Research Area
Aging

Grant Type
Fellowship

Year
2015

Abstract

Degeneration at the cognitive level, known as dementia, is seen in a large proportion of the American population and dementia associated with neurodegenerative diseases exacts a large societal and financial burden. Despite the identification of causal genetic mutations, the mechanisms of neurodegenerative diseases are still poorly understood and complex, impeding the design of therapeutic interventions to treat these disorders. Functional genomic analyses provide a powerful platform to investigate quantitative molecular phenotypes and pathways underlying disease progression in an unbiased, genome-wide manner. In this project, we attempt to understand the complex molecular mechanisms underlying frontotemporal dementia, (FTD), the second most common cause of dementia in the presenile age group (<65 years of age). By leveraging postmortem human and mouse models of disease, we hope to identify core biological processes which are causal to the disease. Our study explores a master regulator of neurodegeneration and we validate its role in degeneration using in vitro and in vivo models of FTD. Finally, we lay framework for future drug discovery using human disease-relevant unbiased transcriptomic networks. Thus, this project significantly broadens our understanding of molecular mechanisms involved in FTD and has opened future avenues for drug discovery to a much wider field of dementia associated with the tau protein.