THE MARIS LABORATORY
Our research is focused on neuroblastoma, a common and often devastating childhood cancer of the peripheral nervous system. We strive to have a truly translational research program by taking clinical observations to the laboratory, and our laboratory discoveries back to the clinic. Our goal is to have a comprehensive approach to neuroblastoma, and this has resulted in a diverse laboratory environment with multiple projects focusing on the common endpoint of improved cure rates for this frequently lethal childhood malignancy.
The major NIH funded projects currently active in the Maris lab can be broken down into 5 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; 3) using genetic approaches to define the unique features of neuroblastoma vascular biology including functional validation in murine models; 4) applied research with novel compounds targeting neuroblastoma-specific alterations in murine models; and 5) developing array-based high throughput methods for solid tumor molecular diagnostics. We use both traditional (linkage analysis, positional cloning) and newer array-based (oligonucleotide array-based expression profiling, SNP chips, BAC array-based comparative genomic hybridization) genetic approaches, and transgenic murine models as tools for each of these main areas of research. This has led to the discovery of chromosome band 16p13 as a neuroblastoma predisposition locus, PHOX2B as a neuroblastoma predisposition gene, chromosome region 11q14-23 as a major metastasis suppressor locus, and multiple pro-angiogenic signalling pathways susceptible to inhibition strategies we have developed in vitro and in vivo . We have also developed novel “functional genomic” approaches to gene discovery, as well as in-house SNP-based microarrays for a variety of applications. Recently initiated projects include a whole genome association study in thousands of neuroblastoma patients using a 500K SNP platform and a whole "kinome" screen using siRNA knockdown for new molecular targets.
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 (CHOP; www.chop.edu ). Beside participation in Children's Oncology Group (COG; www.childrensoncologygroup.org ) clinical trials, a Neuroblastoma Developmental Therapeutics Research Team participates in New Approaches to Neuroblastoma Therapy (NANT; www.nant.org ) Phase 1 clinical trials and CHOP investigator initiated Phase 1 and 2 clinical trials. Dr. Maris is the Chair of the Neuroblastoma Disease committee within the COG, allowing for translational potential on a national scale. For example, our discovery that 1p and 11q LOH is prognostically important is now incorporated as a standard assay in our national Phase III trial. 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.
For more information about the Maris lab, please visit the maris laboratory and research program website.