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Zhu Lab

Our Research

Neurofibromatosis Type 1

In addition to the high risk of developing tumors in the nervous system, approximately 30-70 percent of individuals with neurofibromatosis type 1 (NF1) have learning disabilities, representing the most significant cause of lifetime morbidity associated with this disease. The Zhu Laboratory is interested in understanding the role of NF1 in developing neural stem and progenitor cells and how its loss causes developmental abnormalities, leading to the structural brain defects associated with severe learning disabilities in humans, and the development of benign peripheral nerve sheath tumor – plexiform neurofibroma in the peripheral nervous system (PNS), and optic pathway glioma in the central nervous system (CNS). The research group of Yuan Zhu, Ph.D., is investigating the mechanism underlying these NF1-associated diseases and performing preclinical studies with animal models. Our goal is to integrate basic, translational and clinical research to develop novel preventive and treatment therapies for NF1-associated diseases.

High-Grade Glioma and Glioblastoma 

NF1 tumor suppressor gene is one of the most frequently mutated genes in high-grade glioma and glioblastoma (GBM) – the most frequent and lethal brain cancer in humans. However, the development of GBM in individuals afflicted with NF1 is not common. Using GEM models, we have demonstrated that inactivation of NF1 is not a robust oncogenic event unless it occurs in the context of p53 loss. Thus, sequential inactivation of tumor suppressor genes p53 and NF1 is required for effectively transforming neural stem and progenitor cells in the subventricular zone (SVZ) of the lateral ventricle. These studies have established NF1 as a context-dependent tumor suppressor gene in GBM, providing the mechanism by which most individuals with NF1 have no increased risk of developing GBM. We are exploring these mouse models to address:

  1. How the tumor suppressor genes p53 and NF1 regulate growth and transformation of neural stem/progenitor cells in vivo and in vitro?
  2. What is the lineage relationship between neural stem and progenitor cells or differentiated cells and GBM in the nervous system?
  3. What is the molecular mechanism(s) underlying the development of astrocytomas/GBM and malignant peripheral nerve sheath tumors (MPNSTs) from normal neural stem and progenitor cells?