Quantitative Translation of the Cancer Genome to Proteome

Preclinical Evaluation and Development of New Therapeutic Strategies in Multiple Myeloma

Multiple myeloma, a malignancy of plasma cells, is the second most common hematoligic malignancy in the United States and currently has no known cure. While the development of new therapeutics over the past decade has significantly extended lifespan in this disease, there is still significant work left to do for patients. The Multiple Myeloma Translational Initiative Laboratory, within our group, uses a number of in vitro and in vivo models of myeloma to evaluate the efficacy of promising new therapeutic strategies in myeloma. We also aim to use basic science and screening strategies to identify new drug targets and diagnostic approaches toward this disease.

Currently, we are particularly focused on four major avenues of targeting myeloma: 1) via new ways to target protein homeostasis (see Le Moigne, Aftab et al Mol Cancer Therap 2017, among others); 2) by evaluating the potential role of targeting the splicing machinery in combination with proteasome inhibition (see Huang et al, ASH abstract 2017); 3) aberrant signaling driven by kinases in interaction with the bone marrow microenvironment (see Lam et al, Biorxiv 2017); 4) manipulating and enforcing antigen expression at the plasma cell surface to enhance myeloma immunotherapy (unpublished).

Notably, in all these endeavours, we take advantage of our expertise in quantitative enrichment-based proteomics as well as collaborations with UCSF-based world leaders in chemical biology, immunology, cellular engineering, and functional genomics, to further the scope of our investigations. We also have active collaborations underway with industry partners to develop new small molecule and immunotherapy strategies for this disease. In addition, we are also actively developing a new patient-derived xenograft model of myeloma, a major need in the field.