Our work focuses on understanding blood development to discover and design novel therapies for cancer, using mass spectrometry to identify non-genetic determinants underlying functional differences in stem and progenitor cell states and fates. Our research couples this discovery platform with faithful disease model systems to answer fundamental biological questions about how cancer develops and how to treat it. We collaborate with many other labs at City of Hope and across the country in four main areas: 1) small-scale mass spectrometry platform development; 2) chimeric antigen receptor (CAR) T cell therapy for brain tumors; 3) the role of ARHGAP25 in hematopoeisis; and 4) acute myeloid leukemia (AML) stem cells.
Small scale proteomic discovery of activated pathways in blood cells. We work to develop and improve high-resolution proteomic and phosphoproteomic discovery platforms capable of identifying thousands of proteins from hundreds of thousands of cells. We use these platforms to identify protein pathways important for survival, function, and persistence of leukemia stem cells (LSCs) and CAR T cells. Our proteomics efforts are a collaboration with Dr. Markus Kalkum’s group at City of Hope.
Mass spectrometry-based profiling of tumor-responsive immune cells. City of Hope is a world leader in immuno-oncology, and at the forefront of the chimeric antigen receptor (CAR) T cell revolution. Although this powerful new therapy has had some remarkable successes, its use in solid tumors is limited by several factors, including a failure of CAR T cells to persist in situ. In collaboration with Dr. Christine Brown, our lab is working to identify a proteomic signature of CAR T cell persistence in xenotransplantation models of pediatric brain tumors. This will permit improved engineering of these cells for solid tumor immunotherapy.
Proteomic interrogation of human leukemia stem cells. In collaboration with Dr. Guido Marcucci, we are defining the phosphoproteomic features of adult and pediatric leukemia stem cells (below). This will make possible the proteomic profiling of individual patient samples, permitting the generation of unique patient-specific phosphoproteomic fingerprints and realizing the potential of precision medicine on a proteomic level.
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Wang LD, Ficarro SB, Hutchinson JN, Csepanyi-Komi R, Nguyen PT, Wisniewski E, Sullivan J, Hofmann O, Ligeti E, Marto JA, Wagers AJ.
Blood. 2016; 128(11):1465-74.
Rowe RG, Wang LD, Coma S, Han A, Mathieu R, Pearson DS, Ross S, Sousa P, Nguyen PT, Rodriguez A, Wagers AJ, Daley GQ.
The Journal of experimental medicine. 2016; 213(8):1497-512.
Wang LD, Rao TN, Rowe RG, Nguyen PT, Sullivan JL, Pearson DS, Doulatov S, Wu L, Lindsley RC, Zhu H, DeAngelo DJ, Daley GQ, Wagers AJ.
Leukemia. 2015; 29(6):1320-30. NIHMSID: NIHMS662665
- Overlapping roles for endothelial selectins in murine hematopoietic stem/progenitor cell homing to bone marrow.
Nabors LK, Wang LD, Wagers AJ, Kansas GS.
Experimental hematology. 2013; 41(7):588-96. NIHMSID: NIHMS475023
Wang LD, Wagers AJ.
Nature reviews. Molecular cell biology. 2011; 12(10):643-55. NIHMSID: NIHMS571834