Yanxin Pei is currently Assistant Professor at Children's National Medical Center in Washington, D.C. She earned her PhD from the Department of Neuroscience in Tsinghua University, China. Her doctoral thesis work focused on cellular therapy for Parkinson's disease. She successfully induced embryonic stem cells to differentiate into dopaminergic neurons that can survive and integrate into host tissue after transplantation, which significantly reduced the symptoms of Parkinson's disease in a mouse model. After completing her PhD, Yanxin joined Dr. Robert Wechsler-Reya's lab in Duke University as a postdoc, and then moved with Dr. Wechsler-Reya to the Sanford-Burnham Institute, where she was promoted to Research Assistant Professor. During her training in Dr. Wechsler-Reya's lab, Yanxin developed a mouse model for Group 3 medulloblastoma by overexpressing MYC and mutant p53 in cerebellar stem cells, which provided a valuable tool to identify and test novel therapies. Using this model, she demonstrated that HDAC and PI3K antagonists cooperate to inhibit growth of MYC-driven medulloblastoma. After completing her postdoc training, Yanxin started her own lab at Children's National Medical Center in Washington in 2014, where she developed a novel mouse model for Group 3 medulloblastoma. She found that the MYC oncogene alone is sufficient to induce tumorigenesis in granule neuron progenitors and Bergmann glia, without requiring p53 mutation. This model faithfully recapitulates human Group 3 medulloblastoma in terms of histology and gene expression profiles. She aims to use this model to test a novel targeted therapy for treating Group 3 medulloblastoma.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Based on extensive genomic analysis, MB has been classified into four major subtypes. Among these, tumors associated with overexpression or amplification of the oncogenic gene MYC have the poorest prognosis. Even with an intensive regimen of surgery, radiation and chemotherapy, 30 to 40 percent of patients exhibit tumor recurrence and die from their disease. One important cause of relapse is the small number of tumor cells that are initially resistant to radiation and chemotherapy. These cells may become activated and expand into a therapy-resistant and ultimately lethal tumor. Our laboratory, led by Yanxin Pei, PhD, is interested in understanding the mechanisms of therapy resistance and finding ways to target the resistant tumor cells, using both mouse MYC-driven MB model and human MYC-driven MB xenografts.
Our laboratory is also interested in investigating how oncogenes initiate and sustain tumorigenesis in MYC-driven MB. We have developed model systems whereby we can conditionally alter the expression of oncogenes in tumor cells. We are using these model systems to study whether:
- Inactivation of one oncogene can be sufficient to cause complete tumor regression.
- Some tumor cells escape dependence on oncogene and acquire additional genetic mutations during oncogene inactivation.
- These mutations can be new therapeutic targets to combine with oncogene inactivation to prevent tumor recurrence in MB.