Li Yang, Ph.D.
Dr. Yang’s research program focuses on molecular mechanisms underlying tumor-stroma interaction in cancer metastasis. Her studies demonstrate that cancer-associated inflammation is critical in the functional switch of TGF-β from a suppressor to a promoter. Her team is currently investigating how myeloid-specific TGF-β signaling modulates host inflammation/immune response in cancer and other pathological conditions.
As head of the Tumor Microenvironment Section, Dr. Yang is particularly interested in how inflammation in the premetastatic environment modifies cancer cell colonization. Her research approaches include cellular and molecular biology, cancer biology, immunology, as well as integrated genomic-wide genetic and epigenetic approaches.
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.
Selected Key Publications
MicroRNAs 130a and 145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved anti-tumor immunity.Nature Communications. in press, 2018. [ Journal Article ]
Attenuation of Myeloid-Specific TGFβ Signaling Induces Inflammatory Cerebrovascular Disease and Stroke.Circulation Research. 121: 1360-1369, 2017. [ Journal Article ]
- Cancer Discovery. 3: 936-51, 2013. [ Journal Article ]
Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling.PLoS Genetics. 9: e1003251, 2013. [ Journal Article ]
Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis.Cancer Cell. 13: 23-35, 2008. [ Journal Article ]
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.
|J. Megan Chen||Postbaccalaureate Fellow|
|Christine M. Hollander Ph.D.||Senior Research Assistant|
|Hiroki Ishii Ph.D.||Postdoctoral Fellow (Visiting)|
|Alisa Malyavko||Special Volunteer|
|Woo Yong Park Ph.D.||Postdoctoral Fellow (Visiting)|
|Jae Young So Ph.D.||Research Fellow|
|Xiang Wang Ph.D.||Postdoctoral Fellow (Visiting)|
|Zhiguang Xiao Ph.D.||Postdoctoral Fellow (Visiting)|
|Sara Zahraeifard Ph.D.||Postdoctoral Fellow (CRTA)|
Li Yang and her cancer research team have reported that experiments with mice suggest inflammation alone can lead to stroke. Learn more...