Mentoring in patient-oriented research to finding a cure for HIV-1 infection

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Abstract Dr. Lichterfeld is an infectious disease physician-scientist with a strong record of mentoring research fellows in high-profile, patient-oriented research studies related to HIV-1 cure and eradication. He conducts a broad and diverse research program of patient-oriented studies that include molecular and cellular immunologic studies with patient-derived cells, translational human investigations and interventional clinical trials designed to explore novel therapeutic approaches to reduce HIV-1 reservoirs. These research activities provide attractive and exciting training opportunities for physicians and scientists interested and invested in developing strategies for a functional or sterilizing cure for HIV-1 infection; in the past, several of his mentees and co-mentees have progressed to receive R-level funding, and have been offered independent faculty positions at highly-selective universities around the world. In the proposed K24 application, Dr. Lichterfeld will extend and expand his successful mentoring activities in the context of three cutting-edge research areas: He will mentor trainees in the conceptualization, design, implementation and conduct of interventional clinical trials designed to explore novel therapeutic strategies for HIV-1 eradication (Specific Aim 1). These activities will initially focus on an already ongoing, NIAID-funded clinical trial in which Dr. Lichterfeld serves as the PI, but will be expanded in the future to translate novel ideas and concepts into exploratory, proof-of-concept clinical trials. These studies take advantage of advanced clinical trial research infrastructure and a highly motivated HIV-1 patient population at the Brigham and Women’s Hospital and the Massachusetts General Hospital, the two hospitals Dr. Lichterfeld is affiliated with. In addition, Dr. Lichterfeld will train his mentees in innovative next-generation sequencing and proteomics approaches involving single-genome, near full-length viral sequencing, combined with viral integration site analysis, chromatin accessibility assays and chromatin immunoprecipitation assays to profile residual viral reservoirs in patient-derived cell samples at an unprecedented breadth (Specific Aim 2). This work will be facilitated by unique technical resources and cross-disciplinary collaborations at the Ragon Institute and the Broad Institute of MIT and Harvard, where Dr. Lichterfeld holds Associate Member status. Finally, Dr. Lichterfeld will offer a distinct training experience in pediatric HIV-1 infection, focusing on the development of interventions that may enable a long-term, drug free remission of HIV-1 infection in neonates from Botswana (Specific Aim 3). These collaborative investigations will be performed in the context of ongoing, NIAID-funded clinical trials investigating effects of standard antiretroviral therapy and broadly-neutralizing antibodies on viral reservoirs and antiviral immune responses in HIV-1-infected infants started on therapy within the first days after birth. Together, these studies provide distinct but interrelated training opportunities for physicians and scientists to acquire the knowledge, skills, creativity and collaborations that are needed for an independent career in patient-oriented studies focused on finding a cure for HIV-1 infection.