A biologist with a master’s degree in Infectiology and Tropical Medicine and a doctorate in Immunology from the Federal University of Minas Gerais (UFMG) in Brazil, Andreia Barroso is currently working as a Postdoctoral Fellow in the Quintana lab through Harvard Medical School and Brigham and Women’s Hospital. Her laboratory, in collaboration with research institutions in Brazil and Argentina, recently produced a publication in Nature Neuroscience, elucidating the molecular mechanisms employed by the Zika virus to cause microcephaly in newborns.
Please tell us about yourself. What did your journey from Brazil to Harvard look like? What challenges did you overcome along the way?
Professionally, I am a biologist with a master’s degree in Infectiology and Tropical Medicine and a doctorate in Immunology. I acquired these titles at the Federal University of Minas Gerais (UFMG), a university in my hometown of Belo Horizonte, Brazil. During graduate school, my curiosity encouraged me to understand and participate in the essence of science, consisting of thousands of procedures and techniques often unheard of by the public. After working in two genetics labs for a short period in 2009, I joined the lab of Dr. Fabiana S. Machado, who had innovative ideas for ways to study the immunology of parasitic diseases, which are a substantial socioeconomic and public health problem in Brazil. Under her mentorship, I studied the role of the highly diverse, or promiscuous, aryl hydrocarbon receptor (AHR) in Chagas’ disease.
Although I have always been deeply fascinated by how simple, microscopic organisms can drastically affect complex beings, the versatility of AHR caught my attention even more. As I was reading papers about the role of AHR in different disease contexts, I came across studies by Dr. Francisco J. Quintana. In 2015, during the Annual Congress of the Brazilian Society of Immunology (SBI) in Brazil, I had the opportunity to watch a lecture by Dr. Quintana. At the beginning of the lecture, he described AHR as a “social molecule” because of its ability to interact with different ligands. This description changed my perspective of AHR as a promiscuous protein to a valuable one with a potential role in disease treatments.
After overcoming my self-doubt, I presented myself to Dr. Quintana and demonstrated my interest in working with him. He agreed to take me into his lab under the condition that I secure my own funding, which proved to be a substantial challenge given the lack of resources for Brazilian doctoral students trying to work abroad at the time. After a year of procuring financial support, I finally obtained funding from the FAPEMIG scholarship and joined the Quintana Lab in 2017. Separate from the initial financial challenges that could have profoundly jeopardized my opportunity to work at Harvard, the other challenges I faced were related to the inexperience of living abroad and living far away from family and friends. Specifically, it was difficult to adapt to a highly competitive and demanding environment as well as to express the most authentic version of me to people whom I didn’t know, but would be spending the majority of my time with. Another challenge worth mentioning was coming to terms with my complicated and multi-layered minority status in North America. Although I did not fully perceive this facet of my identity in Brazil, I have become increasingly aware that I somehow overcame more obstacles to be at Harvard compared to other people from more privileged backgrounds. In this sense, emotional intelligence and strength are the tools I have worked on to overcome these challenges.
What advice would you give to Brazilian students trying to secure a research position at Harvard?
It is not easy to readily give advice because I did not plan to come to Harvard until the year before I secured the position. Something I actively tried to do was take advantage of every professional opportunity that came my way. While I was studying at UFMG, I always attended different events, congresses, and lectures, even if they were not within my field, to expand my knowledge and maintain an open mind. As I described before, the opportunity to work at Harvard presented itself after I introduced myself to a professor whose research I followed. Of course, my CV and references were evaluated, but the initial and effective contact resulted from my willingness to act on an opportunity. A chance!
That being said, the first piece of advice I would give is not to be afraid. Fear is an evolutionary strategy that incites anxiety about the unknown to keep us aware and protected from danger. However, when in excess, fear can paralyze our actions and keep us away from life-changing opportunities. Now, looking back, I see that the simple act of believing that something is possible is also essential. Approach your goal with all your will and energy, and this will boost you with positive actions. These actions might appear very subjective, but in my experience, they were effective and valuable.
