Xiyuan Zhang, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 10, 1W-3750
- Bethesda, MD, 20892
- 240-858-3835
- xiyuan.zhang@nih.gov
RESEARCH SUMMARY
Xiyuan Zhang is a cancer biologist whose research program studies the role of epigenetic mechanisms of oncogenic activation during the malignant transformation of benign neurofibromatosis type 1 (NF1)-associated nerve sheath tumor to malignant peripheral nerve sheath tumors, using molecular, epigenetic, cellular and model system approaches. She pioneers the application of single-cell sequencing in understanding the complicated intra-tumoral heterogeneity in pediatric cancers and rare tumors.
Areas of Expertise
Xiyuan Zhang, Ph.D.
Research
Patients with NF1 have a life-time risk of developing malignant peripheral nerve sheath tumor (MPNST), a devastating illness. MPNST is the product of a process called malignant transformation, during which benign plexiform neurofibroma (PN) progresses through the precancerous atypical neurofibroma (AN) accompanied by oncogenic activation. While PN alone can be effectively treated by the FDA-approved drug selumetinib, there is currently no effective targeted therapy for MPNST besides complete surgical removal with wide negative margin. This treatment is often difficult due to the location of the tumor and the complex involvement of nerves. It is therefore critical to prevent MPNST by detecting the PN and AN that are at risk of undergoing malignant transformation.
My research program aims to address these needs through ongoing research projects:
1. Identification of epigenetic regulators that positively and negatively regulate the activation of oncogenes during the malignant transformation of NF1 tumors.
2. Characterization of gene expression changes over the course of tumor progression by using patient samples and human cell lines derived from patient tumors
3. Evaluation of the role that extra chromosomal DNA (ecDNA) plays in driving malignant transformation in high-risk PN and AN.
Biography
Xiyuan Zhang, Ph.D.
Dr. Zhang received her PhD in Cancer Biology from Georgetown University Lombardi Comprehensive Cancer Center for her doctoral training in Dr. Leena Hilakivi-Clarke’s laboratory. Her thesis research focused on the timing of dietary exposures and its impact on breast cancer treated with the anti-estrogen agent tamoxifen. Xiyuan became an expert in developing preclinical rodent models of estrogen positive breast cancer and used them to study the impact of bioactive compounds and maternal obesity on tamoxifen resistance. Dr. Zhang was awarded and served as the principle investigator on a graduate student research award investigating the transcriptomic alterations in mammary glands caused by in utero high-fat diet exposure.
Dr. Zhang’s postdoctoral research in Dr. Jack Shern’s laboratory in the POB focused on investigating the genetic and epigenetic alterations associated with the malignant transformation of Schwann cell-originated plexiform neurofibroma to malignant peripheral nerve sheath tumor (MPNST) in patients with NF1. While loss of the functional polycomb repressive complex 2 (PRC2) has been observed in most MPNSTs, the associated epigenetic consequences of PRC2 loss remain unclear. Dr. Zhang’s broad background in cancer biology, epigenetics, and bioinformatics enables her to establish novel research areas in the laboratory and develop novel analytic pipelines for large-scale data analysis. She has been successful in: 1) demonstrating that PRC2 loss corrupts the enhancer landscape of a normal Schwann cells and causes an abnormal transcriptional circuitry that drives the oncogenic program of MPNST; 2) performing integrative analysis of single-cell sequencing data to demonstrate that PRC2-deficient MPNST cells are phenotypically stuck at a de-differentiated stage of a normal developmental trajectory. Dr. Zhang is a recipient of the Early Investigator Research Award and a Concept Award from the Department of Defense, Scholar-in-Training Award, and Women in Cancer Research Award from the American Association for Cancer Research.