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Li  Yang, Ph.D.

Li Yang, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

Dr. Yang’s research program focuses on the mechanisms underlying tumor-host interplay in cancer metastatic progression. Dr. Yang has contributed to the identification of the immune and inflammatory mediators in the anti- and pro-tumor functional switch of TGF-β, the epigenetic regulation of TGF-β signaling, mechanisms of myeloid cell recruitment in the tumor microenvironment, as well as myeloid TGF-β signaling in cancer immune surveillance and in inflammatory stroke.

As the head of the Tumor Microenvironment and Metastasis Section, Dr. Yang is particularly interested in how tumor suppressors modulate the host immune environment, and the epigenetic mechanisms responsible for tumor cell plasticity and metastatic colonization.

Areas of Expertise

Tumor Suppressors, TGF-β, Inflammatory and Immune Response
Myeloid Cells

Publications

Selected Key Publications

Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway

Park W-Y, Gray JM, Holewinski RJ, Andresson T, So JY, Carmona-Rivera C, Hollander MC, Yang HH, Lee M, Kaplan MJ, Cappell SD, Yang L.
Nature Cancer. 4(3): 419-435, 2023.
Full-Text Article
[ Journal Article ]

Induction of DNMT3B by PGE2 and IL6 at Distant Metastatic Sites Promotes Epigenetic Modification and Breast Cancer Colonization

So JY, Skrypek N, Yang HH, Merchant AS, Nelson GW, Chen WD, Ishii H, Chen JM, Hu G, Achyut BR, Yoon EC, Han L, Huang C, Cam MC, Zhao K, Lee MP, Yang L.
Cancer Res. 80(12): 2612-2627, 2020. [ Journal Article ]

miR-130a and miR-145 reprogram Gr-1+CD11b+ myeloid cells and inhibit tumor metastasis through improved host immunity

Ishii H, Vodnala SK, Achyut BR, So JY, Hollander MC, Greten TF, Lal A, Yang L.
Nat Commun. 9(1): 2611, 2018. [ Journal Article ]

TGF-β signaling in myeloid cells is required for tumor metastasis

Pang Y, Gara SK, Achyut BR, Li Z, Yan HH, Day CP, Weiss JM, Trinchieri G, Morris JC, Yang L.
Cancer Discov. 3(8): 936-51, 2013. [ Journal Article ]

Roles of tumor suppressors in regulating tumor-associated inflammation

Yang L, Karin M
Cell Death and Differentiation. 21: 1677-1686, 2014.
Full-Text Article
[ Journal Article ]

Job Vacancies

We have no open positions in our group at this time, please check back later.

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Team

Celine Kieu photo
Postdoctoral Fellow
Celine Kieu, Ph.D.
Henry Yang Gu photo
Postdoctoral Fellow (Visiting)
Henry Yang Gu, Ph.D.
Tiffany Andohkow photo
Postbaccalaureate Fellow
Tiffany Andohkow
Rachel Yang photo
Postbaccalaureate Fellow
Rachel Yang
Carter Sellner photo
Postbaccalaureate Fellow
Carter Sellner

News


Justin Gray was featured in an NIH SciBites video:

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Screen shot of Justin Gray SciBites video

"How Dying Cancer Cells Fuel Tumor Growth"


Justin Gray, a graduate student in the NIH-Johns Hopkins GPP, awarded his Ph.D.

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Justin Gray photo

Justin completed his doctoral research in the Yang lab (July 2017 - June 2022) and is now working at BioNTech.

