Dr. Y. Lynn Wang is an accomplished molecular biologist and Board certified Clinical Pathologist. She is the Director of the Molecular Hematopathology Laboratory and her laboratory offers molecular testing services including: Lymphoma tests, Leukemia tests and Lymphoma associated virus detection. Dr. Wang also directs an NIH funded research laboratory working on role of PPAR gamma in lymphocyte survival and lymphomagenesis.
Dr. Wangs research interest is focused on the molecular mechanisms underlying the pathogenesis of lymphomas. We are interested in the molecules that affect lymphocyte survival or apoptosis since failure of cells to die plays an important role in the pathogenesis of lymphocytic neoplasms such as follicular lymphomas and chronic lymphocytic leukemias.
One of the molecules we identified is PPAR gamma (PPARg). PPARg is a nuclear hormone receptor/transcriptional factor that requires ligand binding for activation. The molecule is most abundantly expressed in adipose tissue. Studies of PPARg have thus far been focused on adipose tissue. PPARg also is expressed in B and T cells. However, little is known about its primary functions in the immune system. Using high concentrations of PPARg pharmacological ligands, glitazones, some recent studies have found that the drugs induce apoptosis in normal or malignant lymphocytes, suggesting that PPARg down regulates immune functions and PPARg ligands may be useful for treating lymphomas.
In contrast to these studies, we have discovered that using low concentrations of glitazones, that are comparable to their Kd for PPARg, activation of the hormone receptor protected cells from apoptosis induced by growth factor withdrawal. We have shown that the survival enhancing effects depended on both the presence and activation of PPARg. Mechanistic studies revealed that PPARg promotes cell survival by enhancing the ability of cells to maintain their mitochondrial membrane potential (J. Biol. Chem., 277, 31781-8, 2002). These results led us to believe that PPARg, when activated, promotes cell survival rather than inducing cell death. The apoptotic effect observed previously is likely a result of the non-specific toxicity of glitazones at high concentrations. More recently, we have shown that PPARg is over expressed in several cell lines established from a subset of human lymphomas and the over expression contributes to increased survival of these tumor cells. Taken together, our data have demonstrated for the first time that activation of PPARg can promote cell survival and suggest that PPARg antagonists as opposed to agonists have the potential to serve as antitumor agents. Currently, we are in the process of studying the mechanisms that underlie the cell survival-promoting effects of PPARg.
The other projects in the laboratory focus on identification of novel molecules involved in the pathogenesis of human diffuse large B cell lymphomas (DLBCL). This type of lymphoma represents the most common and the least characterized non-Hodgkins lymphomas. USing human tumor tissues, we first identify those molecules that have the potential to serve as diagnostic or sub-classification markers. We then delineated the functions of these molecules in cell survival, proliferation and differentiation. Cutting-edge technologies such as DNA microarray, laser capture microdissection, real-time PCR and RNAi are employed for these studies.
Y. Lynn Wang, MD, PhD, is an associate professor and an associate attending pathologist at Weill Cornell Medical College and New York-Presbyterian Hospital in New York City, United States. She is also a member of Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center. Dr. Wang serves as the Director of Molecular Hematopathology Laboratory at Weill Cornell that provides eleven molecular tests to the Heme/Onc physicians and hematopathologists. Additionally, Dr. Wang directs a basic research laboratory working on aberrant signal transduction pathways in lymphoma and leukemia. Her research aims at understanding molecular pathogenesis of hematologic malignancies and utilizing such information for diagnosis, disease monitoring, therapeutic intervention and therapeutic response prediction. Her group has been actively publishing in these areas (See Publications).
Dr. Wang has been involved in a number of extramural scholastic activities. She is an elected officer of the Association for Molecular Pathology. She is a member of the International BCR-ABL qPCR standardization group contributing experimental evidence leading to clinical practice recommendations. She is also a participant in the Molecular Oncology Reference Materials project (GeT-RM project) sponsored by Centers for Disease Control and Prevention. She reviews manuscripts for several professional journals
Dr. Wang received her MD from Beijing Medical University in China (conferred to a US MD degree in 2002) and her PhD from Brandeis University. She conducted her Clinical Pathology Residency, Clinical Molecular Pathology Fellowship and postdoctoral research at the University of Pennsylvania. She is board-certified in Clinical Pathology and Molecular Genetic Pathology. Dr. Wang is a member of Association for Molecular Pathology, American Society of Hematology, College of American Pathologists, and American Society for Investigative Pathology.
