Myeloid cell dysfunction in brain aging and neurodegenerationGlobal transcriptional or epigenetic studies of aging point to major changes in myeloid cell or macrophage function across multiple tissues. We are interested in the basis of this cellular dysfunction and whether reprogramming and rejuvenating this lineage can slow or reverse brain aging and neurodegenerative diseases such as Alzheimer’s, frontotemporal dementia, or ALS.
Proteomics of aging and neurodegeneration
To understand brain aging and neurodegeneration at an organismal level we use focused proteomic screens based on the idea that changes in secreted factors that communicate between cells (the “communicome”), could inform us about the physiological and pathophysiological state of the organism and provide potential new mechanistic insight. Increasingly, we use also unbiased mass spectrometry to study aging, neurodegeneration, and rejuvenation, and we are developing bio-orthogonal tools to label defined subsets of the proteome in vivo.
An organismal approach to understanding brain aging and neurodegeneration
Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. We want to discover such factors, identify their origins, and understand their functions to learn not only about basic mechanisms of aging and neurodegeneration, but also to develop new therapeutic approaches and diagnostic tools for Alzheimer’s and related diseases.