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

Metastatic spread accounts for most cancer-associated deaths in patients, but treatment options are limited. How cancer cells acquire the competence to colonize distant organs is poorly understood. The goal of my research team is to identify the cause-effect mediators that link the genomic/epigenetic alterations and tumor microenvironment and options for therapeutic intervention. We collaborate with basic research laboratories as well as clinicians and epidemiologists.

We have several focused research areas:

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. It is not clear whether TSs play a direct role in metastatic colonization. Our studies demonstrate that tumor suppressors are often silenced during metastatic progression through epigenetic mechanisms (e.g., promoter hypermethylation and histone modification). TS deregulation promotes the acquisition of plasticity and the ability of tumor cells to adapt to hostile tissue microenvironments, thus facilitating metastatic spread. We use integrated genome-wide genetic and epigenetic approaches to investigate the role of TSs during metastatic progression and the underlying mechanisms involving host inflammatory and immune responses.

Epithelial and myeloid TGF-β in cancer metastasis: TGF-β is a powerful metastasis promoter in 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 and microenvironment, including host myeloid cells or stromal fibroblasts, to discover molecular mediators and pathways important in tumor-stroma crosstalk.

Immune microenvironment regulation of tumor dormancy: the ability of residual tumor cells to persist in a dormant state can occur during metastatic progression and/or following extended periods of clinical remission that may last decades. The mechanisms for tumor dormancy induction or tumor cell reactivation remain unclear. We are currently using in vitro and in vivo molecular imaging, single-cell RNA sequencing, and mouse models of breast cancer to investigate the molecular and cellular mechanisms mediated by the immune microenvironment in tumor dormancy.

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, and others as well.

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. 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

This page was last updated on Thursday, June 23, 2022