We study immune responses, broadly speaking, but are most interested in the development and functions of T cells, a component of the immune system that is required for control of infections. We are specifically interested in CD4+ T cells, which in humans are the target of HIV, and are critical for most adaptive immune responses.

We have a comprehensive approach to research. Researchers in the lab integrate experimental approaches, including single cell and tissue “omics” analyses (which are a major focus of the lab), genetics, in vivo  models of infection and tumor, and bioinformatics, e.g. modeling gene regulatory networks (1).

Current research is directed at three questions.

1-CD4⁺ T cell development in the thymus. Building on the laboratory’s long-standing interests (2), ongoing research investigates new signals or factors that direct CD4+ T cell development, and mechanisms that mediate the function of Thpok, a transcription factor required for the development of CD4⁺ T cells in the thymus and their post-thymic functions (3).

2-CD4⁺ T cell responses to infection and tumor. These studies have become a major area of focus in the laboratory. Using single-cell RNAseq and ATACseq, we recently characterized CD4⁺ T cell responses to infection (4-6) or tumors (7). Current research leverages newly developed experimental models to compare how CD4⁺ T cells control chronic infections and tumors, and to design strategies to harness their anti-tumor potential.

3-Role of the thymus in immune tolerance. Maintaining immune homeostasis, including tolerance to self-antigens and commensals at mucosal barriers, is a critical function of T cells. Recent (1 , 8) and ongoing studies investigate how the thymus contributes to tolerance through the deletion of self-reactive T cell precursors and generation of T cells with immunoregulatory functions.

Cited publications

1.         L. B. Chopp et al., An Integrated Epigenomic and Transcriptomic Map of Mouse and Human αβ T Cell Development. Immunity 53, 1182-1201.e1188 (2020).

2.         G. Sun et al., The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection. Nat Immunol 6, 373-381 (2005).

3.         Y. Gao et al., NuRD complex recruitment to Thpok mediates CD4(+) T cell lineage differentiation. Sci Immunol 7, eabn5917 (2022).

4.         M. S. Vacchio et al., A Thpok-Directed Transcriptional Circuitry Promotes Bcl6 and Maf Expression to Orchestrate T Follicular Helper Differentiation. Immunity 51, 465-478.e466 (2019).

5.         T. Ciucci et al., The Emergence and Functional Fitness of Memory CD4(+) T Cells Require the Transcription Factor Thpok. Immunity 50, 91-105.e104 (2019).

6.         T. Ciucci et al., Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells. J Exp Med 219,  (2022).

7.         A. Magen et al., Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells. Cell Rep 29, 3019-3032.e3016 (2019).

8.         J. Nie et al., The transcription factor LRF promotes integrin β7 expression by and gut homing of CD8αα(+) intraepithelial lymphocyte precursors. Nat Immunol 23, 594-604 (2022).