Genes, Genomics and Pediatric Disease
Center Leaders: Nancy Spinner, PhD and John Maris, MD
Genetics is a discipline with unique implications for pediatric medicine and impacts all aspects of childhood healthcare. The field has undergone tremendous growth in recent years as new technologies have allowed for increasingly precise probing of the genome. The recent completion of the Human Genome Project provided the essential roadmap for these studies while innovative genetic models of human disease and high-throughput technologies such as DNA microarrays have provided the tools necessary to exploit this information.
Genetics and genomic research at Children’s Hospital is multifaceted and spans many divisions. These research efforts are conducted in the Genes, Genomes and Pediatric Disease Research Affinity Group. The affinity group houses an outstanding program focused on the molecular genetic basis of human disease. Major recent advances include identifying the gene for the rare developmental disorder Cornelia deLange syndrome and identifying the role of mutations in a cellular signaling pathway, known as Notch2, in human disease.
Investigators are also focused on continuing their study of the 22q11.2 deletion syndrome – an abnormality of chromosome 22 that can lead to a myriad of health problems – increasing the understanding of the fatal nervous system disorder called Batten disease and gaining strides in unraveling the role of mutations in a tumor suppressing gene known as hSNF5/INI1 in causing certain pediatric tumors. Also, investigators are engaged in large collaborative research efforts focused on the interactions between human genes and environmental exposures.
Another area of investigation for affinity group members is neurogenetics. Investigators are studying the cause of several neurologic disorders, including various muscular dystrophies. They are actively involved in the clinical and research components of neurogenetics in order to understand the mutated genes and pathways and translate that understanding to diagnosis and treatment.
Cancer is a genetic disease and many Hospital investigators are focused on the genomics and proteomics of common pediatric cancers. Investigators have recently made major advances in understanding neuroblastoma – a form of cancer that occurs in infants and young children – including development of a more precise algorithm for predicting prognosis based on genetic alterations in the cancer cells. This work is being applied nationwide within the Children’s Oncology Group clinical trials network, a National Cancer Institute-supported group that coordinates cancer clinical trials at 238 member institutions, including cancer centers of all major universities and teaching hospitals.
Children’s Hospital investigators have made significant advances in understanding the underlying abnormalities in pediatric solid tumors and leukemias and translating these findings to the clinic. For example, by demonstrating that many neuroblastomas are dependent on activation of a gene called “Trk,” a specific inhibitor of Trk has been developed with a local pharmaceutical company and is now in clinical trials for children with neuroblastoma.
Because genomic medicine is by definition multidisciplinary, the formation of a research affinity group was a natural extension of ongoing collaborative research efforts at Children’s Hospital. Monthly affinity group meetings provide a forum to share and critique research programs and to develop strategic goals. The affinity group also has a successful monthly seminar series that draws international experts from around the country, and provides a forum for establishing or extending collaborations with colleagues at the University of Pennsylvania.
The affinity group also consults an external advisory committee of international experts to critique its program and provide advice on genetics and genomics research at Children’s Hospital and the University of Pennsylvania.