Understanding Ubiquitin-dependent Regulation of Iron Metabolism using Mass Spectrometry

NIH RePORTER · NIH · R35 · $393,438 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Iron metabolism is an essential biological pathway that broadly impacts cellular processes ranging from aerobic respiration and nucleic acid metabolism to oxygen transport and multiple biosynthetic pathways (amino acid, nucleotide, and lipid). To maintain sufficient iron to perform these key cellular functions while avoiding the toxicity associated with excess iron, eukaryotic cells have developed an intricate set of regulatory pathways that coordinate iron utilization, transport, and storage and ensure that cellular iron levels are kept under tight physiological control. My laboratory has established a multi-faceted research program that utilizes a combination of biochemistry and proteomic mass spectrometry-based methods to explore the regulatory mechanisms underlying iron metabolism. We are currently focused in two areas. First, we are characterizing the E3 ubiquitin ligase FBXL5 and examining the hypothesis that it functions as a key signaling hub responsible for integrating a diverse set of iron-regulated signaling cues in order to coordinate multiple iron homeostatic pathways. Second, we are actively developing novel proteomic mass spectrometric methods to address key outstanding questions in iron metabolism and other biological processes. Investigation into these areas will not only uncover novel features regulating iron metabolism but also contribute to our understanding of how dysregulation of these pathways contributes to human disease.

Key facts

NIH application ID
10842958
Project number
1R35GM153408-01
Recipient
UNIVERSITY OF CALIFORNIA LOS ANGELES
Principal Investigator
James Akira Wohlschlegel
Activity code
R35
Funding institute
NIH
Fiscal year
2024
Award amount
$393,438
Award type
1
Project period
2024-04-01 → 2029-03-31