John Maris Laboratory

Led by John M. Maris, MD, researchers in the Maris Laboratory are focused on understanding the underlying molecular and genetic mechanisms that contribute to the development and progression of pediatric neuroblastoma. Also, efforts in the Maris Laboratory are dedicated to the development of new molecular diagnostic tests and less toxic, targeted cancer therapies to treat relapsed or refractory neuroblastoma. The long-term goal of the work in this laboratory is to use a multidisciplinary approach to improve existing cure rates for children with neuroblastoma.

Ongoing studies in the Maris Laboratory are using functional genomics, whole genome sequencing, SNP analyses and proteomics to genetically profile neuroblastomas from thousands of pediatric cancer patients. The goal of this effort is to identify specific mutations and/or signature DNA sequences that can be used to predict disease progression, select appropriate treatment options for specific tumor types and to identify molecular targets for development of new targeted cancer therapies.

Other studies in the Maris Laboratory are focused on cataloging the mutational heterogeneity of different pediatric neuroblastomas with the goal of developing patient-specific therapies that target unique oncogenic drivers of individual tumors. The use of this type of molecular analysis in preclinical testing will help to inform the design of early phase clinical trials by identifying patients with a particular molecular tumor type who might benefit the most when evaluating experimental cancer therapies.

Additional studies in the Maris Laboratory are examining the use of the injectable alpha-emitting radionuclide mta-211[At] astatobenzylguanidine (MABG) as a targeted therapy to treat relapsed pediatric neuroblastoma. MABG, a functional analogue of the neurotransmitter norepinephrine, is selectively taken up and sequestered in neuroendocrine tumors including neuroblastoma. Early laboratory results suggest that MABG therapy may be effective and less toxic than existing radiotherapies for neuroblastoma.

A major clinical focus in the Maris Laboratory is participation in the Next Generation Personalized Neuroblastoma Therapy (NEPENTHE) clinical trial. The role of the Maris Laboratory in this trial is to determine the DNA sequence of tumors biopsied from pediatric patients with relapsed neuroblastoma. Based on the genetic profile of individual tumors, children will be assigned to one of three treatment groups that target different genetic pathways involved in neuroblastoma tumorigenesis.  The overarching goal of the NEPENTHE trial is to use molecular profiling to determine the best therapeutic options for children with relapsed or refractory neuroblastoma.

Future studies in the Maris Laboratory will continue to focus on developing molecular tools to better predict neuroblastoma disease progression, select appropriate treatment options for individual neuroblastoma tumor types and to aid in the design of clinical trials to new targeted cancer therapies to improve the cure rates for pediatric neuroblastoma.