There is still no cure for the 38 million people worldwide living with HIV-1, due to the persistence of the virus in a latent reservoir of CD4+ T cells. Efforts to cure HIV-1 infection by reducing the size of this reservoir have focused on the shock and kill strategy, which relies upon inducing viral gene expression and revealing infected cells to the immune system (shock). Infected cells can then be targeted for destruction by immune cytolytic cells (kill). While some chemical agents have induced slight increases in HIV-1 gene expression, reductions in the size of the latent reservoir have not been observed. Critical to the success of shock and kill, then, is the development of novel kill strategies that can enhance the destruction of infected cells. My research in the labs of Drs. Robert and Janet Siliciano and Dr. Scheherazade Sadegh-Nasseri focused on how HIV-1 is recognized by the immune system and whether we could generate reagents that could promote recognition and killing of infected cells. This highly team-based study led to the discovery and production of bispecific antibody engagers that are exquisitely specific and sensitive to minute quantities of HIV-1 peptides presented on the surface of infected cells. These bispecific antibodies, with domains specific for both HIV-1 and cytolytic T cells, enabled robust killing of HIV-1 infected cells, in a manner dependent on the quantity of HIV-1 peptides presented on the infected cell. Given the many millions of individuals affected by this incurable disease, understanding mechanisms that could guide improved immunotherapies for cure strategies is essential.
Questions & Answers
Why did you choose Johns Hopkins for your work? I was drawn to its world class clinical and research training, wonderfully collegial environment and an incredible, curious and inspiring group of classmates. Additionally, I attended JHU [The Johns Hopkins University] for undergrad and had the opportunity to be mentored by several brilliant and caring researchers and physicians. This gave me added confidence that Hopkins would be a nurturing environment to pursue my M.D./Ph.D. training, and so far, it has not only met but far exceeded these expectations. What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received? It is extremely rewarding to receive recognition for the hard work that went into this project, which included contributions from several student trainees and collaborators. I am specifically delighted to receive the Paul Talalay Research Award. Dr. Talalay founded and was the first director of the M.D./ Ph.D. program at Johns Hopkins. I am grateful for his efforts to build a training pathway at Hopkins for those of us seeking to combine clinical and research training, and for his dedication to our program. Receiving this award bearing his name is very humbling! What contributed to your project’s success? (Special skills, interests, opportunities, guidance, etc.) Interesting ideas in science often emerge from conversations involving coffee and food. One such conversation led to very fortuitous collaborations that kick-started this project’s success. This project was an enormous team-based effort that involved dedication from several talented undergraduates and graduate students who I was lucky to work with and learn from throughout my Ph.D. I also benefited from the astute scientific advice of my thesis committee and a great support system composed of my lab mates, friends and family. I was fortunate to have incredible PIs — Drs. Robert and Janet Siliciano and Dr. Scheherazade Sadegh-Nasseri. They gave me the freedom to start a project that was not the major focus or expertise of either lab and move it forward independently. At the same time, they guided me, helped me troubleshoot and kept me inspired. They believed in me and entrusted me with the responsibility of mentoring several students early on in my Ph.D., without whom this work would not have been possible. What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Hopkins? Young Investigators’ Day represents precisely why I feel that Hopkins is a true gem of a place to pursue clinical and research training. There is an incredible emphasis here on nurturing and celebrating the growth of each new generation of trainees, and this serves as an inspiration to younger students starting their training. What has been your best/most memorable experience while at Hopkins? I have experienced many personal and professional milestones while at Hopkins, but one of my most memorable experiences was my thesis defense. This moment represented the culmination of several years of hard work and persistence, along with the ideas and efforts of trainees I had mentored and collaborators who had gone above and beyond to move the science forward. Seeing everything come together at the end was incredibly rewarding. Experiencing the joy and pride of my parents, friends and loved ones as I shared my research was profoundly moving. What are your plans over the next year or so? Graduating, looking for faculty positions, etc.? I am currently finishing my medical training and will apply to residency programs this fall, with the goal of pursuing a physician-scientist career in the future, conducting immunology-based research. Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences? I have lived in Baltimore now longer than anywhere else in my life, but am now re-discovering it from the lens of my son. We love finding small neighborhood playgrounds and parks. His bar is pretty low though — as long as there’s dirt to dig, he couldn’t be happier!