Lai Man (Natalie) Wu , PhD

Cincinnati Children’s Hospital Medical Center

Identification of cellular diversity and tumor-initiating cells driving NF-to-MPNST and drug resistance by single-cell multiomics for targeted therapy

Neurofibromatosis type I (NF1), an inherited condition in children, affects one in every 3,000 individuals worldwide. Although benign in nature, in some cases, the slowly growing NF1-mutated nerve tumors can become malignant peripheral nerve sheath tumors (MPNST), killing 50% of the patients within five years. Dr. Wu’s Powered by Pablove research projects aim to unravel the puzzle of how benign neurofibromas (NF) become cancerous MPNST. 

In Dr. Wu’s own words: 

Neurofibromatosis type I (NF1), an inherited condition in children, affects one in every 3,000 individuals worldwide. Although benign in nature, in some cases, the slowly growing NF1-mutated nerve tumors can become malignant peripheral nerve sheath tumors (MPNST), killing 50% of the patients within five years. How benign neurofibromas (NF) become cancerous MPNST is still a puzzle. These tumors start from a specialized cell called Schwann cell in the nerves. One of the promising ways to treat MPNST is to target the specific signaling pathways that cause tumor formation and progression. To achieve this, it is important to learn about what causes normal Schwann cells to become benign NF1 tumors, which eventually turn into MPNST. We use single-cell transcriptomics and epigenomics that enable us to detect what genes a cell expresses and what networks control this expression at very high resolution. Single-cell data can tell us what cell populations are within a tumor and how they talk to one another to make the tumor grow deadlier. Rare cells, called cancer stem cells, stay dormant but can turn into deadly cancer cells after treatment causing relapse. Also, immune system cells are abundant in tumors. All these cells interact with tumor cells, creating a highly dynamic ecosystem. My research will find out how these cancer stem cells and tumor microenvironment may cause transition of benign NF into MPNST, and develop better tools to specifically attack the tumor.

Awarded in 2020