Li Yang, Ph.D.
Laboratory of Cancer Biology and Genetics
Building 37, Room 3134C
Bethesda,, MD 20892-4255
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 the inflammatory tumor microenvironment that are important for metastatic colony formation. Our work will provide molecular insight into the "seed and soil" hypothesis in cancer metastasis and help 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 use 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 the tumor cells 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 systems to dissect the cellular and molecular mechanisms underlying this process. We also use advanced ex vivo imaging technologies to analyze the molecular and cellular events in 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 responsible for the effect of inflammation on the 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 for information regarding the availability of postdoctoral and graduate fellowship positions in the lab. Graduate students may apply through the Graduate Partnership Program that sponsors doctoral students at NIH through partnerships with various universities, including the University of Maryland and Johns Hopkins University.
Dr. Li Yang is a Senior Investigator at the National Cancer Institute (NCI). She received her Ph.D. in the Department of Cancer Biology at Vanderbilt University, under the mentorship of Dr. David Carbone. Her dissertation research focused on COX-2 pathway in tumor progression, immune suppression, and the contribution of host myeloid cells to tumor blood vessel formation. She investigated TGF-β regulation of inflammation and tumor microenvironment during her postdoc research with Dr. Harold Moses. She joined NCI in 2009. Her research program is devoted to understanding the molecular mechanisms underlying tumor-stroma interaction during metastatic process.
Dr. Yang is a recipient of the Federal Technology Transfer Award, co-recipient of FLEX Program Awards for Principal Investigators, CCR, NCI, as well as U.S.-China Biomedical Collaborative Research Grant award.
Yan HH, Jiang J, Pang Y, Achyut BR, Lizardo M, Liang X, Hunter K, Khanna C, Hollander C, Yang L. CCL9 Induced by TGFβ Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ. Cancer Res. 2015;75(24):5283-98.
Pang Y, Gara SK, Achyut BR, Li Z, Yan HH, Day CP, Weiss JM, Trinchieri G, Morris JC, Yang L. TGF-β signaling in myeloid cells is required for tumor metastasis. Cancer Discov. 2013;3(8):936-51.
Achyut BR, Bader DA, Robles AI, Wangsa D, Harris CC, Ried T, Yang L. Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling. PLoS Genet. 2013;9(2):e1003251.
Yang L, Pang Y, Moses HL. TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol. 2010;31(6):220-7.
Yang L, Karin M. Roles of tumor suppressors in regulating tumor-associated inflammation. Cell Death Differ. 2014;21(11):1677-86.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on June 15th, 2017