
Websites
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Positions
- Associate Professor
- Lester and Sue Smith Breast Center
- Baylor College of Medicine
- Houston, TX, US
- Associate Professor
- Molecular and Human Genetics
- Baylor College of Medicine
- Associate Professor
- Department of Molecular and Cellular Biology
- Baylor College of Medicine
- Houston, Texas
- Member
- Dan L Duncan Comprehensive Cancer Center
- Baylor College of Medicine
- Houston, Texas, United States
Education
- MD from Peking University Health Science Center
- PhD from Sloan-Kettering Institute/Cornell University Weill Graduate School of Medical Sciences
- Postdoctoral Fellowship at Massachusetts Institute of Technology
Honors & Awards
- Career Development Award
- American Cancer Society Research Scholar
- Lynn Sage Scholar
- CPRIT Scholar in Cancer Research
Professional Interests
- RNA
- Alternative splicing
- Breast Cancer Metastasis
- Clinical Applications
Professional Statement
In the Cheng lab, we strive to understand the fundamental questions of how RNA regulation controls cellular processes in normal biology and in the context of cancer. Working at the interface of RNA splicing and breast cancer biology, our current focus is on regulation of breast cancer metastasis driven by alternative splicing. We use molecular biology, genomics, and bioinformatics approaches in conjunction with genetic models and patient samples to discover rules and networks that regulate metastasis and associated processes. We work closely with physician scientists and aim to apply our findings from basic research to the development of prognostic markers and therapeutics for the treatment of breast cancer.
The developmental program Epithelial-Mesenchymal Transition (EMT) is frequently re-activated in metastatic and recurrent tumors. Our work provided a conceptual understanding depicting a causal role for RNA alternative splicing in EMT and breast cancer recurrence. We found that splice isoform switching of the CD44 gene must take place in order for cells to undergo EMT. We also discovered a novel splicing-mediated pathway that drives cancer metastasis. We demonstrated that the RNA binding protein hnRNPM reprograms alternative splicing including CD44 and promotes a breast cancer metastatic phenotype. By competitive binding on cis-regulatory RNA elements, hnRNPM activates a mesenchymal splicing program in a cell-type restricted manner, emphasizing a tightly regulated splicing program during tumor metastasis. We are combining patient data biocomputing analysis with cell-based and animal experiments to determine the networks of RNA regulation that governs the phenotype of breast cancer metastasis.
In collaboration with nano-technology engineers, we developed the “NanoFlare” method that enables the detection and isolation of live circulating tumor cells (CTC), establishing a platform to study splicing-mediated cancer cell plasticity and phenotypes in patient-derived samples. We are continuing on this collaboration to develop novel tools for the prognosis and diagnosis of breast cancer.
We have been intrigued by the fact that nearly all human genes are detected to undergo alternative splicing, vastly expanding the human proteomes. Therapeutic resistance of promising anti-tumor drugs, such as the anti-HER2 antibody Trastuzumab and the B-RAF(V600E) inhibitor Vemurafenib, is now known to be caused by aberrantly spliced HER2 and B-RAF. Despite these important observations, alternative splicing in cancer has remained largely an untargeted territory. We are actively looking for dedicated research fellows to join us to understand the contribution of RNA regulation in breast cancer metastasis and to apply it to clinical settings.
Selected Publications
- Liu S, Cheng C. "Akt Signaling Is Sustained by a CD44 Splice Isoform-Mediated Positive Feedback Loop.." Cancer Res. 2017;77:3791-3801. Pubmed PMID: 28533273
- Wang W, Zhang H, Liu S, Kim CK, Xu Y, Hurley LA, Nishikawa R, Nagane M, Hu B, Stegh AH, Cheng SY, Cheng C. "Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A.." Proc Natl Acad Sci U S A. 2017;114:8366-8371. Pubmed PMID: 28716909
- Zhao P, Xu Y, Wei Y, Qiu Q, Chew TL, Kang Y, Cheng C. "The CD44s splice isoform is a central mediator for invadopodia activity." J Cell Sci. 2016;129:1355-1365. Pubmed PMID: 26869223
- Xu Y, Gao XG, Lee JH, Huang H, Tan H, Ahn J, Reinke L, Peter ME, Feng Y, Gius D, Siziopikou KP, Peng J, Xiao X, Cheng C. "Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing." Genes Dev. 2014;28:1191-1203. Pubmed PMID: 24840202
- Brown RL, Reinke LM, Damerow MS, Perez D, Chodosh LA, Yang J, Cheng C. "CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression." J Clin Invest. 2011;121:1064-1074. Pubmed PMID: 21393860
- Zhao P, Damerow MS, Stern P, Liu AH, Sweet-Cordero A, Siziopikou K, Neilson JR, Sharp PA, Cheng C. "CD44 promotes Kras-dependent lung adenocarcinoma." Oncogene. 2013;32:5186-90. Pubmed PMID: 23208496
- Reinke LM, Xu YL, Cheng C. "Snail represses the splicing regulator ESRP1 to promote epithelial-mesenchymal transition." J Biol Chem. 2012;287:36435-42. Pubmed PMID: 22961986
- Harvey SE, Cheng C. "Methods for Characterization of Alternative RNA Splicing." Methods Mol Biol. 2016;1402:229-41. Pubmed PMID: 26721495
- Halo T, McMahon KM, Angeloni NL, Wang W, Xu Y, Malin D, Strekalova E, Cryns VL, Cheng C*, Mirkin CA*, Thaxton CS*. "NanoFlares for the detection, isolation, and culture of live tumor cells from human blood." PNAS. 2014;111:17104-17109. Pubmed PMID: 25404304
- Huang H, Xu Y, Cheng C. "Detection of alternative splicing during epithelial-mesenchymal transition." J Vis Exp. 2014 October 9;92:e51845. Pubmed PMID: 25350517
- Liu S and Cheng C. "Alternative RNA Splicing and Cancer." Wiley Interdiscip Rev RNA. 2013;4:547-66. Pubmed PMID: 23765697
Funding
- Alternative RNA Splicing of CSF3R in Promoting Myelodysplastic Syndromes - #W81XWH-15-1-0153
- DOD/U.S. Army Medical Research and Materiel Command
- Mechanisms of hnRNPM in Alternative Splicing Regulation During EMT - #R01GM110146
- NIH/NIGMS
- Investigating the Mechanisms of CD44s Splice Isoform in Breast Cancer Metastasis - #R01CA182467
- NIH/NCI
- Cancer Prevention Research Institute of Texas (CPRIT)
- CPRIT Scholar in Cancer Research