Yi Huang, MD, PhD
Assistant Professor of Pharmacology and Chemical Biology
The study of breast cancer epigenetics--meaning literally the various chromatin codes "above" the DNA sequencing --help us understand how tumorigenic factors alter gene expression within breast cancer cells. We now know that when we take active control of epigenetic defects, we can literally improve breast cancer prevention and control.
Yi Huang, MD, PhD
Research in Brief
Dr Huang’s research interests focus on the role of histone modification in breast cancer development. There is a growing body of evidence to suggest that changes in the activity of chromatin-modifying enzymes contribute to uncontrolled breast cell proliferation and tumorigenesis. Our main research objective is to define, in depth, the mechanisms and biological consequences of functional interplay between key histone enzymes in breast cancer growth and metastasis. We are also interested in identifying novel, small molecule reagents that act as selective inhibitors of important chromatin-modifying enzymes to target more specifically the small regions of chromatin and the subset of genes that are associated with most prominent alterations in the breast cancer genome. Our recent work indicated that activities of histone lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) are functionally linked in breast cancer, especially in triple negative breast cancer (TNBC). Clinically, TNBC is more aggressive, and distant visceral metastases are more common, in comparison with non-TNBC counterparts. TCGA data suggest that LSD1 is highly expressed in TNBC. We demonstrated that LSD1 inhibition in combination with HDAC inhibition displays superior synergy in blocking growth and inducing expression of aberrantly silenced genes in TNBC cells. We are investigating the precise mechanisms contributing to orchestrated crosstalk between histone modifiers in breast cancer and determining how the dysregulated interaction of histone-modifying enzymes leads to aberrant gene silencing and the aggressive phenotype of TNBC. We are also studying whether targeting crosstalk between epigenetic modulators and immune compartments could serve as a novel therapeutic approach for poorly immune responsive breast cancer patients. We have demonstrated that inhibition of LSD1 reactivates key immune checkpoint regulator and cytotoxic T cell-attracting chemokines, which in turn augments sensitivity of TNBC to immune checkpoint blocking antibody. These novel findings suggest that LSD1 inhibition may be an effective adjuvant treatment with immunotherapy as a novel management strategy for poorly immunogenic breast tumors.
- Qin Y, Vasilatos SN, Chen L, Wu H, Cao Z, Fu Y, Huang M, Vlad AM, Lu B, Oesterreich S, Davidson NE, Huang Y. Inhibition of histone lysine-specific demethylase 1 elicits breast tumor immunity and enhances antitumor efficacy of immune checkpoint blockade. Oncogene, Aug 15, 2018. PMID: 30111819
- Cao C, Wu H, Vasilatos SN, Chandran U, Qin Y, Wan Y, Oesterreich S, Davidson NE, Huang Y. HDAC5-LSD1 axis regulates antineoplastic effect of natural HDAC inhibitor sulforaphane in human breast cancer cells. Int. J. Cancer, 143: 1388-1401, 2018. PMID:29633255
- Cao C, Vasilatos SN, Bhargava R, Fine J, Oesterreich S, Davidson NE, Huang Y. Functional interaction of histone deacetylase 5 (HDAC5) and lysine-specific demethylase 1 (LSD1) promotes breast cancer progression. Oncogene, 36(1):133-145, 2017. PMID:27212032
- Katz TA, Vasilatos SV, Oesterreich S, Davidson, NE, Huang Y. Inhibition of histone
demethylase, LSD2 (KDM1B), attenuates DNA methylation and increases sensitivity to DNMT inhibitor-induced apoptosis in breast cancer cells. Breast Cancer Res. Treat.,
146(1):99-108, 2014. PMID: 24924415
- Vasilatos SV, Katz TA, Oesterreich S, Wan Y, Davidson, NE, Huang Y. Crosstalk between
Lysine-specific Demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells. Carcinogenesis, 34(6):1196-207, 2013. PMID: 23354309
- Zhu Q, Jin L, Casero RA, Davidson NE, Huang Y. Role of ornithine decarboxylase in regulation of estrogen receptor alpha expression and growth in human breast cancer cells. Breast Cancer Res. Treat., 136:57-66, 2012. PMID: 22976807
- Huang Y, Vasilatos S, Boric L, Shaw PW, Davidson NE. Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. Breast Cancer Res. Treat., 131:777-89, 2012. PMID:21452019
- Huang Y, Nayak S, Jankowitz R, Davidson NE, Oesterreich S. Epigenetics in breast cancer-what’s new? Breast Cancer Res., 13(6):225, 2011. PMID: 22078060
- Huang Y, Stewart TM, Wu Y, Baylin SB, Marton LJ, Woster PM, Casero RA. Novel oligoamine analogues inhibit lysine-specific demethylase 1 (LSD1) and induce re-expression of epigenetically silenced genes. Clin. Cancer Res., 15:7217-28, 2009. PMID: 19934284
- Huang Y, Greene E, Stewart TM, Goodwin AC, Baylin SB, Woster PM, Casero RA. Inhibition of the lysine specific demethylase, LSD1, by novel polyamine analogues results in re-expression of aberrantly silenced genes. Proc Natl Acad Sci USA, 104(19): 8023-8028, 2007. PMID: 17463086
For additional publications, visit Pubmed.