MicroRNAs Regulating Diabetes and Obesity

In this Focus Group, Hans Fischer Senior Fellow Prof. Klaus H. Kästner (University of Pennsylvania Perelman School of Medicine) collaborated with Prof. Matthias Tschöp and Dr. Carolin Daniel (Institute for Diabetes and Obesity, Helmholtz Zentrum München) on miRNA-mediated control of T-cell activation in obesity.

Understanding the complex pathology of the metabolic syndrome and the contribution of inflammation are critical to shaping effective preventive and therapeutic measures for obesity and Type 2 Diabetes mellitus (T2DM). Moreover, there is an increasing realization that obesity affects the immune system, promoting inflammation, and potentially leading to a variety of chronic conditions and diseases. Our understanding of the role of individual microRNAs for immune activation vs. regulation is in its infancy, especially in the context of inflammatory states such as obesity and T2DM. We know even less about the critical downstream targets of microRNAs that impact T-cell activation, and thereby impinge on the complex immunological interplay triggering inflammation. Through this project, we will therefore integrate insights in T-cell biology and function with key expertise in metabolism and miRNA-function in T2DM and obesity.

Studies were underway by Verena Ott, PhD. candidate (Daniel lab) in collaboration with Dr. Adam Zahm (Kaestner lab), to identify relevant downstream targets of microRNAs expressed in T-cells. These studies promise to open the path for the development of novel precision medicines synergistically targeting metabolism, immune activation, and inflammation to treat obesity and T2DM.

TUM-IAS funded doctoral candidate:
Verena Ott, Institute for Diabetes and Obesity, HelmholtzZentrum München

Publications by the Focus Group

2018

  • Serr, Isabelle; Scherm, Martin G.; Zahm, Adam M.; Schug, Jonathan; Flynn, Victoria K.; Hippich, Markus; Kälin, Stefanie; Becker, Maike; Achenbach, Peter; Nikolaev, Alexei; Gerlach, Katharina; Liebsch, Nicole; Loretz, Brigitta; Lehr, Claus-Michael; Kirchner, Benedikt; Spornraft, Melanie; Haase, Bettina; Segars, James; Küper, Christoph; Palmisano, Ralf; Waisman, Ari; Willis, Richard A.; Kim, Wan-Uk; Weigmann, Benno; Kaestner, Klaus H.; Ziegler, Anette-Gabriele; Daniel, Carolin: A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes. Science Translational Medicine 10 (422), 2018, eaag1782 mehr…

2017

  • Kälin, Stefanie; Becker, Maike; Ott, Verena B.; Serr, Isabelle; Hosp, Fabian; Mollah, Mohammad M.H.; Keipert, Susanne; Lamp, Daniel; Rohner-Jeanrenaud, Francoise; Flynn, Victoria K.; Scherm, Martin G.; Nascimento, Lucas F.R.; Gerlach, Katharina; Popp, Vanessa; Dietzen, Sarah; Bopp, Tobias; Krishnamurthy, Purna; Kaplan, Mark H.; Serrano, Manuel; Woods, Stephen C.; Tripal, Philipp; Palmisano, Ralf; Jastroch, Martin; Blüher, Matthias; Wolfrum, Christian; Weigmann, Benno; Ziegler, Anette-Gabriele; Mann, Matthias; Tschöp, Matthias H.; Daniel, Carolin: A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function. Cell Metabolism 26 (3), 2017, 475-492.e7 mehr…

2016

  • Serr, Isabelle; Fürst, Rainer W.; Ott, Verena B.; Scherm, Martin G.; Nikolaev, Alexei; Gökmen, Füsun; Kälin, Stefanie; Zillmer, Stephanie; Bunk, Melanie; Weigmann, Benno; Kunschke, Nicole; Loretz, Brigitta; Lehr, Claus-Michael; Kirchner, Benedikt; Haase, Bettina; Pfaffl, Michael; Waisman, Ari; Willis, Richard A.; Ziegler, Anette-G.; Daniel, Carolin: miRNA92a targets KLF2 and the phosphatase PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity. Proceedings of the National Academy of Sciences 113 (43), 2016, E6659-E6668 mehr…
  • Wang, Yue J.; Golson, Maria L.; Schug, Jonathan; Traum, Daniel; Liu, Chengyang; Vivek, Kumar; Dorrell, Craig; Naji, Ali; Powers, Alvin C.; Chang, Kyong-Mi; Grompe, Markus; Kaestner, Klaus H.: Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas. Cell Metabolism 24 (4), 2016, 616-626 mehr…