Chonghui Cheng, M.D., Ph.D.
Professor
Positions
- Professor
-
Lester and Sue Smith Breast Center
vlog of Medicine
Houston, TX, US
- Professor
-
Molecular and Human Genetics
vlog of Medicine
- Professor
-
Department of Molecular and Cellular Biology
vlog of Medicine
Houston, Texas
- Member
-
Dan L Duncan Comprehensive Cancer Center
vlog of Medicine
Houston, Texas, United States
Education
- MD from Peking University Health Science Center
- Beijing, China
- PhD from Sloan-Kettering Institute/Cornell University Weill Graduate School of Medical Sciences
- New York, New York, United States
- Postdoctoral Fellowship at Massachusetts Institute of Technology
- Cambridge, Massachusetts, United States
Honors & Awards
- CPRIT Scholar in Cancer Research
- Cancer Prevention Research Institute of Texas (CPRIT) (06/2016 - 05/2021)
- American Cancer Society Research Scholar
- American Cancer Society (01/2009 - 01/2014)
- Lynn Sage Scholar
- Lynn Sage Foundation (01/2011 - 01/2013)
- Career Development Award
- American Association for Cancer Research (01/2008 - 01/2010)
Professional Interests
- RNA Binding Proteins
- Alternative Splicing
- Breast Cancer Metastasis
- Clinical Applications
- Multi-Omics
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.
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
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Hu X, Harvey SE, Zheng R, Lyu J, Grzeskowiak CL, Powell E, Piwnica-Worms H, Scott KL, Cheng C. " " Nat Commun.. 2020 ; 11: 486
Pubmed PMID: . -
Zhang H, Brown RL, Wei Y, Zhao P, Liu S, Liu X, Deng Y, Hu X, Zhang J, Gao XD, Kang Y, Mercurio AM, Goel HL, Cheng C. " " Genes Dev. 2019 ; 33 : 166-179.
Pubmed PMID: . -
Zhang J, Harvey SE, Cheng C. " " Nucleic Acids Res. 2019 ; 47 : 3667-3679.
Pubmed PMID: . -
Huang H*, Zhang J*, Harvey SE*, Hu X, Cheng C. " " Genes Dev.. 2017 ; 31 : 2296-2309.
Pubmed PMID: .
Funding
-
Regulation and consequences of cryptic splicing
#R35 GM131876 - (04/01/2024 - 03/31/2029)
- NIH/NIGMS
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Mechanisms of tumor cell clustering in breast cancer metastasis
#R01CA276432 - (07/28/2023 - 06/30/2028)
- Grant funding from NIH/NCI
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Integrative Single-Cell Analyses of Circulating Tumor Cells
#HT94252310753 - (08/01/2023 - 07/31/2026)
- Grant funding from DoD
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