Forskningsområde

Prof. Daniel Ketelhuth's academic career started at the University of São Paulo, where he obtained his Biochemical-Pharmacy degree and a PhD in Immunology. In the next fourteen years, at the Karolinska Institute, Daniel progressed from a postdoc to successfully becoming an independent research leader. Recruited to the University of Southern Denmark in 2019, Prof. Ketelhuth leads a research team of ten members (including PhDs, postdocs, and technicians) and spearheads the Centre for Advanced Cell Analysis, generously supported by a large Novo Nordisk Foundation grant. Throughout his career, he has managed (co-managed) numerous projects/grants, and produced nearly eighty articles, several published in top journals and highly cited. Beyond research, he has also contributed to the academic sphere by mentoring over thirty fellows and contributing to undergrad, master's, and postgraduate programmes across disciplines in Sweden and Denmark.

Forskningsinteresser

Earlier in his career, Prof. Ketelhuth focused his research on identifying and characterizing epitopes from apolipoprotein B-100 (ApoB100)/ low-density lipoprotein (LDL) that could activate the innate and adaptive immune system and drive atherosclerosis. His discovery that LDL oxidation isn't necessary to trigger inflammation and atherosclerosis, which was published in high-impact journals, marked a significant shift in his field (Hermanson & Ketelhuth et al., JEM. 2010 and Ketelhuth et al., Circulation. 2011). These findings led to numerous innovative studies, new research tools, and promising therapeutic targets, including IP for ApoB100 vaccine epitopes (Gistera et al., JIM. 2017) that were licensed to a biotech company for R&D. Transitioning to an independent researcher in the early 2010s, he became a pioneer in immunometabolism in cardiovascular disease (CVD), revealing the atheroprotective role of the kynurenine pathway of tryptophan metabolism (Zhang et al., EHJ. 2012). The initial findings that a tryptophan metabolite, 3-hydroxyanthranilic acid, could regulate vascular inflammation and reduce plasma cholesterol levels spurred multiple studies investigating this metabolite as well as the pathophysiological role of kynurenine pathway enzymes, especially its major rate-limiting indoleamine2,3-dioxygenase-1 (Polyzos et al., Card Res. 2015; Forteza et al., Front Immunol. 2018; Berg et al., Card Res. 2020; Baumgartner et al., JIM. 2021), many collaborations, grants, and a partnership with a pharmaceutical company for drug development based on tryptophan metabolite analogues. More recently, his research has expanded beyond tryptophan, investigating several new immunometabolic targets, and identifying the pyruvate dehydrogenase/pyruvate dehydrogenase kinase axis (PDH/PDK) as a major regulator of CVD¾this work also pinpointed succinate as a key mediator of vascular inflammation and suggested that inhibition of PDK activity could be used to prevent atherosclerosis (Forteza et al., Card Res. 2023).

Main research questions

• Identify and characterize metabolic targets, e.g., enzymes and metabolites, involved in the modulation of vascular inflammation and the development of atherosclerosis and abdominal aortic aneurysms.
• Understand how the dynamics of metabolic dysregulation influence cardiometabolic disease.
• Decipher the complex immunometabolic communications underlying the mechanisms of plaque instability.