Research

Proteomics of stem cells aging

Aging is accompanied by a progressive decline of organ function. This contribute to an increased frailty of elderly individuals and represents the major risk factor for many diseases. Adult (somatic) stem cells reside in virtually any organ and play a crucial role in organ maintenance and regeneration in case of injury. In my lab, we are interested to study the molecular mechanisms that lead to reduced stem cell function during aging. To achieve this, we study the proteome of pure populations of stem cells as well as the organ that they reside in (stem cell niche). This strategy allows us to monitor both cell intrinsic as well as extrinsic changes that influence the regenerative capacity of stem cells during aging. We use bioinformatic approaches to integrate different sets of data and identify candidate proteins that we test using functional assays.

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Protein interactions and post-translational modifications in aging

We and others have previously shown that multiple mechanisms can influence the availability of functional proteins during aging. These include changes in protein synthesis, intra-cellular localization and post-translational modifications (Ori, Toyama, et al, Cell Systems 2015). Currently, we apply and develop novel approaches that use mass spectrometry to study protein interactions, stability, organelle composition and different types of post-translation modification in the context of aging.

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Modified from Cellerino and Ori Sem Dev Cell Biol 2017

Comparative analysis of exceptionally short- and long-lived model organisms

By taking advantage of the natural variability in lifespan between species, we aim to identify key determinants of longevity, and bring these in the context of human aging. Thanks to internal and external collaborations, we have access to multiple model organisms ranging from the short-lived fish Nothobranchius furzeri, which has a lifespan of approx. 40 weeks, to the long lived rodent naked mole-rat that can live up to 30 years. The majority of our studies are based on unbiased integrated omics approaches, bioinformatic analysis, and follow up studies in established model organisms of aging.

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