Email

xiaoyonf@bcm.edu

Positions

Assistant Professor

Breast Center
Department of Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas United States

Member

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States

Member

The Therapeutic Innovation Center
Baylor College of Medicine
Houston, Texas United States

Education

MD from Second Military Medical University

06/1998 - Shanghai, China

Clinical Anesthesiology

PhD from Second Military Medical University

06/2003 - Shanghai, China

Biochemistry and Molecular Biology

Postdoctoral Training at Baylor College of Medicine

07/2009 - Houston, Texas United States

Cancer multi-OMICS and Targeted Therapy and Resistance

Professional Interests

• Cancer epitranscriptomics, Multi-OMICS integration, Functional genomics

Professional Statement

Dysregulated cancer epitranscriptomics in targeted therapy resistance
Cancer arises from genetic alterations that invariably lead to dysregulated epigenetic and transcriptional programs. These dysregulated epitranscriptomic events eventually reprogram cancer cells to survive targeted therapies and promote cancer progression and metastasis. Endocrine therapy targeting estrogen receptor (ER), the master transcription factor in ER+ breast cancer, is effective but resistance is common. So far there are few druggable transcription factors, other than ER, are available in clinic. We have recently reported gene amplification and/or overexpression of the forkhead box protein A1 (FOXA1), a pioneer transcription factor for ER-chromatin binding and function, in both preclinical resistance models and clinical specimens of endocrine-resistant metastatic breast cancer. We are currently using integrated multi-OMICS approach and functional genomics to identify novel key downstream effectors of high FOXA1-induced enhancer and transcriptional reprogramming, using our unique panel of resistance models including patient-derived organoids and xenografts. In addition, our research of lineage-specific master transcription factors leads to investigation of new therapeutic strategies to treat other forms of malignancies, including metastatic pancreatic cancer, which shares the similar mechanism of dysregulated epitranscriptomics induced by FOXA1 augmentation.
Discovery of druggable vulnerabilities of therapy-resistant tumors
Recent studies of large-scale screening reveal gene dependency (e.g., by RNAi) and drug sensitivity across a large body of human cancer cell lines. We are currently employing an in silico bioinformatics approach to integrate and analyze data from studies including CCLE (Cancer Cell Line Encyclopedia, Cancer Dependency Map) and GDSC (Genomics of Drug Sensitivity in Cancer). Our primary aim is to nominate genes as new therapeutic vulnerabilities to treat specific forms of cancer with unique genetic background and variant drug responsiveness. Our initial efforts focus on the vulnerabilities of anti-CDK4/6-resistant ER+ breast cancer with promising results undergoing further functional validation.

Websites

Selected Publications

• Fu X, Jeselsohn R, Pereira R, et al. "FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer." Proc Natl Acad Sci USA. 2016 113 : E6600-E6609. Pubmed PMID: 27791031
• Fu X, Creighton CJ, Biswal NC, et al. "Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase." Breast Cancer Res. 2014 16 : 430. Pubmed PMID: 25212826
• Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM, Lluch A, Gray JW, Brown PH, Hilsenbeck SG, Osborne CK, Mills GB, Lee AV, Schiff R "Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer." Breast Cancer Res. 2010 12 (3): R40. Pubmed PMID: 20569503
• Fu X, Pereira R, De Angelis C, et al. "FOXA1 upregulation promotes enhancer and transcriptional reprogramming in endocrine-resistant breast cancer." Proc Natl Acad Sci U S A. 2019 December 11; doi: 10.1073/pnas.1911584116 : Pubmed PMID: 31826955

Funding

Targeting the Mechanism of Hyperactive FOXA1 in Transcriptional Reprogramming Toward Endocrine Resistance and Metastasis in Breast Cancer - #RP190398 (Co-PI)

(03/01/2019 - 02/28/2022) Grant funding from CPRIT

Skills

Functional genomics

Multi-OMICS integration

Cancer epitranscriptomics

Molecular biology

Bioinformatics