Our lab uses integrated omics approaches, innovative model systems and CRISPR-based engineering to study how our organs and cells age. The long term goal is to find new ways to extend healthy life span and promote well being of elderly people.

Our three major research lines are:

Mechanisms of Proteostasis Impairment in Aging and Neurodegeneration

The impairment of proteostasis and resulting aggregation of misfolded proteins are associated with age-related diseases such as neurodegenerative disorders and type II diabetes. We focus on (i) how aging perturbs major protein complexes involved in protein synthesis (ribosome) and degradation (proteasome), (ii) how protein localization and post-translational modifications influence protein function in aging, and (iii) the interplay between mutations linked to increase risk of neurodegeneration and the aging process.

Modified from Cellerino and Ori, Sem Dev Cell Biol 2017

Stem cell aging

Adult (somatic) stem cells play a crucial role in maintaining and regenerating organs. However, their function and number decrease during aging. A particular focus of my lab is to understand molecular mechanisms that lead to the loss of these cells’ regenerative capacity. Focusing on the intestinal epithelium and skeletal muscle, we study proteome profiles of stem cells and surrounding tissue across age groups and following injury and evaluates the consequences of anti-aging interventions such as dietary restriction.

Modified from Ermolaeva, Neri, Ori and Rudolph, Nat Rev Mol Cell Biol 2018

Organelle Maintenance During Aging and Disease

Lysosomes plays a central role in autophagy and therefore in protein quality control and aggregate clearance. In addition, lysosomes are involved in intracellular signalling and in regulating cellular physiology in response to changes in nutrient availability via the mTORC1 complex, a key modulator of aging. Together with collaborators from Stanford and MIT, we pursue two major lines of research: (i) charting the composition of lysosomes in different brain cell types and in a model of Batten disease; (ii) studying the impact of aging and anti-aging interventions on the composition of lysosomes across multiple tissues.