Research
We study plasma cell disorders from the single cell to the clinic, combining multiomic profiling of patient bone marrow with clinical trials in multiple myeloma and AL amyloidosis.
01
Plasma cell biology in AL amyloidosis
In AL amyloidosis, a small clone of plasma cells produces misfolded light chains that damage the heart, kidneys, and other organs. We use single-cell profiling of patient bone marrow to study the clonal plasma cells that drive the disease alongside the non-malignant plasma cells that surround them.
Key questions
- How do clonal plasma cells in AL amyloidosis differ from normal plasma cells and from myeloma cells?
- Which programs allow a small clone to produce large amounts of toxic light chain?
- How do polyclonal plasma cells and the immune system respond to the presence of the clone?
Approaches
- Single-cell RNA sequencing of bone marrow plasma cells
- Paired immune repertoire (BCR) profiling to separate clonal and polyclonal cells
- Integrative multiomic analysis
- Patient cohorts from the Boston Medical Center Amyloidosis Center
02
Bone marrow microenvironment and treatment response
Plasma cell disorders develop within the bone marrow, where immune, myeloid, and stromal cells shape how the disease grows and how it responds to therapy. We profile the marrow before and after treatment to understand which features of the microenvironment accompany deep and durable responses.
Key questions
- How do immune and myeloid compartments of the marrow change during therapy?
- Which features of the microenvironment before treatment are associated with response or resistance?
- How do stromal cells influence the behavior of malignant plasma cells?
Approaches
- Longitudinal single-cell profiling of paired bone marrow samples
- Chromatin accessibility profiling (ATAC-seq)
- Co-culture models of plasma cells and bone marrow stromal cells
- Computational analysis of cell–cell communication
03
Translational and clinical research in multiple myeloma
We design and lead clinical trials in multiple myeloma and related plasma cell disorders at Boston Medical Center, and we study biomarkers that can guide diagnosis, response assessment, and treatment choice for a diverse patient population.
Key questions
- Which biomarkers best capture depth of response, including minimal residual disease?
- How can genomic features of the tumor inform risk and treatment decisions?
- How do outcomes and access to novel therapies differ across patient populations, and how can trials reach underserved patients?
Approaches
- Investigator-initiated and cooperative clinical trials
- Genomic and transcriptomic profiling of patient samples
- Minimal residual disease assessment
- Outcomes research in diverse cohorts
04Future direction
Spatial organization of the bone marrow niche
Single-cell methods describe which cells are present in the marrow but not where they sit. We plan to map the spatial organization of plasma cells and their neighbors to understand how local niches support disease.
Key questions
- Where do clonal plasma cells reside in the marrow, and which cells are their neighbors?
- Do spatial niches differ across MGUS, AL amyloidosis, and multiple myeloma?
Approaches
- Spatial transcriptomics of bone marrow biopsies
- Multiplexed imaging
- Integration with single-cell reference atlases