Robert Canova Endowed Chair in Inflammation Research
Location: Cleveland Clinic Main Campus
The Paul Fox lab studies IFN-gamma signaling, mechanisms of blood vessel formation and ferroxidases in iron metabolism.
Education & Fellowships
Medical Education - Cornell University
Ithaca, NY USA
Undergraduate - Cornell University
Ithaca, NY USA
Fellowship - Cleveland Clinic
Cleveland, OH USA
We have discovered a novel translational control pathway that selectively regulates inflammatory gene expression in myeloid cells, and may be an endogenous regulator of the duration and magnitude of the inflammatory response. IFN-gamma induces expression of certain pro-inflammatory mRNAs, e.g., vascular endothelial growth factor (VEGF)-A and ceruloplasmin, but synthesis of the proteins is limited by translational silencing. IFN-gamma induces assembly of the 4-protein, IFN-Gamma-Activated Inhibitor of Translation (GAIT) complex, that binds a specific RNA element in the 3’untranslated region of target mRNAs, and inhibits translation. We are investigating the signal transduction pathways that lead to activation of the GAIT system, the mechanisms by which two of the proteins escape their parent complexes, and the in vivo function of the pathway. Also, we are taking a ribonomic approach to elucidate the family of targets silenced by this pathway. In other major projects in the laboratory, we investigate the molecular mechanisms that regulate endothelial cell polarization and movement, a critical and initiating event in the formation of new blood vessels and in repair of injured vessels. We also study the role of ferroxidases in cellular and whole-body iron metabolism, and particularly their role in inflammatory diseases and chronic renal failure.
Ray PS, Jia J, Yao P, Majumder M, Hatzoglou M, Fox PL. A stress-responsive RNA switch regulates VEGFA expression. Nature 457:915-919, 2009.
Yao P, Potdar AA, Arif A, Ray PS, Mukhopadhyay R, Willard B, Xu Y, Yan J, Saidel GM, Fox PL. Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression. Cell 149:88-100, 2012.
Jia J, Arif A, Willard B, Smith J, Stuehr DJ, Hazen SL, Fox PL Protection of extraribosomal RPL13a by GAPDH and dysregulation by S-nitrosylation. Mol Cell 47:656-663, 2012.
Fan Y, Arif A, Gong Y, Jia J, Eswarappa SM, Willard B, Horowitz A, Graham LM, Penn MS, Fox PL. Stimulus-dependent phosphorylation of profilin-1 in angiogenesis. Nat Cell Biol 14:1046-1056, 2012.
Our education and training programs offer hands-on experience at one of the nationʼs top hospitals. Travel, publish in high impact journals and collaborate with investigators to solve real-world biomedical research questions.Learn More
The SPEAR element (sarbecoviral pan-end activating RNA) and the SPEAR-binding complex are crucial to how SARS-CoV-2 infects host cells to cause COVID-19.
Led by Dr. Fox, researchers from Cleveland and Florida will collaborate to investigate if certain regions of SARS-CoV-2 genetic material, called non-coding RNA, can be targeted to treat or prevent COVID-19 infection.