The history of HIV research is marked by great successes and disappointing failures. Since the initial description of Acquired Immunodeficiency Syndrome (AIDS) and its etiologic agent, Human Immunodeficiency Virus (HIV) in the early 1980s, it took less than ten years for the first antiretroviral drug to be approved and introduced into clinics. Antiretroviral therapy (ART) has transformed HIV infections from an almost certain death sentence to a manageable chronic condition with typically minimal symptoms and negligible drug toxicity. Unfortunately, ART does not affect latently-infected cells, which lack viral replication and can remain dormant for years or even decades, thus eventually cause spreading infections after discontinuation of therapy. These latent cells, known as reservoirs, must be neutralized to provide a true cure for HIV infection. To date, all attempts to achieve this goal, despite initial success, have largely failed in clinical trials. For the majority of patients, complete remission remains out of reach.

New means to identify and target latently infected cells need to be explored full steam ahead. The goal of our research is to better understand latent HIV reservoirs and develop strategies to impact either reservoir seeding, maintenance (survival), or reactivation from latency. In addition, we are interested in the pathogenesis of HIV infection and the molecular mechanisms involved in disease progression.

To this end, we use high-dimensional systems virology and CRISPR methods to first comprehensively characterize and then study reservoir cells in detail. Our model systems include cell line- and primary cell-models of HIV latency and virus-induced pathogenesis, but we also study samples from HIV-infected patients.

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​Research Statement: The ultimate goal of our work is the development of an effective and scalable cure for HIV infected individuals. In order to achieve full remission, we believe that such approaches will likely have to be multifactorial, comprising reservoir reduction (REDUCE) and subsequent silencing of residual, latent proviruses (CONTROL). Additional immunologic manipulations might be necessary to prevent viral rebound and disease progression. A prerequisite for devising potent cure strategies is an in-depth understanding (CHARACTERIZE) of the exact nature of latent reservoirs (localization, cell type, immunophenotype, etc.).