Research Projects

Monoclonal antibody therapy of lymphoid malignancies is dependent on effective macrophage phagocytosis

The addition of anti-CD20 monoclonal antibody (mAb) to treatments of CLL was the first significant improvement in patient outcomes. The major mechanism of removal of anti-CD20 coated CLL cells is via antibody-dependent cell phagocytosis by macrophages. Patient CLL cells eventually develop resistance to anti-CD20 mAb therapy. Our laboratory is interested in understanding the basis for mAb therapy resistance.

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Lymphoid malignancies characterization by large-scale multiparameter and high-dimensional modality analyses may uncover new cell subpopulation correlations with disease

Lymphoid malignancies are cancers of the immune system whose behaviors are highly dependent on the associated non-cancerous cells that help the cancer grow in its local environment. We are analyzing large-scale multiparameter data on paired blood and lymphoid malignancy specimens with the SWIFT (Scalable Weighted Iterative Flow-clustering Technique) algorithm to characterize unique cell subpopulations within the lymphoid malignancy local environment.

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Xenograft mouse models of lymphoid malignancies as a basis for understanding tumor microenvironment

Lymphoid malignancies are cancers of immune cells that now grow out of control. Paradoxically, these isolated cancer cells do not grow well in the laboratory. We propose to utilize lymphoid malignancy xenograft models to define and study the critical microenvironment cells and factors required to grow these cancer cells in the laboratory.

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Role of AID/APOBEC mutagenesis in evolution of aggressive lymphoid malignancies

In lymphoid malignancies, new mutations acquired by the malignant cancer cell often correlate with aggressive disease and worse patient outcome. The mechanism for generating new mutations in these cancers is not clear. Research by our lab and others has suggested that abnormal activity of activation-induced deaminase (AID) and other APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide) family of cytidine deaminases may be involved.

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Recognition of specific apoptotic cells by CLL antibody is critical for maintenance and evolution of CLL clone

My laboratory has been defining the molecule(s) that bind to the antibodies made by CLL cells. We have shown that antibodies from one subset of CLL patients, whose cells express an unmutated antibody characterized by a heavy (H) chain encoded by IGHV1-69, IGHD3-16, and IGHJ3 and a light (L) chain encoded by IGKV3-20, bind an intracellular protein, non-muscle myosin heavy chain IIA (myosin). We have further shown that a subset of dying cells, myosin exposed apoptotic cells (MEACs), are recognized by CLL antibodies. CLL antibody binding to MEACs correlated with poor patient survival, implying that apoptotic cells may drives CLL to proliferate and evolve towards aggressive disease.

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