Li Yang, Ph.D.

Senior Investigator

Laboratory of Cancer Biology and Genetics

NCI/CCR

Building 37, Room 3134C
Bethesda,, MD 20892-4255

240-760-6809

yangl3@mail.nih.gov

Research Topics

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.

Biography

Dr. Li Yang is a Senior Investigator at the National Cancer Institute. 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 and was tenured in 2016. 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. 

Selected Publications

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Yang L, Karin M. Roles of tumor suppressors in regulating tumor-associated inflammation. Cell Death Differ. 2014;21(11):1677-86.


This page was last updated on September 12th, 2019