Remy Bosselut, M.D., Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 37, Room 3032A
- Bethesda, MD 20892-4259
Our lab's focus is on the transcriptional control of CD4+ T cell development and function. We are specifically interested in the transcriptomic programs controlling the emergence of CD4+ lineage in the thymus and in the transcriptional control of CD4+ T cell responses to pathogens and tumors.
Areas of Expertise
1) T lymphocyte 2) T cell development 3) T cell effector differentiation 4) transcription 5) chromatin
We study the differentiation and function of T lymphocytes (T cells), and specifically of CD4+ helper T cells, which are essential for immune responses. CD4+ lymphopenia underlies infectious complications and death in HIV-induced immunodeficiency, and is a chief cause of morbidity and mortality after myeloablative cancer chemotherapy. In addition, CD4+ T cells are involved in tumor control and clinical studies have established their potential as anti-tumor agents. CD4+ T cells typically recognize peptide antigens bound to class II Major Histocompatibility Complex molecules (MHC-II). Together with CD8+ T cells, which recognize MHC-I bound antigens and differentiate into cytotoxic effectors, they form the bulk of T cell populations in lymphoid organs and tissues.
Current research focuses on three key areas.
1) CD4+ helper T cell development in the thymus. CD4+ T cells differentiate in the thymus from CD4+CD8+ “double-positive” thymocytes that have received positive selection signals from MHC-II-peptide antigens. We are investigating how the transcriptomic and epigenomic program characteristic of CD4+ T cells is established in these precursors. This includes studying the mechanisms of action of the zinc finger transcription factor Thpok, which is necessary for intrathymic CD4+ T cell development and for the continued integrity of mature CD4+ T cells. Additionally, we are using a combination of high-throughput gene expression analyses (including single-cell RNA sequencing) and genetic approaches to identify new transcription factors and signaling pathways involved in the emergence of the CD4+-specific transcriptome.
2) Transcriptional control of the “fitness” of CD4+ T cell responses. We recently found that the transcription factor Thpok is necessary for the emergence of memory CD4+ T cells during infection, and for their function during recall responses (Ciucci et al, Immunity, 2019). Our studies in this field integrate gene expression analyses and genetics (including Crispr-Cas9 genome editing) to decipher the transcriptional network that controls the functionality of CD4+ T cell responses in acute and chronic infection models.
3) CD4+ T cell responses to cancer. Even though most current tumor immunotherapy strategies rely on cytolytic CD8+ T cells, CD4+ T cells are attractive tools to treat cancer because of their diverse functions, including cytokine production (e.g., IFN-gamma), help to CD8+ T cells, or impact on blood vessel permeability and angiogenesis. However, subsets of CD4+ T cells, including regulatory T cells, can restrain anti-tumor immunity and promote tumor growth. We are developing experimental models to understand the function of CD4+ T cells in the tumor micro-environment and to design strategies to harness their anti-tumor potential.
The Emergence and Functional Fitness of Memory CD4(+) T Cells Require the Transcription Factor Thpok
How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function
Remy Bosselut, M.D., Ph.D.
Dr. Remy Bosselut trained at the Institut Curie in Paris, France. He earned his M.D. degree in 1992 from the Xavier Bichat School of Medicine and his Ph.D. degree in 1993 from the University Denis Diderot, both in Paris. Dr. Bosselut obtained postdoctoral training at the NCI Experimental Immunology Branch and joined the Laboratory of Immune Cell Biology in 2000.
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