Dr. Jan-Wilhelm Kornfeld

Principal Investigator, MPI for Metabolism Research


Dr. Jan-Wilhelm Kornfeld, Dipl.-Biochem.
Principal Investigator, MPI for Metabolism Research
 +49 221 4726 217,-264

Institut für Genetik
Max Planck Institut für neurologische Forschung
Gleuler Str. 50
50931 Köln

Dr. Jan-Wilhelm Kornfeld and his group investigate the role of noncoding RNAs in development and treatment of obesity-associated diseases such as type 2 diabetes. One of the group’s successes has been the identification of a microRNA termed 'miR-802' involved in obesity-associated insulin resistance which represents a novel target structure for the treatment of metabolic disorders in humans.

Our research: In our opinion, one of the biggest scientific discoveries of the last decade was the observation that most genomes within higher organisms are pervasively transcribed into short and long ribonucleic acids (RNA) of which only a  tiny part (<2% of base information) encodes proteins. The >20,000 other, so-called ‘noncoding’ RNAs (ncRNAs), since then emerged as versatile class of regulatory adaptor molecules that control gene expression during embryonic development, tissue specification but also pathophysiological conditions like cancer, diabetes or the ageing process itself. Dr. Jan-Wilhelm Kornfeld and his team at the Max-Planck Institute for Metabolism Research (MPI-MR) aim to identify metabolically acting ncRNAs and interrogate their functional contribution to the establishment and deterioration of obesity-associated neuroendocrine disorders like type 2 diabetes mellitus (T2D).

Our successes: Neurodegenerative diseases such as Alzheimer’s Disease (AD) often coincide in elderly people with metabolic derangements like T2D or the ageing-associated decline in organismal insulin sensitivity. We hypothesized that noncoding RNA-intrinsic signaling cascades could be a common feature shared by both maladies. Indeed, we found that a microRNA termed miR328 functionally silences expression of a key AD gene termed beta secretase (Bace1) in vivo. During both AD cognitive decline, but also obesity-associated metabolic deterioration, miR328 levels plummet and are no longer able to keep Bace1 protein levels at bay. Elevated Bace1 in turn predispose neurons to beta-amyloidosis in the brain and also impair the ability of metabolically active organs like brown adipose tissue to adapt their oxidative phosphorylation potential and concurrently trigger a decrease in systemic energy expenditure. Using small-molecule Bace inhibitors we could reverse the obesity-associated loss of glucose homeostasis and insulin sensitivity and reinstated metabolic eustasis in obese mice, thereby suggesting that anti-Bace1 compounds could be used not only to delay AD pathogenesis but also to treat the concomitant decline in energy metabolism.

Our goals: Using large-scale genome-wide association studies (GWAS), populations geneticists applied linkage analyses to population cohorts to ultimately identify single nucleotide polymorphisms (SNP) predisposing affected individuals for certain disease traits. Interestingly, the majority of disease-associated SNPs reside in those >98% of genomic information not encoding proteins, thus acting either via affecting expression levels of relevant genes (eQTL), via changes to DNA-regulatory elements or by directly altering the function of underlying noncoding RNAs. As sites of noncoding transcription are often ‘hotspots’ of disease-associated SNPs, we hypothesize that the functional contribution of noncoding transcripts in the context of human diseases has hitherto been underestimated. With the advance of novel, sequence-specific and well-tolerated anti-sense RNA inhibitors, we are moving towards clinically-relevant ‘RNA medicine’ against diseases-associated RNAs. The Kornfeld lab strives to take part in this ‘Noncoding Revolution’ by catalogueing and deciphering the molecular properties of microRNAs and long noncoding RNAs (lncRNAs) that are centrally positioned within homeostatic signaling circuits regulating energy homeostasis in health and disease.

Our methods/techniques: Our group applies a broad spectrum of enabling analytical techniques ranging from Next-Generation Sequencing, epigenomic profiling to genome editing approaches in vivo. More recently, we implemented global RNA interactomic techniques like ChIRP and devised novel user-friendly systems -OMICS data integration and visualisation approaches.


Figure 1: Control of glucose metabolism by lncRNAs. Using deep RNA-Seq we identified >40 lncRNAs correlating with obesity and type 2 diabetes (T2D) in mice. Using transgenic models we study the consequence of in vivo lncRNA loss and identify novel lncRNA targets for obesity intervention.

Figure 2: Control of brown adipose tissue (BAT) by microRNAs. Activated BAT controls glucose homeostasis and better understanding BAT function may reveal novel RNA therapeutics for obesity and T2D. We show aging- and obesity-associated loss of BAT function is controlled by a novel microRNA signaling axis that also govern! glucose metabolism in mice.

CECAD Cooperations
EXTERNAL Cooperations
  • Anne Brunet, Stanford University, CA, USA
  • Haiming Cao, NIH Bethesda, MA, USA
  • Thomas de Aguiar Vallim, UC Los Angeles, CA, USA
  • Prof. Dr. Jörg Heeren, UK Hamburg-Eppendorf, DE
  • Christian Helin, BRIC, Copenhagen, DN
  • Prof. Susanne Mandrup, Southern Denmark University, Odense, DN
  • Dr. M. Mori, University of Campesinas (UNICAMP), BR
  • Ulf Ørom, Max Planck Institute for Molecular Genetics, Berlin, DE
  • Camilla Scheele, Rigshospitalet, Copenhagen, DN
  • Dagmar Wachten, caesar Bonn, DE
  • Igor Ulitsky, Weizmann Institute of Science, Rehovot, IL
  • Bernd Wollscheid, ETH Zürich, CH