Covers

Nature Cancer cover for Park et al. 2023

Apoptosis-induced nuclear expulsion in tumor cells drives S100A4-mediated metastatic outgrowth

Published Date

Most tumor cells undergo apoptosis in circulation and at the metastatic organ sites due to host immune surveillance and a hostile microenvironment. It remains to be elucidated whether dying tumor cells have a direct effect on live tumor cells during the metastatic process and what the underlying mechanisms are. Here we report that apoptotic cancer cells enhance the metastatic outgrowth of surviving cells through Padi4-mediated nuclear expulsion. Tumor cell nuclear expulsion results in an extracellular DNA–protein complex that is enriched with receptor for advanced glycation endproducts (RAGE) ligands. The chromatin-bound RAGE ligand S100a4 activates RAGE receptors in neighboring surviving tumor cells, leading to Erk activation. In addition, we identified nuclear expulsion products in human patients with breast, bladder and lung cancer and a nuclear expulsion signature correlated with poor prognosis. Collectively, our study demonstrates how apoptotic cell death can enhance the metastatic outgrowth of neighboring live tumor cells.

This article was also highlighted in the Editorial section of Nature Cancer.

Citation
Park W-Y, Gray JM, Holewinski RJ, Andresson T, So JY, Carmona-Rivera C, Hollander MC, Yang HH, Lee M, Kaplan MJ, Cappell SD, Yang L. 2023. Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway. Nature Cancer 4:419–435. doi:10.1038/s43018-023-00524-z
Molecular Cancer Research cover image for So et al. 2022

DNA Methyltransferase 3B–Mediated Intratumoral Heterogeneity and Therapeutic Targeting in Breast Cancer Recurrence and Metastasis

Published Date

The mechanisms of how cancer cells are selected and evolve to establish distant metastatic colonies remain unclear. Tumor heterogeneity and lack of biomarkers are some of the most difficult challenges in cancer biology and treatment. Here using mouse models for triple-negative breast cancer (TNBC) metastasis, we report heterogeneous expression of DNA methyltransferase 3B (DNMT3B) in both mouse and human primary tumors. High levels of DNMT3B were correlated with poor clinical outcomes in multiple human breast cancer datasets. Mechanistically, clonal cells with high DNMT3B (DNMT3BH) showed higher vimentin (VIM) expression and displayed enhanced epithelial-to-mesenchymal transition capacity. Deletion of VIM diminished the metastatic phenotype of DNMT3BH cells. Importantly, in preclinical mouse models in which the primary tumors were surgically removed, perioperative targeting of DNMT3B in combination with chemotherapy markedly suppressed tumor recurrence and metastasis. Our studies identify DNMT3B-mediated transcription regulation as an important mediator of tumor heterogeneity and show that DNMT3B is critical for tumor invasion and metastasis, reinforcing its potential as a target for treating metastatic disease.

 
Citation
So JY, Yang HH, Park WY, Skrypek N, Ishii H, Chen JM, Lee MP, Yang L. 2022. DNA methyltransferase 3B-mediated intra-tumoral heterogeneity and therapeutic targeting in breast cancer recurrence and metastasis. Mol Cancer Res MCR-21-0887. doi:10.1158/1541-7786.MCR-21-0887

TGF-β Signaling in Myeloid Cells Is Required for Tumor Metastasis

Published Date

This article was highlighted IN THE SPOTLIGHT of Cancer Discovery: Myeloid TGF-β Responsiveness Promotes Metastases

Citation
Pang Y, Gara SK, Achyut BR, Li Z, Yan HH, Day C-P, Weiss JM, Trinchieri G, Morris JC, Yang L. 2013. TGF-β Signaling in Myeloid Cells Is Required for Tumor Metastasis. Cancer Discovery 3:936–951. doi:10.1158/2159-8290.CD-12-0527

Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling

Published Date

This article was featured as a Research Highlight in Nature Reviews Cancer: Microenvironment: Making connections

Citation
Achyut BR, Bader DA, Robles AI, Wangsa D, Harris CC, Ried T, Yang L. 2013. Inflammation-Mediated Genetic and Epigenetic Alterations Drive Cancer Development in the Neighboring Epithelium upon Stromal Abrogation of TGF-β Signaling. PLOS Genetics 9:e1003251. doi:10.1371/journal.pgen.1003251