Francesco R. Simonetti


My research focuses on the persistence of HIV infection and its interplay with our immune system. The development of antiretroviral drugs changed the face of the HIV pandemic, transforming a devastating disease into a manageable chronic condition. However, despite successful treatment, HIV persists, integrated into the genome of infected cells as part of what we call the latent reservoir. Because of this reservoir, therapy must be continued indefinitely, requiring public health systems to deliver medications to all 38 million people living with HIV for life. Thus, understanding the mechanisms of HIV reservoir maintenance is paramount for the development of novel curative strategies.

Previous studies showed that the proliferation of infected CD4+ T cells is a major cause of HIV persistence. In the laboratory of Robert and Janet Siliciano, I tried to untangle which forces drive HIV-infected clones to expand over time and survive. My thesis work demonstrated that immune responses to chronic antigens, such as those from other common viral infections, play a major role in determining the fate of infected cells. In other words, the T cells’ “day job” drives reservoir persistence. In most cases, the HIV provirus is just a passenger. Our work shows that HIV leaves a deep footprint on the immune system, which imposes huge challenges for future therapeutic interventions.

Questions & Answers

Why did you choose Johns Hopkins for your work? When I decided to pursue a Ph.D., my goal was to continue to work on HIV persistence. Robert and Janet Siliciano have been leading this field for more than two decades. Their group provided the first evidence that the establishment of the latent HIV reservoir prevents antiretroviral therapy from curing HIV infection. Working with them was a big dream of mine, and the main reason I decided to join Johns Hopkins. Moreover, the potential for collaborations with the incredible immunologists and infectious diseases experts was something that drew me toward Johns Hopkins. What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received? I am honored to receive this award. It is an important recognition of the hard work of many people in the lab that helped with the project. This award is the culmination of a very exciting journey of both personal and professional growth. What contributed to your project's success? It has been a privilege to work in the Siliciano lab. Robert and Janet allowed me to develop my project with freedom, driven by curiosity and creativity. My clinical training in infectious diseases helped to tessellate different parts of my project and have a translational perspective. The success of my thesis is also due to guidance from my committee members: Andrea Cox, Benjamin Larman and Alison Hill were invaluable mentors. What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins? Students and fellows are the lymph and moving force of our institution. Thus, it is very important to celebrate their efforts, showcase their work and inspire the new generations of trainees. What has been your best/most memorable experience while at Johns Hopkins? Spending time with other scientists and learning about their lives has been incredibly stimulating. One time I had the opportunity to host Charles Bangham, a retrovirologist visiting from Imperial College London. Initially trained to become a clinician, he then dedicated his life to basic and translational research. I asked what led him to that decision since, at that time, I was uncertain about my career direction. He told me: “It was easy, once I stepped inside the laboratory for the first time, I knew I was home.” That encounter made me realize I shared that very same feeling and cemented in me the idea that going back to grad school was the right choice. What are your plans over the next year or so? I am planning to graduate this summer. Over the next year, I would love to continue to work on some exciting projects ongoing in our lab. My long-term commitment is to be an active part of the HIV scientific community. Over the past three decades, the knowledge that we gathered surrounding HIV and its treatment is unfathomable. But there is still a lot of work to do. I want to see, up close, what happens over the next three decades. Tell us something interesting about yourself. What I cherish the most about science is how it makes you wander, and I have a big passion for traveling. I spent the first 30 years of my life in Italy, between Milan and Tuscany, but my research made me move across the pond three times already. Being an avid foodie, adjusting to Baltimore was … a piece of (crab) cake!