Mark A. Israel, MD

Professor of Pediatrics and Genetics
Director Norris Cotton Cancer Center

Research Interests

All tumors are characterized by both inappropriate growth and anaplasia, the loss of differentiated characteristics. Research in Dr Israel's laboratory concerns the molecular pathways over which these two key biologic activities, growth and differentiation, are coordinately regulated. Investigations are also ongoing on the role of aberrations in these pathways in the development of cancer.

Recent work has been focused on the characterization and evaluation of Id genes. These genes encode transcription factors that function as dominant negative inhibitors of basic helix-loop-helix proteins, which mediate lineage-specific gene expression. Id genes are ubiquitously expressed throughout early development, though they are rarely expressed in tissues from adults. Work in this laboratory has shown that these genes are also highly expressed in many different types of brain tumors. Expression of Id-2 can enhance cell growth, and our work has determined that this is mediated through a direct interaction with the product of the retinoblastoma gene, a known tumor suppressor.

Ongoing work is focused on further characterization of the cellular pathways that mediate Id-gene induced cell growth. Experiments have been conducted to understand the precise cell types in which tumors of the CNS arise, and the molecular alterations that characterize histologically indistinguishable tumors of astrocytes are being studied. These studies have involved the identification of novel tumor markers, as well as the characterization of known tumor cell markers in various types of CNS tumors.

Of particular interest has been the examination of genes whose expression is regulated during the course of nervous system differentiation and oncogenes and tumor suppressor genes whose structure and expression is altered in brain tumors. A program has also been initiated to develop novel approaches to the management of brain tumors through gene transfer technologies. Work is in progress to develop strategies that involve the delivery of toxic metabolites to tumor cells by cells that are specifically targeted to neoplastic tissues.

Biosketch

Dr. Mark Israel is a noted clinician-scientist who received his undergraduate education at Hamilton College (1968) and his medical training from Albert Einstein College of Medicine (1973). After an internship and a residency at the Children's Hospital Medical Center in Boston, he moved to the NIH to pursue research at the National Institute of Allergy and Infectious Diseases. In 1981 he completed his training in pediatric oncology in the Pediatric Branch of the National Cancer Institute, where he ultimately became head of the Molecular Genetics Section in 1984.

In 1990 he moved to San Francisco as Professor of Neurological Surgery and Pediatrics to lead the Preuss Laboratory of Molecular Neuro-Oncology. From 1997 he was the Kathleen M. Plant Distinguished Professor. In 2001, Dr. Israel moved to Dartmouth Medical School as a Professor of Pediatrics and of Genetics and as Director of the Norris Cotton Cancer Center, an NCI-designated comprehensive cancer center.

Dr Israel is an accomplished, consistently funded investigator in the field of neuro-oncology and has published more than 200 peer-reviewed papers. He has been honored many times for his scientific contributions, and he received the Farber Award in 1998 for outstanding contributions to neuro-onoclogy. In addition, he has been recognized as an outstanding teacher throughout his career. Dr. Israel was a member of the NCI Board of Scientific Counselors, and has distinguished himself through his extensive service on society and charity advisory boards, scientific prize selection committees, and editorial boards including Cancer Research and Neuro-Oncology.