Research

The Ni Lab has three ongoing research projects:

Small molecule CCR4 antagonists in cutaneous T cell lymphoma (CTCL)

CC chemokine receptor 4 (CCR4) is highly expressed on CTCL cells and serves as a great therapeutic target. Mogamulizumab, an FDA-approved anti-CCR4 antibody, has been shown effective for treating SS/MF (Blood, 125(12):1883-9, 2015; Clin Cancer Res, 21(2):274-85, 2015). However, its side effects related to deletion of CCR4⁺ regulatory T cells (Treg) have recently drawn attention. Thus, more effective and less toxic CCR4-targeted therapies are needed. Small molecule CCR4 antagonists have been studied in diseases where CCR4⁺ Th2 cells and Tregs are involved, but no study has been done in CTCL. Our group is assessing the effects of two classes of small molecule CCR4 antagonists in CTCL cells in vitro and in vivo. The preliminary data are encouraging and suggest that small molecule CCR4 antagonists may serve as an alternative way to target CCR4⁺ CTCL cells.

Characterization of tumor microenvironment in advanced skin lesions of cutaneous T cell lymphoma (CTCL) by image mass cytometry

Imaging mass cytometry (IMC) is a state-of-the-art technology which enables in situ analysis of complex cell populations in the tumor microenvironment (TME) in a single tissue section. We are now applying IMC for characterization of cell components in the tumor microenvironment in different stages of CTCL.

JAK inhibitors in cutaneous T cell lymphoma (CTCL)

Another research project is implementing clinical trial(s) for JAK inhibitors in CTCL. Constitutive activation of the Janus/ signal transducer and activator of transcription (JAK/STAT) pathway is implicated in the pathogenesis of CTCL. The JAK3 mutation was reported in a small portion of CTCL patients. Our recent study identified a new JAK3-INSL3 fusion transcript which may contribute to JAK3 over-activation (Cells, 12(19):2381, 2023). Thus, targeting JAK/STAT signaling pathway may be a promising therapeutic strategy for treating CTCL patients.