Our laboratory studies cancer stem cells with the ultimate goal of developing novel therapies. In 2004, we initially isolated and characterized cancer stem cells in the plasma cell malignancy multiple myeloma. Since that time we have utilized the techniques we developed to similarly identify cancer stem cells in pancreatic cancer and Hodgkin’s disease. Using these tumor systems as models we have found that cancer stem cells are relatively resistant to standard chemotherapeutic agents, are regulated by cellular pathways that dictate cell fate decisions during embryonic development (e.g., Sonic Hedgehog and Notch), and play a major role in disease progression and metastases. We have also developed several novel therapies targeting cancer stem cells and have translated these into clinical trials that are currently enrolling patients in the Johns Hopkins Oncology Center. Lastly, we have begun to study whether the pathways we have identified in cancer stem cells are also important for regulating normal stem cells and examine their functions in normal hematopoiesis using transgenic mouse models.
Matsui, W, Huff, CA, Wang, Q, Malehorn, MT, Barber, J, Tanhehco, Y, Smith, BD, Civin, CI, Jones, RJ. Characterization of clonogenic multiple myeloma cells. Blood. 2004; 103:2332-2336.
Peacock, CD, Wang, Q, Gessell, GS, Corcoran-Scwartz, IM, Jones, E, Kim, J, Devereux, WL, Rhodes, JT, Huff, CA, Beachy, PA, Watkins, DN, Matsui, W. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proceedings of the National Academy of Science. 2007; 104: 4048-4053.
Matsui W, Wang Q, Barber J, Brennan S, Smith B, Borrello I, McNiece I, Lin L, Ambinder R, Peacock C, Watkins N, Huff C, Jones R. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Research. 2008; 68:190-197.
Huff CA and Matsui W. Multiple Myeloma Cancer Stem Cells. Journal of Clinical Oncology. 28: 2895-2900, 2008.
Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, Koorstra JB, Rajeshkumar NV, He X, Goggins M, Iacobuzio-Donahue, Berman DM, Laheru D, Jimeno A, Hidalgo M, Maitra A, Matsui W. Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. Journal of the National Cancer Institute. 2010; 102: 340-351.
Jones RJ, Gocke CD, Kasamon YL, Miller CB, Perkins B, Barber JP, Vala MS, Gerber JM, Gellert LL, Siedner M, Lemas MV, Brennan S, Ambinder RF, Matsui W. Circulating clonotypic B cells in classical Hodgkin’s lymphoma. Blood. 2009; 113:5920-5926.
Merchant A, Joseph G, Wang Q, Brennan S, Matsui W. Gli1 regulates the proliferation and differentiation of HSC and myeloid progenitors. Blood. 2010; 115:2391-2396.
Ishizawa K, Rasheed ZA, Karisch R, Wang Q, Kowalski J, Susky E, Pereira K, Karamboulas C, Moghal N, Rajeshkumar NV, Hidalgo M, Tsao M, Ailles L, Waddell T, Maitra A, Neel BG, Matsui W. Tumor-initiating cells are rare in many human tumors. Cell Stem Cell. 2010; 7:279-282