Our Science – Yang Website
Li Yang, Ph.D.
Tumor metastases account for the majority of cancer associated deaths in patients. There are very few effective treatment options. Evidence from recent years strongly suggests that the tumor-stroma interactions are indispensable participants in the metastatic process. Our research program uses TGF-β as a molecular model to study the mechanisms underlying this tumor-stroma interaction. In addition, we identify molecular mediators in inflammatory tumor microenvironment that are important for metastatic colony formation. Our work will provide molecular insight to the 'seed and soil' hypothesis in cancer metastasis and to develop new treatment options.
Identification of metastasis-promoting mediator of TGF-β: TGF-β is a powerful metastasis promoter in the later stages of cancer progression, however it mediates growth inhibition in early stages. The factors mediating the functional change of TGF-β are largely unknown, which poses significant challenges to our understanding of TGF-β cancer biology and to the successful application of TGF-β targeted therapy. We utilize focused genetic models in which TGF-β signaling is inactivated in specific cell types in the tumor microenvironment such as tumor cells, host myeloid cells, or stromal fibroblasts to discover molecular mediators and pathways important in tumor-stroma cross-talk. We use comprehensive gene and protein profiling technology, as well as a number of mouse models for identification and functional validation. We are currently working on the effect and molecular mechanisms of myeloid specific TGF-β signaling on tumor metastasis.
Premetastatic environment in distant organ: Many tumors demonstrate a metastatic predisposition to specific organs. This is believed to be influenced by inherent molecular differences in tumor cell themselves and their interaction with host factors, namely the “seed and soil”. Our ongoing studies suggest that inflammatory myeloid cells actively contribute to the establishment of metastasis colonies in distant organ. Our laboratory uses a number of in vitro and in vivo model system to dissect cellular and molecular mechanisms underlying this process. We also utilize advanced ex vivo imaging technologies to analyze the molecular and cellular events at real time during early metastatic colony formation.
Inflammation, tumor progression and metastasis: Alteration or down regulation of TGF-β signaling is frequent in many cancer types. We have previously shown that deletion or down-regulation of TGF-β signaling in tumor cells induces inflammation and immune cell recruitment in the tumor microenvironment (Yang et al., 2008, Cancer Cell 13, 23-35). However, the molecular mechanisms for the effect of inflammation on epithelial compartment remain to be investigated. We are investigating genetic and epigenetic alterations in the epithelial compartment through inflammation-mediated mechanisms. We use integrated genomic-wide genetic and epigenetic technology to discover key mediators.
In summary, our research program investigates the molecular mechanisms underlying tumor-stroma interaction in the metastatic process. Our research approaches include cellular and molecular biology, cancer biology, immunology, biochemistry, as well as integrated genomic-wide genetic, epigenetic, and proteomic technology. We collaborate with several basic research laboratories as well as clinicians and epidemiologists for translational studies.
Please contact Dr Li Yang at email@example.com for information regarding the availability of post-doctoral and graduate fellowship positions in the lab. Graduate students may apply through the Graduate Partnership Program (firstname.lastname@example.org) that sponsors doctoral students at NIH through partnerships with various Universities, including University of Maryland and Johns Hopkins.
This page was last updated on 11/26/2013.