Roman-Ulrich Müller

Department II of Internal Medicine, CMMC

Modulation of Metabolism in Kidney Disease

Aging is associated with profound changes in cellular metabolism and the decline in metabolic fitness results in aging-associated diseases. We study metabolic interventions as strategies to prevent organ failure with a specific focus on kidney diseases.

Research Focus

The kidneys are central targets of aging-associated diseases.

  • On the one hand, aging is associated with a decline in kidney function and an increased susceptibility to acute kidney injury.
     
  • On the other hand, kidney failure is accompanied by a pre-mature aging phenotype and strongly increases the burden of cardiovascular co-morbidities.

Integrity of cellular metabolism in the kidney is a pre-requisite to organ integrity and is affected by aging. Interestingly, interventions that modulate cellular metabolism – e.g., activation of hypoxia signaling or dietary restriction – have shown an amazing potential in protection against kidney failure.

I believe that the extension of human well-being and maintenance of health is a key purpose of research in the life sciences. Closing the gap between basic science and novel strategies in everyday patient care is a major challenge, but also a lot of fun to work on.

Our Goals

Linking RNA biology with the power of model organisms such as C. elegans bears a huge potential to reveal novel approaches for fighting kidney diseases as well as consecutive morbidity and mortality. Unraveling this potential and translating it to clinical use is the lab's declared aim.

C. elegans is one of the key model organisms to study molecular mechanisms regulating longevity and stress resistance. Consequently, a large number of the signal transduction pathways involved in these phenotypes has been identified using the nematode. Work from Dr. Müller and his team was among the first evidence showing that hypoxia-inducible factor signaling is one of these pathways linking stress resistance, longevity, and tumorigenesis even closer to each other. As to non-coding RNAs in the kidney, Prof. Dr. Müller contributed to the very first microRNA expression profiles from different cell types in the kidney. Furthermore, his group published work showing the importance of this RNA species to kidney development and function.

  • We study interventions that increase fitness and resilience by modulation of cellular metabolism with the aim to prevent loss of kidney function and increase the human healthspan. Translational strategies are central to our research including experiments spanning the whole spectrum from the nematode to humans. Specifically, we use C. elegans to screen for interventions that extend lifespan, examine the identified interventions in mouse models of kidney injury and transfer the most potent approaches to clinical trials.
     
  • Considering the major impact of RNA biology on cellular metabolism, RNA-binding proteins and non-coding RNAs are one of our central interests regarding the molecular mechanisms underlying organ protection.

Key Publications


  1. Ripa R, Ballhysa E, Steiner JD, Laboy R, Annibal A, Hochhard N, Latza C, Dolfi L, Calabrese C, Meyer AM, Polidori MC, Müller RU, Antebi A. Refeeding-associated AMPKγ1 complex activity is a hallmark of health and longevity. Nat Aging. 2023 Dec;3(12):1544-1560. doi: 10.1038/s43587-023-00521-y. Epub 2023 Nov 13. PMID: 37957359; PMCID: PMC10724066.
     
  2. Cukoski S, Lindemann CH, Arjune S, Todorova P, Brecht T, Kühn A, Oehm S, Strubl S, Becker I, Kämmerer U, Torres JA, Meyer F, Schömig T, Hokamp NG, Siedek F, Gottschalk I, Benzing T, Schmidt J, Antczak P, Weimbs T, Grundmann F, Müller RU. Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial. Cell Rep Med. 2023 Nov 21;4(11):101283. doi: 10.1016/j.xcrm.2023.101283. Epub 2023 Nov 7. PMID: 37935200; PMCID: PMC10694658.
     
  3. Späth MR, Hoyer-Allo KJR, Seufert L, Höhne M, Lucas C, Bock T, Isermann L, Brodesser S, Lackmann JW, Kiefer K, Koehler FC, Bohl K, Ignarski M, Schiller P, Johnsen M, Kubacki T, Grundmann F, Benzing T, Trifunovic A, Krüger M, Schermer B, Burst V, Müller RU. Organ Protection by Caloric Restriction Depends on Activation of the De Novo NAD+ Synthesis Pathway. J Am Soc Nephrol. 2023 May 1;34(5):772-792. doi: 10.1681/ASN.0000000000000087. Epub 2023 Feb 9. PMID: 36758124; PMCID: PMC10125653.
     
  4. Seufert L, Benzing T, Ignarski M, Müller RU. RNA-binding proteins and their role in kidney disease. Nat Rev Nephrol. 2022 Mar;18(3):153-170. doi: 10.1038/s41581-021-00497-1. Epub 2021 Nov 3. PMID: 34732838.
     
  5. Müller RU, Fabretti F, Zank S, Burst V, Benzing T, Schermer B. The von Hippel Lindau tumor suppressor limits longevity. J Am Soc Nephrol. 2009 Dec;20(12):2513-7. doi: 10.1681/ASN.2009050497. Epub 2009 Sep 24. PMID: 19797165; PMCID: PMC2794223.