Tocheva Lab
Principal Investigator: Anna S Tocheva
Institution: Icahn School of Medicine at Mount Sinai (New York, NY)
Primary Subfield: Genetics/Genomics
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
ABSTRACT T cell activation initiates a program of differentiation that generates a continuum of different memory T cell states with diverse functional and molecular profiles. Activated T cells upregulate the inhibitory receptor programmed cell death protein 1 (PD-1) to prevent excessive T cell inflammation, autoreactivity and tissue damage. Upon binding to its ligands, PD-1 interferes with the phosphorylation cascade that modulates the quality and quantity of T cell signaling. Cancers evade T cell recognition by engaging PD-1 and consequently PD-1 blocking antibodies restore anti-tumor T cell responses and improve the survival of patients with various malignancies. Unfortunately, the majority of cancer patients do not respond to PD-1 blockade and up to 30% develop inflammatory toxicities highlighting the critical role of PD-1 in the maintenance of immune tolerance. Research into basic PD-1 biology, together with the clinical picture of cancer patients treated with PD-1 blocking antibodies, converge to emphasize that PD-1 engages complex signaling networks to support T cell homeostasis, differentiation and immune responses. Therefore, elucidating the signaling cascades and molecular…
Active NIH Awards
- 5R35GM150989-04: Molecular mechanisms underlying T cell resistance to PD-1 signaling (2026)
- 5R35GM150989-03: Molecular mechanisms underlying T cell resistance to PD-1 signaling (2025)
- 5R35GM150989-02: Molecular mechanisms underlying T cell resistance to PD-1 signaling (2024)
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