About the lab
Dioscuri Centre for Metabolic Diseases
Dioscuri (Dioscuri Centres of Scientific Excellence) is a programme initiated by the Max Planck Society, jointly managed with the National Science Centre in Poland, and mutually funded by the Polish Ministry of Education and Science (MEiN) and the German Federal Ministry of Education and Research (BMBF) .
Our Dioscuri Centre for Metabolic Diseases focuses on the elucidation of signaling pathways that play a role in metabolic diseases like type 2 diabetes or cancer associated cachexia.
Mission of the lab
Our lab focuses on the elucidation of signalling pathways that play a role in metabolic diseases.
Perturbations in signaling cascades regulating basic metabolic processes of adipose tissue, intestine and liver often result in metabolic diseases. Excessive absorption of lipids in intestines promotes adiposity. Elevated lipogenesis and lipolysis in combination with reduced energy dissipation are the hallmarks of obesity and type 2 diabetes (T2D). Increased lipogenesis also contributes to the development of liver steatosis. Conversely, induction of negative energy balance during cancer-associated cachexia (CAC) is partially caused by increased metabolic activity of adipocytes. In my research group we aim at understanding of the complex signaling network regulating the above-mentioned basic metabolic processes. For this purpose we combine cell biology, biochemical and omics approaches with mouse genetics. Using high throughput siRNA-based screening we identified a number of novel kinases regulating lipolysis, including ERK3. Targeted mouse genetics approach let us to establish members of Protein kinase D family as central regulators of adipocytes, enterocytes and hepatocytes metabolism. We plan to further investigate the identified pathways and, in parallel, to utilize screening approaches to find other, noncanonical signaling modules (components of the ubiquitin system) regulating metabolism. By determining essential signaling networks this project will contribute to more targeted pharmacological strategies for treatment of metabolic diseases such as obesity, T2D and CAC.
Selected publications
Karwen T, Kolczynska-Matysiak K, Gross C, Löffler MC, Friedrich M, Loza-Valdes A, Schmitz W, Wit M, Dziaczkowski F, Belykh A, Trujillo-Viera J, El-Merahbi R, Deppermann C, Nawaz S, Hastoy B, Demczuk A, Erk M, Wieckowski MR, Rorsman P, Heinze KG, Stegner D, Nieswandt B, Sumara G. Platelet-derived lipids promote insulin secretion of pancreatic β cells. EMBO Mol Med. 2023 Jul 25:e16858.
Wit M, Trujillo-Viera J, Strohmeyer A, Klingenspor M, Hankir M, Sumara G. When fat meets the gut—focus on intestinal lipid handling in metabolic health and disease. EMBO Mol Med. 2022 Apr 19;e14742.
Trujillo-Viera J, El-Merahbi R, Schmidt V, Karwen T, Loza-Valdes A, Strohmeyer A, Reuter S, Noh M, Wit M, Hawro I, Mocek S, Fey C, Mayer AE, Löffler MC, Wilhelmi I, Metzger M, Ishikawa E, Yamasaki S, Rau M, Geier A, Hankir M, Seyfried F, Klingenspor M, Sumara G. Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity. EMBO Mol Med . 2021 May 7;13(5):e13548.
El-Merahbi R, Viera JT, Valdes AL, Kolczynska K, Reuter S, Löffler MC, Erk M, Ade CP, Karwen T, Mayer AE, Eilers M, Sumara G. The adrenergic-induced ERK3 pathway drives lipolysis and suppresses energy dissipation. Genes Dev. 2020 Apr 1;34(7-8):495-510.
Mayer AE, Löffler MC, Loza Valdés AE, Schmitz W, El-Merahbi R, Viera JT, Erk M, Zhang T, Braun U, Heikenwalder M, Leitges M, Schulze A, Sumara G. The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling. Sci Signal. 2019 Aug 6;12(593):eaav9150.
Löffler MC, Mayer AE, Trujillo Viera J, Loza Valdes A, El-Merahbi R, Ade CP, Karwen T, Schmitz W, Slotta A, Erk M, Janaki-Raman S, Matesanz N, Torres J, Marcos M, Sabio G, Eilers M, Schulze A and Sumara G. Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity. EMBO J. 2018 Nov 15;37(22):e99182.
Sumara G, Sumara O, Kim J, Karsenty G. Gut-derived serotonin is a multifunctional determinant to fasting adaptation. Cell Metab. 2012 Nov 7;16(5):588-600.
Oury F*, Sumara G*, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P, Karsenty G. Endocrine Regulation of Male Fertility by the Skeleton. Cell. 2011 Mar 4;144(5):796-809.
Sumara G, Formentini I, Collins S, Sumara I, Windak R, Bodenmiller B, Ramracheya R, Caille D, Jiang H, Platt KA, Meda P, Aebersold R, Rorsman P, Ricci R. Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell. 2009 Jan 23;136(2):235-48.