One researcher’s pursuit of rare T cell analysis using flow cytometry
An interview with Dr. Sara De Biasi
Dr. Sara De Biasi from the University of Modena and Reggio Emilia (UNIMORE), Modena, Italy, discusses her work researching invariant natural killer T cells (iNKT) in HIV-positive subjects.
Immunotherapies transform the body’s inherent immune system, elevating its ability to fight cancer. T cells and their mediated responses are central to this transformation. In acquired immunodeficiency conditions such as HIV, T cells are fatally targeted by the virus in a sophisticated effort to hinder the body’s immune system. Scientists like Sara De Biasi are achieving immense insights on the activities and characterization of T cells, specifically invariant natural killer T cells (iNKT) in HIV-positive subjects. Using flow cytometry technology to inch closer to uncovering revolutionary immunotherapies, Sara shares her research journey—one driven by natural curiosity and an early exposure to the mesmerizing interplay between HIV and the immune system.
What drives your passion for science?
I am a very curious person. In every field, I aspire to know how and why something happens—what are the causes, what are the consequences. The more complex it is, the more passionate I become.
What inspired you to pursue this profession?
My childhood dream was to become a medical doctor and perform autopsies. However, I decided to start my studies by gaining a solid background in biology. Thus, I took a degree program in biotechnology. I was so enthusiastic to understand the molecular and cellular mechanisms responsible for an immunological disorder that I realized I had found my way—to this day, it’s still the most appealing aspect of my research.
How did you first become involved in researching acquired immunodeficiencies, such as HIV?
Professor Andrea Cossarizza was my professor of immunology. His enthusiasm was contagious, and I was extremely curious to understand how the immune system works during HIV infection and how HIV kills CD4+ T cells. He was looking for students to carry on HIV research; in particular, the effects and side effects of antiretroviral therapy. I applied and started the day after.
You’re interested in rare populations of T cells and their role in autoimmune diseases. Can you share more?
I have good training and experience in immunology, particularly in the development and use of new flow cytometric approaches. My longstanding research commitments are centered on identifying the molecular and cellular basis and involvement of the immune system in several diseases and infections, such as HIV/AIDS or hepatitis and physiopathological conditions. I have built expertise in the clinical application of new methods for the identification of rare cellular subsets in patients affected by HIV infection and in patients undergoing liver transplantation, as well as in patients suffering from multiple sclerosis. Such methods are allowing a new characterization of the functional activities of these cells.
What challenges do you face in your research?
Every time I am dealing with a new project, there are at least two big things to think about: how to choose the right methodology and how to deal with huge amounts of data. Communication is crucial to achieving knowledge and results, so it’s paramount to feel comfortable reaching out to colleagues for help. Moreover, I work at the university, so one of my activities is to teach students. I explain how to work in the lab and emphasize that productivity is the most valuable quality a researcher should possess. Teaching has been a challenging endeavor; but in the end, I realize that I have empowered potential new researchers and I’m proud of that. In your research journey, you’ve leveraged flow cytometry and continue to be an advocate for this technology.
Can you share more?
Flow cytometry is fast and precise, and it allows the study of several dozens of proteins expressed at a single cell level. The study of rare cell populations is of growing importance. It’s useful not only to understand disease mechanisms, but also to find novel targets. With multiparameter capabilities and a very high analysis rate, flow cytometry is, at present, the most potent technology to address rare cell analysis. When I first studied iNKT cell populations in HIV-positive patients, I had to deal with a more evident paucity of cells (iNKT cells are rarer in HIV, as HIV positive people are immunocompromised). More than 20 million cells should be stained to find these rare populations among PBMCs. Until recently, no instrument was able to acquire 20 million events. Then the Invitrogen Attune NxT Flow Cytometer made my project reliable. The consequence of acquiring 20 million cells was how data should be managed, but powerful computers with many gigabytes solved this problem.
What is ISAC and what is it like being one of their scholars?
The International Society for Advancement of Cytometry (ISAC) aims to advance the impact of cytometry in the sciences. ISAC has a worldwide membership of more than 1,850 scientists. I became a scholar in 2016 and can network with top experts, strengthen my critical thinking and independent approach to science, and develop a solid foundation for my career. Thanks to the scholarship, I obtained the Italian National Scientific Habilitation to become Associate Professor.
How will the work you’ve done impact the research community at large? What’s the potential of applying flow cytometry technology to other areas of research?
The most recent immunotherapies use an approach that reshapes the body’s own immune system to fight dangerous cancer cells that may have disguised themselves or put the brakes on the immune system. The recent immuno-oncology therapies are revolutionizing treatment in some patients with certain types of cancers. In tumors such as melanoma, the results have been even more impressive, but many patients unfortunately will develop progressive disease. Thus, it is important to understand immune checkpoint inhibitors and the molecular mechanisms that lead to the discovery of biomarkers that are likely to predict an individual’s response to therapy.
As for last thoughts to leave us with—what do your potential findings mean in the long term, for those affected by HIV?
HIV patients with a relatively advanced age, e.g., more than 50 years old, can experience pathologies that affect much older non-HIV citizens. Chronic inflammation and immune activation, observed typically in elderly people and defined as “inflammaging,” can be present in HIV patients, who experience a type of premature aging. This relatively new condition is extremely complex. It is important to understand the role of inflammation and immune activation in HIV patients in order to design strategies that can support the most potent approaches.
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