- Professor, Department of Pediatrics, Section of Hematology/Oncology, Committee on Cancer Biology
- Director, Clinical Sciences
M.D., University of Illinois at Chicago 1980
B.A., Northwestern University 1976
The University of Chicago
AMB N114, (MC 4060)
5841 South Maryland Avenue
Chicago, Illinois 60637
Phone: (773) 702-2571
Biology of Neuroblastoma and Potential Therapeutic Targets
The over-all research focus of the Cohn laboratory is investigating the biology of the clinically heterogenous pediatric cancer, neuroblastoma and using this information to develop more effective, targeted therapy. Previous work has demonstrated that angiogenesis plays a clinically role in aggressive, high-risk neuroblastoma. In contrast, Schwannian-rich neuroblastoma tumors, which are associated with a favorable outcome, are less vascular. The Cohn lab has determined that the extracellular matrix protein, Secreted Protein Acidic and Rich in Cysteine (SPARC) is a key Schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis. Using mouse models, they have shown that SPARC blocks angiogenesis and impairs neuroblastoma growth. The Cohn lab has also synthesized SPARC peptides that correspond to the epidermal growth factor-like module of the follistatin domain of SPARC and demonstrated that these peptides inhibit neuroblastoma angiogenesis and tumor growth. More recent studies indicate that a SPARC peptide (FSEC) also impairs the growth of pancreatic and lung cancers in preclinical models. Studies focused on investigating the mechanisms by which FSEC inhibits tumor growth are ongoing.
In a second project, the Cohn lab is investigating racial disparities in survival in neuroblastoma. They have recently demonstrated that blacks have a statistically significantly higher prevalence of high-risk disease, increased frequency of late events, and worse outcome than white patients. Although multiple factors contribute to health disparities, their studies indicate that genetic factors play a critical role in the overall poor outcome observed in black children with neuroblastoma. In a collaboration project with Drs. Eileen Dolan and Nancy Cox from the University of Chicago and Dr. John Maris from the Children’s Hospital of Philadelphia, the Cohn lab is elucidating and functionally characterizing the genetic factors that contribute to the poor outcome and chemotherapy resistance observed in black children with neuroblastoma using whole genome data from a 3600 neuroblastoma patient cohort. They are also conducting a second generation GWAS (functional-GWAS; fGWAS) analysis to identify genes associated with outcome within the entire neuroblastoma cohort and the black subset. Understanding the genetic variables that contribute to ethnic diversity in chemotherapy response and outcome in neuroblastoma is critical for the development of more effective, individualized treatment strategies that will maximize response, minimize toxicity, and ultimately, eliminate the current disparities in outcome.