Modelling neuroblastoma using human trunk neural crest cells
Tanmoy Mondal's group focuses on neuroblastoma (NB), a childhood cancer. NB is thought to be derived due to lack of differentiation of trunk neural crest cells (tNCC) during embryonic development. MYCN oncogene amplification is the most common genomic aberration in NB. 50 percent of NB patients with aggressive form of the disease, often do not respond to currently available therapy and better treatment strategies are required for these patients. Understanding how MYCN promotes tumor formation in NB can give us clues on how to treat NB patients who have aggressive disease with MYCN amplification.
Neuroblastoma (NB) is a childhood cancer which contributes to approximately 15 percent of all pediatric cancer related deaths. NB is a heterogeneous disease; non-high risk NB patients show good prognosis but high-risk NB patients often do not respond to multimodal therapy with frequent relapse. This suggests we need better understanding of the disease mechanism for effective treatment strategies for high-risk NB patients. MYCN amplification is one of the most frequent genetic aberrations observed in neuroblastoma and MYCN amplification often associated with aggressive disease. Neuroblastoma is thought to develop because of improper differentiation of the trunk neural crest cells (tNCCs) which normally contributes to sympathetic nervous system. Though role of MYCN in NB tumorigenesis has been studied using mouse model system but important difference exists between mouse and human NCCs which demands novel model system. MYCN amplified cell lines are, one such model system which has been explored to understand MYCN function in these cells but in these cell line model we lack the information what are early events which prevent differentiation of the tNCCs which leads to NB tumor formation. In our laboratory, we have developed human tNCCs in vitro by differentiating human ES cells and using these tNCCs we are trying to model the MYCN mediated tumorigenesis. Using transcriptomics and epigenomics based approaches we aim to decipher the early events during MYCN mediated oncogenesis. We hope our study of MYCN mediated oncogenesis using human tNCC model will provide us better understanding of the NB disease which can be exploited further for therapeutic intervention.
Department of Laboratory Medicine,
Institute of Biomedicine
Ketan Thombare, Ph D student
Roshan Vaid, Associated researcher
Aqsa Ali Rehan, Master thesis student
Saif Shehata, Master thesis student
Akram Mendez, Postdoctoral Research Fellow
Rebeca Burgos, Postdoctoral Research fellow.