Mission of the lab

In our laboratory, we focus on understanding the signaling networks governing nutrient absorption, deposition, and utilization in different cell types.

Perturbations in signaling cascades evoked by nutrient overload, environmental stress, or aging contribute to the dysfunction of multiple organs. This results in a metabolic imbalance in adipose tissue, intestine, skeletal muscles, and liver that can lead to the development of obesity, type 2 diabetes (TD2), non-alcoholic fatty liver disease (NAFLD), or skeletal muscle loss (sarcopenia). We aim to understand complex signaling networks which regulate nutrient absorption, deposition, and utilization in the abovementioned organs. Especially, we focus on the crosstalk between kinase and ubiquitination-dependent signaling cascades. For this purpose, we combine cell biology, biochemical, and omics approaches with mouse genetics. Using high throughput screening we identified a number of novel kinases regulating lipolysis, including ERK3. Moreover, targeted mouse genetics approach allowed us to establish members of the Protein kinase D family as central regulators of adipocytes’, enterocytes’, and hepatocytes’ metabolism. We plan to further investigate the identified pathways putting special emphasis on their impact on the development of metabolic diseases. In parallel, we utilize screening approaches to find other, non-canonical signaling modules (components of the ubiquitin system) regulating metabolism. Finally, our laboratory is implicated in multiple collaborative projects with Polish and international research institutions and companies. One of them resulted recently in the identification of the role of platelets-derived lipids in the regulation of insulin secretion and the development of age-dependent diabetes. We also actively collaborate with industrial partners to develop drugs targeting identified by us pathways. Therefore, by determining essential signaling networks regulating basic metabolic processes our projects will contribute to more targeted pharmacological strategies for the treatment of metabolic diseases such as obesity, T2D, NAFLD, or sarcopenia.

Selected publications

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.