Research

Dr. Zhu’s research findings in cancer research, particularly in the fields of brain tumors and neurofibromatosis type 1 (NF1) field have been published in highly selective journals, such as Science, Cell, Nature Reviews Cancer, Cancer Cell, Nature Genetics, eLife, Cell Reports, Nature Communications, and Developmental Cell. Dr. Zhu’s work has yielded major functional, molecular, and mechanistic insights into the mechanisms by which alterations in the NF1 tumor suppressor gene (TSG) as well as other TSGs (e.g. p53) contribute to developmental alterations in the brain. His work has contributed to understanding of the development and clinical behaviors of tumors arising in individuals with the NF1 condition as well as in a range of common cancer types where NF1 gene alterations arise somatically and consequently abnormally activate RAS-mediated ERK/MAPK signaling during cancer development. Dr. Zhu’s recent work has led to a Department of Defense-sponsored clinical trial for NF1-associated malignant peripheral nerve sheath tumors.

We are investigating 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).

Using a series of genetically engineered mutant animals, we are exploring how tumor suppressor genes regulate growth and transformation of neural stem/progenitor cells in vivo and in vitro, the lineage relationship between neural stem and progenitor cells or differentiated cells and malignant tumors in the nervous system, and the molecular mechanism(s) underlying malignant transformation.