The Focus of Our Research
Our research is focused on neuroblastoma, a common and often devastating childhood cancer of the peripheral nervous system. The goal of our program is to have a comprehensive experimental approach to neuroblastoma with the common endpoint of improved cure rates for this frequently lethal childhood malignancy. We strive to have a truly translational research program by taking clinical observations to the laboratory, and by taking laboratory discoveries back to the clinic.
The major NIH-funded projects currently active in the Maris lab can be broken down into four main themes: (1) determining the genetic events that initiate neuroblastoma tumorigenesis; (2) determining the somatically acquired genomic aberrations and genes responsible for the diverse clinical phenotype observed in patients with neuroblastoma; (3) using genetic approaches to define the unique features of neuroblastoma vascular biology, including functional validation in murine models and applied research with novel compounds targeting neuroblastoma vasculature in partnership with industry; and (4) developing array-based high throughput methods for solid tumor molecular diagnostics.
The clinical component of our research effort involves a variety of Phase I and II clinical trials. In many cases, the preclinical rationale for using these agents was developed in our lab or others at The Children's Hospital of Philadelphia. In addition to our participation in Children's Oncology Group (COG) clinical trials, our Neuroblastoma Developmental Therapeutics Research Team participates in the New Approaches to Neuroblastoma Therapy (NANT) program, which includes Phase 1 clinical trials and Children's Hospital investigator-initiated Phase I and II clinical trials. We seek to have a portfolio of open clinical trials available to patients with refractory neuroblastoma with the ultimate goal of moving many of these agents into front line treatment regimens.
We use both traditional methods (linkage analysis and positional cloning), newer array-based genetic approaches (oligonucleotide-based DNA copy number and mRNA expression profiling), and transgenic murine models as tools for each of these main areas of research. Using these methods we have identified chromosome band 16p13 as a neuroblastoma predisposition locus, PHOX2B as a neuroblastoma predisposition gene, and chromosome region 11q14-23 as a major metastasis suppressor locus. We have also found multiple pro-angiogenic signaling pathways that are susceptible to inhibition strategies and have developed them in vitro and in vivo. We have developed novel "functional genomic" approaches to gene discovery, as well as in-house SNP-based microarrays for a variety of applications. Recently, we have embarked upon a genome-wide association study using thousands of patient samples to determine the genetic alterations that predispose to neuroblastoma development, and are associated with the disease type ultimately seen in children.
The clinical component of our research effort involves a variety of Phase I and II clinical trials including agents where the preclinical rationale was developed in our lab, or in others at The Children’s Hospital of Philadelphia. In addition to participation in Children’s Oncology Group clinical trials, a Neuroblastoma Developmental Therapeutics Research Team participates in New Approaches to Neuroblastoma Therapy Phase I clinical trials and Hospital investigator initiated Phase I and II clinical trials. We seek to have a portfolio of open clinical trials available to patients with refractory neuroblastoma with the ultimate goal of moving many of these agents into front line treatment regimens.