Immune effector cell differentiation & protective host responses against microbial pathogens and tumors in vivo
We have three funded research themes in the laboratory that focus on:
1. The functional differentiation of naive and memory CD8+ T cells: we have built experimental systems in mice to assess the roles of cognate antigen in the functional fates of memory CD8 T cells and their ability to mediate host protection. Our goal is to provide a comprehensive understanding of i) how to generate functionally and epigenetically distinct memory CD8 T cells and ii) how to harness memory CD8 T cell protective mechanisms to the benefit of the host for new T cell therapies.
2. Immunity to malaria: we investigate i) the mechanisms of severe malaria, focusing on the role of type I interferon promoting poor clinical outcomes. We study a functional cell/cell interaction that occurs between macrophages and plasmacytoid dendritic cells in the bone marrow of infected mice and accounts for type I IFN production. We also investigate ii) the role of a subset of circulating memory CD4 T cells we found expanded in Malawian patients clinically protected against Plasmodium falciparum using cytometry by time of flight (CyTOF). We are conducting high throughput "omic" approaches to reveal and functionally test the CD4 T cell program associated with clinical protection against this number one killer parasite worldwide.
3. Anti-tumor immunity: we are using and characterizing a novel stem-cell based model of breast cancer in which several clinically relevant mutations have been introduced. This model mimics several key aspects of highly aggressive human breast cancers. We investigate mechanisms of immune escape and anti-tumor therapies. We are also exploring the immune response in the context of acute T cell lymphomas in HTLV1+ patients,
Our laboratory has developed multiple tools (pathogen, mice), as well as cutting edge approaches that include transcriptomic, single cell transcriptomics, epigenetic and intravital microscopy in close collaboration with other groups at Einstein. Our overall goal is to improve our fine understanding of the factors that orchestrate antimicrobial and antitumoral host protective immune responses in vivo. We believe that our work will contribute to more rationale design of immune cell-mediated preventative and therapeutic strategies.
Current laboratory members:
- Nicole Couturier, Ph. D. Student
- Erik Guillen, M.D./Ph. D. Student
- Jennifer Enright, Ph. D. Student
- Richard Garcia-Betancourt, Ph. D., Postdotoral Fellow
