Epigenomic Regulation of HTLV Replication & Pathogenesis

  • CTCF is a chromatin barrier element
  • Single CTCF binding site in HTLV-1 DNA
  • Regulates virus expression and DNA looping
  • Loss of CTCF binding attenuate pathogenesis
HTLV Integration Preference & Lymphomagenesis

  • Role of Protein Phosphatase 2A in HTLV-1 IN binding, virus replication and T-cell immortalization
  • Using virus with mutation in binding sites and cells with CRISPR/Cas9 deletion
Role of T-Cell Receptor Signaling in HTLV-Leukemia/Lymphoma
  • Frequent gain-of-function mutations in TCR pathway in adult T-cell leukemia/lymphoma
  • Ongoing studies of role of PKCβ and IRF4
    •  Proximity analyses of PKCβ
    • CRISPR/Cas9 PKCβ gene
    • IRF4 CUT&RUN Sequencing
    • CRISPRa Screen for IRF4 bypass

HTLV Vaccine

  • HTLV env mRNA vaccine prevents infection in rabbits
  • Efficacy correlates with nAb response
Transcriptomic Analysis of KSHV-Associated Tumors

  • Single cell RNA seq of KS
  • Define role of immunotherapy