Gustavo Luis Tripodi - Postdoctoral Fellowship 2022

Project summary:
Targeting the kynurenine pathway of tryptophan degradation to  combat abdominal aortic aneurysm

The main objective of the present project is to explore the metabolism of tryptophan through the kynurenine pathway in abdominal aortic aneurysms (AAA) in order to identify new therapeutic and diagnostic targets for the disease. In order to reach our goals, the following interconnected aims are proposed

1a) Characterize the kynurenine pathway in human AAA tissue samples

1b) Evaluate the levels of kynurenines in plasma of AAA patients and controls

2) Evaluate the potential of the pharmacological inhibition of the kynurenine pathway enzymes to prevent experimental AAA.

Project Title

Targeting the kynurenine pathway of tryptophan degradation to  combat abdominal aortic aneurysm


Generally asymptomatic, rupture of abdominal aortic aneurysms  (AAA) leads to lethal bleeding and death in 65-85% of cases. While treatment  relies almost exclusively on surgical intervention, proven drugs to prevent AAA  remain absent. Strong evidence indicates that targeting the inflammatory process  driving AAA pathogenesis could be a suitable approach against this disease. Our  group has shown that modulating the kynurenine pathway (KP) of tryptophan  degradation halts vascular inflammation and atherosclerosis. Whether targeting of  the KP can protect against AAA remains unclear.


This project will characterize in depth the KP in AAA, and  explore new potential therapeutic and diagnostic targets against it


In this context,  we will:

  • Access and analyze KP enzymes and metabolites on unique human AAA samples
  • Investigate and detail molecular processes in cell culture systems
  • Test lead KP candidate targets in animal models of AAA

This work carries the  potential to reveal whether the KP enzymes and metabolites can regulate major  inflammatory components in the vascular wall, including activation of the NFκB and  the inflammasome on macrophages, antigen presentation and T cell expansion,  and the deleterious dedifferentiation of vascular SMCs.

Gustavo Luis Tripodi

  • MD and PhD
  • University of Southern Denmark, Institute of Molecular Medicine


Jes Sanddal Lindholt, University of Southern Denmark, Department of Clinical Research

Lars Melholt Rasmussen, Department of Clinical Research, University of Southern Denmark & Head of Research at Dept. of Clinical Biochemistry and Pharmacology, Odense University Hospital

Daniel F. J. Ketelhuth, Professsor, University of Southern Denmark