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In preclinical as well as in clinical studies Ulrich Dirnagl’s research has revealed pathobiology which impact on the outcome after a stroke. Several of these mechanisms can be therapeutically targeted, clinical trials are under way. In addition, through meta-research he was able to identify opportunities for improving research practice and to obtain evidence for the impact of interventions targeted to increase the value of biomedical research. At the Charité Universitätsmedizin Berlin Ulrich Dirnagl is a Professor of Clinical Neuroscience and is the head of the research group Dirnagl at the Department of Experimental Neurology. Since 2017 he is also the founding director of the QUEST Center for Responsible Biomedical Research at the Berlin Institute of Health. QUEST aims at overcoming the roadblocks in translational medicine by increasing the value and impact of biomedical research through maximizing the quality, reproducibility, generalizability, and validity of research.
Introduction to the EQIPD quality system.
Bespalov A, Bernard R, Gilis A, Gerlach B, Guillén J, Castagné V, Lefevre IA, Ducrey F, Monk L, Bongiovanni S, Altevogt B, Arroyo-Araujo M, Bikovski L, de Bruin N, Castaños-Vélez E, Dityatev A, Emmerich CH, Fares R, Ferland-Beckham C, Froger-Colléaux C, Gailus-Durner V, Hölter SM, Hofmann MC, Kabitzke P, Kas MJ, Kurreck C, Moser P, Pietraszek M, Popik P, Potschka H, Prado Montes de Oca E, Restivo L, Riedel G, Ritskes-Hoitinga M, Samardzic J, Schunn M, Stöger C, Voikar V, Vollert J, Wever KE, Wuyts K, MacLeod MR, Dirnagl U, Steckler T.
Elife. 2021 May 24;10:e63294. doi: 10.7554/eLife.63294.
PMID: 34028353; PMCID: PMC8184207.
Improving preclinical studies through replications.
Drude NI, Martinez Gamboa L, Danziger M, Dirnagl U, Toelch U
Elife. 2021 Jan 12;10:e62101. doi: 10.7554/eLife.62101.
PMID: 33432925; PMCID: PMC7817176.
Improving target assessment in biomedical research: the GOT-IT recommendations.
Emmerich CH, Gamboa LM, Hofmann MCJ, Bonin-Andresen M, Arbach O, Schendel P, Gerlach B, Hempel K, Bespalov A, Dirnagl U, Parnham MJ.
Nat Rev Drug Discov. 2021 Jan;20(1):64-81. doi: 10.1038/s41573-020-0087-3. Epub 2020 Nov 16.
PMID: 33199880; PMCID: PMC7667479.
The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.
Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Würbel H.
PLoS Biol. 2020 Jul 14;18(7):e3000410. doi: 10.1371/journal.pbio.3000410.
PMID: 32663219; PMCID: PMC7360023.
Resolving the Tension Between Exploration and Confirmation in Preclinical Biomedical Research.
Handb Exp Pharmacol. 2020;257:71-79. doi: 10.1007/164_2019_278.
Improving the trustworthiness, usefulness, and ethics of biomedical research through an innovative and comprehensive institutional initiative.
Strech D, Weissgerber T, Dirnagl U; QUEST Group.
PLoS Biol. 2020 Feb 11;18(2):e3000576. doi: 10.1371/journal.pbio.3000576.
PMID: 32045410; PMCID: PMC7012388.
Exact replication: Foundation of science or game of chance?
Piper SK, Grittner U, Rex A, Riedel N, Fischer F, Nadon R, Siegerink B, Dirnagl U.
PLoS Biol. 2019 Apr 9;17(4):e3000188. doi: 10.1371/journal.pbio.3000188.
PMID: 30964856; PMCID: PMC6456162.
- Physiology and pathophysiology of cerebral blood flow and metabolism
- Cerebral ischemia and endogenous neuroprotection
- Brain inflammation and brain-immune interaction
- Interaction of brain and body after stroke (metabolism, gut microbiome, etc.)
- Brain imaging (Optical, MR, nuclear medicine)
- Systematic reviews, biostatistics, and quality control in experimental medicine
Most important projects
PREMIER (Predictiveness and Robustness through Modular Improvement of Experimental Research)
"PREMIER" provides the scientific community with structured quality assurance. It consists of modular quality elements that assist researchers in their quest for high-quality preclinical research without stifling their creativity and draining too much resources. "PREMIER" is an Open Source Tool.
More information/project description
BIH-QUEST Center for Responsible Research
The QUEST Center develops and implements new approaches to ensure the trustworthiness, usefulness, and ethics of biomedical research.
More information/project description
"SPF Husbandry as a Challenge to External and Construct Validity in Preclinical Neuroscience Research" (together with Prof. Dr. Christoph Harms, project funded by Excellence Cluster Neurocure)
We posit that raising mice under clean (SPF) conditions is an important reason for translational failure, as they never develop mature immune systems even during aging. We speculate that vascular and neuronal remodelling after stroke in conventional SPF mice is heavily biased by the absence of natural host-microbiota and pathogen interactions and thus mature immune systems, thereby causing the high degree of discrepancy in outcomes between humans and SPF rodents. In this project we are characterizing the pathophysiology of damage and recovery after experimental stroke in mice with mature immune systems.
Rosshart, S.P. et al.
Science 2019 ;365(6452):eaaw4361. doi: 10.1126/science.aaw4361)
Uli Dirnagl's "Science Blog" covers topics related to his research, with a special focus on biostatistics, translational research, publishing, and quality aspects of the biomedical research enterprise.