Projects
Unleashing CAR T-Cells for Infectious Diseases
Chimeric antigen receptor (CAR) T-cells have revolutionized the treatment of B cell malignancies, but require further improvements to treat solid tumors and infectious diseases like HIV-1. We use immunocompetent in vivo models to understand how CAR T-cells traffic throughout the body, and the role played by tumor and/or viral antigens in promoting or inhibiting CAR T-cell function.
Finding a Cure for HIV
Antiretroviral therapy (ART) has significantly improved the quality of life for people living with human immunodeficiency virus (HIV). However, ART only suppresses the virus: HIV persists in “reservoirs” that reactivate as soon as ART is stopped. We evaluate cutting-edge technologies including lipid nanoparticles, CRISPR gene editing, and cellular immunotherapies that are intended to control or cure HIV without ART. We use preclinical in vivo models to ask questions about where the HIV reservoir exists in the body, and how to effectively “drain” these reservoirs to achieve a cure
Improving CAR T-Cells for Cancer
Heat map showing the proportion of 20 distinct CAR T-cells (V1-V20) throughout the body.
The barriers that we seek to overcome to cure HIV are common to numerous infectious, genetic, and malignant diseases. For example, the immune system may have greater freedom to operate in a liquid tumor such as a leukemia, whereas solid tumors and HIV can effectively evade the immune system by turning immune cells “off.” We are testing how cellular immunotherapies such as chimeric antigen receptor (CAR) T-cells move throughout the body and locate a diseased target cell. To date, we can compare up to 20 different CAR molecules in the same experiment, allowing us to weed out less potent molecules and iteratively improve the most promising candidates.
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