The Chang lab has pioneered discoveries of long noncoding RNAs (lncRNAs) as a pervasive and important class of regulators in human diseases, notably in cancer. LncRNAs can serve as the interface between DNA and chromatin modification machinery, and thus mediate epigenetic aberrations in cancer. The lncRNA HOTAIR is overexpressed in approximately a third of human breast carcinomas and is a powerful predictor of eventual metastasis and death. The long term goal of this program is to understand the mechanistic basis of lncRNA action in human cancers. Our investigations will address (i) the roles of lncRNAs in driving cell-to-to cell epigenetic heterogeneity, a critical issue in cancer metastasis and therapy resistance, using cutting edge single cell epigenomic technology and in vivo genetic models; (ii) the emerging roles of RNA chemical modifications in cancer development; (iii) noncoding mutations that change RNA structure (?ribosnitches?) and use new epigenome editing technologies to pinpoint driver lncRNA genes in human cancers. These experiments will provide key insights into how long noncoding RNAs may instigate cancer progression, and should pave the way for new cancer diagnostics and treatments in the future.

Public Health Relevance

Cancer deaths are most often caused by the spread of cancer to other sites of the body. A new type of genes, termed long noncoding RNA (lncRNA), has been found to be important to control cancer metastasis-- especially in breast cancer, the second most common cause of cancer death for women. Research into how lncRNAs control gene activities in breast cancer will help to improve the risk assessment of cancer patients and identify targets for cancer therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA209919-02
Application #
9325477
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Mietz, Judy
Project Start
2016-08-03
Project End
2023-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Stanford University
Department
Dermatology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
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Cho, Seung Woo; Xu, Jin; Sun, Ruping et al. (2018) Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element. Cell 173:1398-1412.e22
Schmitt, Adam M; Chang, Howard Y (2017) Long Noncoding RNAs: At the Intersection of Cancer and Chromatin Biology. Cold Spring Harb Perspect Med 7:
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Corces, M Ryan; Chang, Howard Y; Majeti, Ravindra (2017) Preleukemic Hematopoietic Stem Cells in Human Acute Myeloid Leukemia. Front Oncol 7:263