As a pediatric oncologist, my research goals are to develop more effective and less toxic therapies for childhood cancers with a special focus on neuroblastoma. This MYCN-driven malignancy of the peripheral sympathetic nervous system accounts for 13% of all pediatric cancer deaths. I have recently relocated to assume the position as Division Chief for Pediatric Hematology/Oncology at University of Massachusetts Medical School in Worcester, Ma. This is after 19 years as co-chair of the Neuroblastoma Research program at Texas Children’s Cancer Center, Baylor College of Medicine. The UMass Medical School and UMass Memorial Clinical organizations provides exceptional support and research infrastructure for basic and translational efforts. I am an affiliated member of the Cancer Biology program, the MD, PhD program and the division of Molecular, Cell and Cancer Biology (MCCB). 

A major focus of my laboratory is characterizing the role of MYCN in neuroblastoma pathogenesis and tumor stem cell biology. We have defined a novel tumor subpopulation meeting criteria as cancer stem cells or tumor initiating cells. That is the ability to self-renew, differentiate and recapitulate all the subsets of cells making up a complex tumor in vivo. We are further characterizing intra-tumor heterogeneity using single cell approaches.  

As part of this work we have characterized multiple direct transcriptional targets of MYCN which are either destabilize p53 (e.g. MDM2) or alter transcriptional pathways to promote proliferation and inhibit apoptosis (e.g. MCM7 or mir-34a). This work has involved developing novel transgenic mouse models, optimized orthotopic xenografts and conditional cell lines for gain and loss of function studies of both microRNAs and coding genes. Our most recent efforts resulted in defining a novel direct binding interaction of MYCN with p53 that reveals a novel oncogenic function for MYCN as a direct transcriptional cofactor for p53.

Student rotation projects forcussed on cancer stem cells, chromatin profiling, and structural characterization of transcription factor/DNA interactions are available. 

Our laboratory has a number of projects and opportunitys to learn in vivo tumor modeling and translation oncology research.