Frenkel Lab
The Frenkel Lab’s research focuses on several areas:
- Understanding the mechanisms that allow HIV to persist during antiretroviral therapy (ART). Our goal is to better enable interventions to cure HIV infection.
- Developing a practical, affordable test – called a point mutation assay – for detecting drug-resistant HIV
- Providing insights into reservoirs of drug-resistant HIV
- Pathogenesis of HIV disease. Specifically, we investigate why HIV-infected individuals experience morbidities and die at younger ages even despite ART.
Over the past 30 years, our group, in collaboration with colleagues in Kenya, Mozambique, Peru, South Africa, Thailand, Uganda and the United States, has conducted studies to address practical questions related to the prevention of HIV-1 infection in infants, mechanisms leading to HIV-1 shedding in breast milk and genital tract of adults, treatment of drug-resistant virus and mechanisms underlying the persistence of HIV infection despite effective antiretroviral treatment. Additionally, we have developed economical assays to improve the management of HIV infection accessible to resource-poor communities.
When studying transmitted resistance from HIV-infected mothers to their children, our group uncovered laboratory errors that refuted the concept of transient HIV infection occurring in infants (Science, 1998, PMID9582120). Findings from this study underscored the importance of meticulous Laboratory Quality Assurance in research. Our group has operated a CLIA Laboratory for >18 years primarily performing assays NIH IMPAACT Network.
Our laboratory located within Seattle Children's Research Institute found evidence and later provided proof that proliferating cells have a major role in sustaining the HIV reservoir despite effective treatment (J Virol, 2005, PMID16014925) (Science, 2014, PMID25011556). More recently we have shown that HIV-infected clones fuel persistent low-level viremia during antiretroviral treatment (ART) and rebound viremia following ART suspension (PLoS Pathog, 2020, PMID32841299). We described that HIV is integrated disproportionately into genes that control immune functions, the cell cycle, cancers or pathways controlling T-regulatory cells (J Infect Dis, 2017, PMID28520966) and other pathways depending on if ART is initiated during acute or chronic HIV-1 infection (J Clinic Invest, accepted 2023). These finding led to investigatiions of HIV-1 integration on CD4 cell function (J Immunol, 2022, PMID35264460) and current projects focused on (1) effects of integrated virus on high-risk HPV cervical infections, and (2) immune tolerance in HIV infected infants.
Our research on HIV drug resistance has defined reservoirs and effects of mutant codons (Clin Infect Dis, 2010, PMID20377404) and the utility of point mutation assays in screening to diagnose HIV drug resistance (Lancet HIV, 2019, PMID32386719). Our current studies aim to (1) define the mutant codons associated with failure of dolutegravir-based treatments, (2) develop inexpensive assays to detect these mutations in low-resource settings (EBioMedicine, 2019, PMID31767540 and AIDS, 2020, PMID32205723), and (3) define the risk of genotypic HIV resistance for mother-to-child HIV transmission and treatment outcomes (Clin Infect Dis, 2021, PMID34467974).
For a listing of our published research please access MyBibliography.
Investigator Biography
Lisa M Frenkel, MD
Dr. Lisa Frenkel is an internationally recognized expert on HIV and infectious disease. She is co-director of the Center for Global Infectious Disease Research at Seattle Children's Research Institute; professor of pediatric infectious diseases, laboratory medicine and global health at the University of Washington; and co-director of Seattle Children's pediatric infectious diseases and virology clinic.