Biomedical Graduate Studies

Description of Research Expertise

Research Interests
The Claiborne lab is interested in understanding the mechanistic determinants of T cell dysfunction in chronic infections such as HIV in order to engineer more potent T cell immunotherapies.

Keywords
HIV, HIV pathogenesis, CAR T cell therapy, T cell exhaustion, humanized mice

Research Details
T cell immunotherapies offer hope for the treatment of malignancies and other chronic diseases. However, natural mechanisms in place to limit immune-mediated pathology ultimately attenuate the T cell response in the setting of chronic antigen exposure, such as is found in chronic viral diseases – including HIV – as well as cancer. A better understanding of the mechanisms underlying T cell exhaustion has the potential to revolutionize T cell immunotherapies, such as chimeric antigen receptor (CAR) T cell therapy, for the treatment of human disease.
The Claiborne lab is rooted in understanding the complex interplay between the virus and the host in HIV transmission, pathogenesis, and persistence. A central focus of the lab is the optimization of CAR T cell therapy for a functional HIV cure. Concordant with efforts to engineer potent CAR T cell therapies against HIV, the Claiborne lab seeks to uncover the mechanisms behind the initiation and maintenance of dysfunctional T cell phenotypes, as the pursuit of these questions is critical to developing the next generation of T cell immunotherapies. To answer these complex questions, the lab leverages the powerful in vivo model system of HIV-infected humanized mice coupled with HIV-directed CAR T cells to study the evolution of antigen-specific T cell function over time.

Rotation Projects

Influence of viral characteristics on HIV-specific CAR T cell function
Previous work by the lab has demonstrated that the intrinsic viral replicative capacity (vRC) of the transmitted/founder virus can greatly impact the disease course of HIV-infected individuals. Individuals infected with high-vRC variants display exacerbated immunopathology characterized by T cell activation and exhaustion, concomitant with rapid CD4+ T cell loss. This may also represent an unrecognized hurdle for a functional HIV cure, as individuals with high-vRC viruses may be more refractory to CAR T cell therapy or other interventions. The lab endeavors to use a previously generated suite of chimeric viruses exhibiting distinct vRC phenotypes to define the extent to which vRC affects CAR T efficacy in vitro and in vivo and to elucidate the mechanisms responsible.

Lab Personnel
Madison Werts (Research Assistant)
Tyler Yang (Research Assistant)
Reyes Acosta (Graduate Student, CAMB)