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. How cancer cells acquire the competence to colonize distant organs is poorly understood. Evidence from recent years strongly suggests that the tumor-stroma interactions are indispensable participants in the metastatic process. The goal of my research team is to identify the cause-effect tumor microenvironment mediators for metastasis progression and options for therapeutic intervention. We have several focused research areas:
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 are currently working on the effect and molecular mechanisms of myeloid-specific TGF-β signaling on tumor metastasis.
Roles of tumor suppressors (TSs) in metastatic progression: TSs are powerful transcriptional and signaling regulators that negatively modulate cell proliferation and survival. As such, TSs counteract the growth promoting activity of oncogenes mainly through cell autonomous mechanisms. TSs are frequently inactivated in sporadic cancers through biallellic inactivation, or a single allele mutation. In addition, promoter hypermethylation is one of the most consistent epigenetic mechanisms in silencing tumor suppressors in human cancers. We are currently investigated whether TSs play critical roles in cancer metastasis, and if so, what are the underlying cellular and molecular mechanisms.
Inflammation and epigenetic reprogramming: Epigenetic alterations including DNA methylation and histone modifications through mechanisms of an abnormal cellular memory are important mechanisms for cancer cells to acquire key traits of full malignancy. We are investigating epigenetic alterations in the metastatic cancer cells mediated by the inflammatory tumor microenvironment. 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, 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.
|Carla Gibbs||Predoctoral Fellow (Graduate Student)|
|Justin Gray||Predoctoral Fellow (Graduate Student)|
|Christine M. Hollander Ph.D.||Senior Research Assistant|
|Alexander Kwarteng Ph.D.||Postdoctoral Fellow (Visiting)|
|Feng Leng Ph.D.||Scientist (Contr.)|
|Woo Yong Park Ph.D.||Postdoctoral Fellow (Visiting)|
|Jae Young So Ph.D.||Research Fellow|
|E.V. Trinadharao Sornapudi 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...