We investigate how HIV genetic diversity drives persistence, drug resistance, and treatment outcomes by integrating computational analysis with innovative sequencing approaches to uncover actionable insights for improving patient care and cure strategies.
Our research focuses on how HIV genetic variation shapes viral persistence, transcriptional activity, and drug resistance, with the goal of linking viral genotype to clinically meaningful outcomes. A central theme of our work is that viral diversity within and across individuals influences reservoir composition, assay performance, and interpretation of clinically relevant viral features. To address these questions, we develop and apply experimental and computational approaches that interrogate HIV genomes, integration sites, and transcripts at high resolution.
Our work has helped establish sequencing-based methods to characterize proviral landscapes, including near full length intact proviral sequencing, or FLIP seq, to distinguish intact and defective genomes (Lee GQ 2017 JCI; Lee GQ 2019 Nat Comm). We also contributed to methods that capture proviral genomes together with integration sites (Einkauf 2019 JCI). More recently, we developed PRISM-seq for sensitive mapping of HIV integration sites from low input samples (presented at CROI 2026). In parallel, we are advancing transcript profiling approaches to study viral splice isoform diversity (presented at CROI 2026).
Using these tools, we investigate HIV drug resistance, reservoir genetics, viral diversity, and transcription in global cohorts spanning multiple HIV subtypes. We also develop bioinformatics methods to evaluate assay performance in the setting of viral polymorphism and sequence diversity.
Biography
Dr. Guinevere Q. Lee is a molecular virologist and Assistant Professor of Medicine at Weill Cornell Medicine. Her research asks how RNA virus genetic variation shapes viral persistence, drug resistance, and response to therapy, with a particular focus on HIV. By integrating computational and experimental approaches, her work aims to uncover fundamental principles of viral evolution that can be translated into improved diagnostics and treatment strategies. She develops innovative bioinformatics tools and sequencing assays applied to global cohorts to link viral genetics with clinical outcomes. Dr. Lee earned her Ph.D. from the University of British Columbia and completed postdoctoral training at the Ragon Institute of MGH, MIT, and Harvard.
Distinctions:
Nature Communications Editor’s Highlight Best 50 Recent Paper (2024)
NIH Martin Delaney REACH Collaboratory Paper of the Year Award (2024)
CROI Young Investigator Award (multiple years)
International AIDS Society HIV Cure and Cancer Forum Scholarship (2017)
Canadian Association for HIV Research Mark Wainberg Fund Award (2018)
Kellen Junior Faculty Award (2020)
NIH and Industry Research Funding (R01, R21, and Merck Investigator Studies Program)
