Research

We study how immune cells maintain activity against myeloma and how myeloid cells sustain inflammation in secondary hemophagocytic lymphohistiocytosis (HLH) and related syndromes. We use patient samples to identify immune cell states, then test their functions experimentally.

Immune surveillance in plasma cell disorders

Which immune cells retain the ability to recognize and kill myeloma cells, and how can their activity be strengthened?

Our work has identified several mechanisms of immune surveillance in myeloma. Adaptive natural killer (NK) cells express less CD38 and resist daratumumab-induced fratricide; their abundance in bone marrow is associated with antibody-dependent cytotoxicity. Tumor-derived soluble MIC reduces NKG2D expression and NK-cell function, which an anti-MIC antibody restores ex vivo. Clonally expanded CD4 cytotoxic T cells also kill myeloma cells through NKG2D, and their abundance is associated with survival.

We are now studying when these immune cell states emerge as monoclonal gammopathy of undetermined significance progresses, and whether they could help identify patients for T-cell-redirecting therapy.

Key publications. Clinical Cancer Research 2021 · Journal for ImmunoTherapy of Cancer 2024 · Blood 2025

Myeloid cell states in hyperinflammation

What sustains inflammation in secondary HLH and immune effector cell-associated syndromes, and when does it begin?

Diagnosis relies on a combination of clinical and laboratory findings. The model developed largely from familial HLH links uncontrolled CD8 T-cell activation to interferon-gamma-driven macrophage activation. This model explains adult malignancy-associated HLH less well, as cytotoxic function is often intact.

We study how myeloid progenitors respond to emergency myelopoiesis and when they acquire an inflammatory program. Using paired bone marrow and blood samples from patients with secondary HLH, we combine single-cell transcriptomics, chromatin accessibility analysis, plasma proteomics, and functional experiments.

From patient samples to clinical studies

We maintain a longitudinal biobank linked to clinical data and conduct correlative studies alongside investigator-initiated trials in relapsed and refractory disease. In our study of multiple myeloma, measurable residual disease (MRD) negativity measured by next-generation sequencing (NGS) was associated with longer progression-free and overall survival. Fragment analysis did not predict survival. The adverse prognosis associated with high-risk cytogenetics was also reduced in patients who achieved NGS-based MRD negativity.

Key publication. British Journal of Haematology 2022

Techniques

Single-cell profiling
Single-cell RNA and TCR sequencing; single-nucleus RNA–ATAC multiome

Functional immunology
High-parameter spectral flow cytometry; primary patient-cell assays; in vivo models

Clinical translation
Longitudinal biobanking; plasma proteomics; correlative studies alongside investigator-initiated trials