Call for Research
Mechanism of neuronopthic Gaucher disease

• October 1, 2015
• Limitation – United States Based Researcher/Institution
• Amount – $75,000 to $100,000
• Term – 1 Year (beginning January 1, 2016)
• Review – Proposals will be reviewed beginning December 1, 2015
• Deadline – Deadline for receipt of proposals December 15, 2015
• Format – Maximum 5 pages / PDF / email delivery

Much progress has been made in our understanding of the pathogenesis of neuronopathic Gaucher disease over the past 15 years. Defective calcium homeostasis was first identified in cell and animal models and confirmed in Gaucher patients. We now know that there is regional neuronal loss and inflammation and that cellular glucosylceramide levels do not explain this selective vulnerability. Biochemical pathways have recently been identified which appear to play a crucial role in the evolution of pathological neuroinflammatory changes in affected tissues. These include the RIPK (receptor-interacting protein kinases) pathway, which participates critically in the initiation of necroptotic cell death and neuroinflammation and probably other pathways up – or downstream of RIP.

At this stage of research on this disorder, the CGRF is in search of complementary collaborative research that will examine mechanisms, particularly inflammatory ones, in relevant cellular models of specific patients with various forms of neuronopathic Gaucher disease.

Our goal is to study the molecular mechanisms in human cells, and possible therapeutic avenues, involved in neuroinflammation-induced necroptosis, including RIPK-dependent necroptosis. The successful investigator should have experience with generating neurons and macrophages/microglia, alone and in coculture, from induced pluripotent cells generated from skin fibroblasts of patients with Gaucher disease type 1, type 2 and type 3. With such material, the investigator should also have already identified neuronal Gaucher phenotypes in cultures that are ‘corrected’ with recombinant glucocerebrosidase. Experience in generating mechanistic data on neuronal death and inflammation in Gaucher cellular models is desired. Collaborative research planned with top investigators in the field is critical.

For questions and submission of research proposals contact:

                                Raphael Schiffmann M.D., M.H., Sc.

                                Baylor Research Institute

                                Raphael.schiffmann@baylorhealth.edu / 214-820-4533