at UIUC’s legacy College of Medicine teaching Clinical Neuroscience to first year medical students, which she did for ten years, receiving many awards for excellence in teaching. In 2014, she joined the Department of Bioengineering and started her Cellular Neuroscience Imaging Laboratory at the Beckman Institute for Advanced Science and Technology.
While her path in life has been full of opportunities, luck and success, Dr. Best-Popescu has encountered times of struggle and hardship. When she was getting her PhD, her mother was diagnosed with stage four adenocarcinoma of the lung. Against advice from all trusted advisors, who worried that people who dropped out of the doctoral pipeline never return, she put her PhD on hold, knowing that every minute she could spend with her mom was important. Her experience at MGH and familiarity with how to do clinical research allowed her to do a meta-analysis of chemotherapeutic agents, and she found an early experimental compound, ZD 1839, that prolonged her mother’s life from the two week prognosis she was given at diagnosis to just over two years, which was unheard of for people with stage four adenocarcinoma at that time. Losing her mother was devastating but through her hope, knowledge and experience in the field, she was able to have a lot more time with her mom.
Tragically, Gabriel Popescu passed away in 2022. Dr. Best lost her work partner, her husband and the father of her children, and UIUC lost a leader in biophotonics and quantitative phase imaging fields. Early this year, Dr. Best lost Jingfang Zhang (Kelly), one of her PhD students, to cancer. “Life definitely happens” Dr. Best-Popescu said, meaning that loss and the challenges that come in its wake affect everyone, and interrupt our most optimistic plans. Part of Best-Popescu’s resilience came from continuing their shared scientific mission.
Dr. Best-Popescu has continued using QPI in her research investigating neurological health and disease pathways. She and her graduate student Jorge Maldonado De Jesus developed a novel, fast, inexpensive, machine learning enabled QPI technique that measures and maps mouse brain cell and tissue organization across several linked scales. The technique allows for the direct analysis of neuroanatomical differences between healthy and disease sample groups. In the future, they hope to coordinate their single cell morphotype distribution cartographs with other brain spatial genotyping and lipidomic platforms. In addition to histopathological studies, the CNI lab uses SLIM to measure Glioblastoma (GBM) brain cancer treatment resistance and efficacy. SLIM uses white light and no labels which means the imaging technique is so friendly to cells that you can image over long periods to directly observe the effects of radiation and other treatment paradigms on GBM and healthy cells. She says “Gabi would be proud of their progress.”
Dr. Best-Popescu continues to collaborate with many scientists at UIUC and from other institutions. This keeps her research exciting and up to date. She works with an interdisciplinary group of women scientists including Dr. Yang Zhao from Electrical and Computer Engineering, Dr. Sara Pedron Haba from Chemical and Biomolecular Engineering, Dr. Kimberly Selting, a Veterinary Clinical Medicine radio oncologist, Dr. Chitra Subramanian from Biomedical and Translational Sciences and Dr. Suguna Pappu a neurosurgeon. We all come with different areas of expertise, different tools and perspectives to cure GBM.
When I asked Dr. Best-Popescu about advice she had for our AWIS audience, she laughed and said “it’s hard to give advice when you have a history of not taking advice.” Early in her career she was advised not to get married as it would detract from her scientific endeavors, and later, when her daughter was three months old, she was told “if you want to be successful, don’t expect to see Sophia until she’s eighteen.” Best thinks that in the end, to be successful, you have to make hard personal decisions and be true to yourself. She wouldn’t trade her path for any other. And despite the losses, she feels truly lucky: “when I go to work, I love what I do, and here I am in my laboratory fighting disease!”
Then she added that the advice she could give is first, read! Reading is critical in science and in life; it is how we learn and imagine, but it is often undervalued. Second, develop a close circle of friends that can understand and support your work, while you support theirs. Developing a community helps you survive in academia. Finally, she said, be ambitious and proactive. Define actionable goals for your career advancement, find good mentors, and remember the fundamental ethos of science in service to humanity. This is also great advice for life.