Molecular Pathogenesis of Hematological Malignancies
Dr. Y. Lynn Wang serves as the Director of the Molecular Hematopathology Laboratory at Weill Cornell. This CLIA-certified and CAP-accredited clinical laboratory offers PCR-based testing for molecular genetic lesions in lymphomas and leukemias to aid in the diagnosis and therapeutic monitoring. Research in her clinical laboratory focuses on new molecular test development (Diag Mol Path. 14,17-22, 2005; J. Mol. Diagn. 8, 231-9, 2006; J. Mol. Diagn. 8, 385-9, 2006; J. Mol. Diagn. 9, 272-6, 2007). The lab, in collaboration with hematologists/oncologists, also performs research that helps define and explore the clinical utilities of these new tests (Acta Haematol. 118, 209-14, 2007; Leukemia. 22, 1289, 2008). In addition, Dr. Wang is an active member of the International BCR-ABL RQ-PCR Standardization Group that conducts research and makes recommendations for clinical laboratory practice (Blood, 108, 28-37, 2006; Blood, 112, 3330-8, 2008 and Blood 2010 in print).
Besides clinical service and clinical laboratory research, Dr. Wang acts as the principal investigator of a translational research laboratory. The lab focuses on aberrant signal transduction in lymphomas and leukemias as well as utilization of derived information to develop molecularly targeted therapies. A variety of molecular, cellular, immunological, biochemical and pharmacological approaches are utilized to determine the contribution of particular signaling cascades in the pathogenesis of these hematological malignancies (J. Immunol. 177, 3737-45, 2006; Am. J. Pathol. 170, 722-32, 2007; PPAR Research, v2008, 1-13, 2008; Leukemia. 22, 1755-66, 2008). Currently, a number of projects aim to understand the role of B-cell receptor (BCR) signaling in lymphoma cell survival and proliferation. Several papers from the lab showed that dasatinib, a SRC tyrosine kinase inhibitor, interferes with BCR signaling and causes cell cycle arrest or apoptosis in diffuse large B cell lymphoma (DLBCL) and CLL. The data not only suggests dasatinib as a potentially useful therapy for these lymphomas but also demonstrates the critical role of BCR signaling in lymphoma cell proliferation and survival. Moreover, potential biomarkers have been identified by these studies to predict dasatinib therapeutic response (Leukemia 22, 1755-66, 2008, Leukemia 23, 807-10, 2009, Clin. Cancer Res., 16, 587-99, 2010 ). Based on some of these promising preclinical data, a phase II clinical trial that integrates the identified biomarkers has been initiated and openned in June 2009 to test the efficacy of dasatinib in lymphoma patients. Since the establishment of her research lab in 2005, work from the Wang lab has led to 22 publications in the scientific literature. Many of the projects were initiated and conducted in their own lab and still many other involve collaborations with other scientists, pathologists and heme/onc physicians at Weill Cornell, other institutions and industrial companies.