Regarding objective actions, I would find and talk to people who have studied/worked at Harvard. The DRCLAS website, as well as the PUB Boston (Pesquisadores Universitários em Boston) website, has a directory for people with this experience who are generally willing to help. Finally, and most importantly, it is essential to find researchers in Brazil who work in collaboration with principal investigators from Harvard. In this case, the chances of being accepted are even higher because both groups are already working together.
Can you summarize the findings in the Nature Neuroscience paper recently published by your lab? How do these findings impact the development of treatments against Zika?
Zika virus (ZIKV) is a “smart” virus that has the mosquito Aedes spp. as the vector for its transmission. The virus is considered “smart” because Aedes aegypti is also the vector for two other endemic viruses: dengue virus and yellow fever virus. Zika infection has been reported since the 1950s; however, the emergence of ZIKV-infected individuals, coupled with increased cases of babies born with microcephaly, made Zika infection a public health concern in 2014. Microcephaly, a compromising brain abnormality that was no longer a public health problem, became a critical concern once it emerged as a consequence of the ZIKV infection. In 2016, our collaborators in São Paulo were one of the groups to prove that, in mice, ZIKV was leading to newborns with microcephaly.
Our recently published work in Nature Neuroscience, with Dr. Federico Giovannoni as the first author, described the direct association of the protein AHR with the ZIKV infection. AHR is a protein that acts as a receptor inside the cell to sensor compounds that can be derived from external sources (e.g., pollutants, vegetables, medicines) or from molecules that are produced by the cell or by commensal microorganisms (e.g., derivatives from amino acids metabolism). This protein has essential roles in controlling physiological processes, including the control of immune responses in different cell types and disease contexts.
Our data demonstrated that ZIKV infection led to increased levels of kynurenine, which is a molecule that originates from the metabolism of the amino acid tryptophan. Kynurenine is one of the ligands for the protein AHR that, when activated in the host in the context of ZIKV infection, limits the host-antiviral responses. From an evolutionary point of view, some bacteria, viruses, and parasites have this intelligent and biologically interesting behavior, which they use to camouflage themselves from the scanning of our immune system or to dampen the host immune response.
The clinical relevance of this study is that we target AHR with nanoparticles containing AHR-antagonists or inhibitors compatible with human treatment to impair the suppression of the host-intrinsic immune response during ZIKV infection. With this approach, we found that when animals were treated with these nanoparticles targeting AHR, the parasite load and the incidence of newborn mice with microcephaly were reduced. Regarding the development of future treatments for ZIKV infection, our approach presents an alternative to classic antiviral drugs and could allow us to control a host antiviral component (IFN-I), which is also crucial for other viral infections. As our next step, it would be extremely relevant if this treatment was tested in more complex non-human primates during ZIKV infection.
What were some of the advantages of conducting collaborative research with labs from both Harvard and Brazil? How were tasks for this Zika project distributed between labs abroad and labs at Harvard?
As I have mentioned before, financial support for science research in Brazil is almost nonexistent nowadays, especially for institutions outside the state of São Paulo. Even during the golden era of science in Brazil, we were substantially behind economically developed countries when it came to technology, equipment, and reagents. With that said, these collaborations are significant because Brazil has highly capable scientific minds that suffer due to limited resources. Partnerships allow us to perform experiments with cutting-edge technology and techniques to answer scientific questions that can add value to humankind, independent of nationality and socioeconomic condition.
In the case of the Zika project, the partnership with institutions from Brazil allowed my lab to utilize the expertise of researchers from São Paulo, who are especially familiar with the mouse model for Zika infection and who actively work with endemic and fresh virus samples. At Harvard, we mainly worked with the in vitro experiments (e.g., stimulations and infections in cell lines), as well as genetic analysis of murine samples produced by the group in São Paulo. In Brazil, the experiments performed were related to the infection of mice under different treatments (what we call in vivo).
Looking ahead, what is on your horizon? Do you intend to continue collaborating with Harvard researchers?
Although life-myopia sometimes makes it difficult to look ahead, I am currently continuing to build my future, and it is definitely in my plans to participate in collaborative projects with the network I am developing here. Being in the world’s center for knowledge is addicting, and for now, I do not plan to leave it behind.
Interview conducted by Jannely Villarreal (A.B. '20), Brazil Office Fellow