Email

chonghui.cheng@bcm.edu

Positions

Professor

Lester and Sue Smith Breast Center
Baylor College of Medicine
Houston, TX US

Professor

Molecular and Human Genetics
Baylor College of Medicine

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

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.

Websites

Selected Publications

• Hu X, Harvey SE, Zheng R, Lyu J, Grzeskowiak CL, Powell E, Piwnica-Worms H, Scott KL, Cheng C "The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing." Nat Commun.. 2020;11: 486 Pubmed PMID: 31980632
• 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 "CD44 splice isoform switching determines breast cancer stem cell state." Genes Dev. 2019;33:166-179. Pubmed PMID: 30692202
• Zhang J, Harvey SE, Cheng C "A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes." Nucleic Acids Res. 2019;47:3667-3679. Pubmed PMID: 30698802
• Huang H*, Zhang J*, Harvey SE*, Hu X, Cheng C "RNA G-quadruplex secondary structure promotes alternative splicing via the RNA binding protein hnRNPF." Genes Dev.. 2017;31:2296-2309. Pubmed PMID: 29269483

Funding

Regulation and consequences of cryptic splicing - #R35 GM131876

(04/01/2024 - 03/31/2029) NIH/NIGMS

Mechanisms of tumor cell clustering in breast cancer metastasis - #R01CA276432

(07/28/2023 - 06/30/2028) Grant funding from NIH/NCI

Integrative Single-Cell Analyses of Circulating Tumor Cells - #HT94252310753

(08/01/2023 - 07/31/2026) Grant funding from DoD