Nick Urban

Matthias Truttmann Lab
(734) 647-3941

Areas of Interest

Increased caloric intake is associated with various aging-related pathologies, including cardiovascular disease, type II diabetes, cancer, etc. Conversely, caloric restriction—broadly defined as a reduction in caloric intake—has been shown to increase longevity and health span in all organisms tested, ranging from yeast to mammals. However, the mechanisms behind this response are largely unknown.

I am interested in studying the relationship between caloric restriction and AMPylation, a process that involves attaching the post translational modification, adenosine monophosphate (AMP), moiety to exposed serine, threonine, or tyrosine residues. This PTM is conferred by fic-domain containing enzymes (AMPylases; FICD in humans and FIC-1 in C. elegans). Previous literature has shown that the addition of an AMP moiety to molecular chaperone proteins alters their activity, including the ER-resident HSP70 family chaperone BiP. Along with other chaperone proteins, BiP is involved in maintaining cellular proteostasis in part through the Unfolded Protein Response of the Endoplasmic Reticulum (UPR-ER). The inability to mount an effective UPR-ER response correlates with debilitating aging-related pathologies.

Recently, we discovered that the FIC-1 KO C. elegans strain, which has decreased AMPylation levels, enhances caloric-restricted mediated lifespan extensions in C. elegans longevity. However, the molecular mechanism behind this enhancement and the potential effect of loss of AMPylation in mammals remain elusive. Using a variety of genetic and biochemical approaches, as well as our novel mFICD KO mouse model, my focus is on unraveling the relationship between AMPylation and caloric restriction-mediated extension in longevity and health.