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Deutsch Intern
Rudolf Virchow Center for Experimental Biomedicine

About the Sumara Group

Research

Adaption to changes in nutrient availability is pivotal for survival of living organisms. Specific responses to fasting and feeding in different organs are regulated by a complex array of hormonal cues. Deregulation of nutrient sensing leads to development of metabolic diseases including type 2 diabetes (T2D). We combine genetic and biochemical approaches to understand the complex signaling events occurring in different organs (e.g. liver and adipose tissue) during fasting, feeding and other physiological conditions.

Hormonal Regulation of Metabolism

Adipose tissue and liver are central to the adaptation to both food deprivation and ingestion of food as they can store large quantities of nutrients and release them when needed. In the fed condition insulin stimulates storage of sugars and lipids in liver and triglycerides in adipose tissue.  Upon fasting adipose tissue responds to shortage of nutrients by inducing lipolysis – a process leading to mobilization and release of free fatty acids (FFAs) and glycerol through catabolism of stored triglycerides. Liver catabolizes stored polysaccharides and induces gluconeogenesis (de novo glucose production) from glycerol and other substrates upon nutrient deprivation. Hepatic sugar absorption and utilization decreases, while beta-oxidation of adipose tissue-derived FFAs and production of ketone bodies is induced. Importantly, uncontrolled activation of the fasting response in these organs largely independent of changes in food supply contributes to chronic hyperglycemia and hyperlipidemia, hallmarks of T2D that constitutes a major world-wide health concern.

Recently, we discovered gut-derived serotonin (GDS) as a fundamentally new hormone implicated in regulation of the fasting response in mice. We showed that GDS promotes lipolysis in adipose tissue and gluconeogenesis in liver while it blocks hepatic glucose uptake. Strikingly, inhibition of GDS synthesis was sufficient to ameliorate hyperglycemia and hyperlipidemia in diabetic mice. However, molecular mechanisms mediating GDS action on adipose tissue and liver are unknown. Currently, one important task of our laboratory is to understand these mechanisms using a combination of targeted and unbiased approaches.

Additionally, we are focusing on identification of novel signaling cascades and hormonal cues in regulation of lipolysis in adipose tissue as well as glugoneogensis, FFAs β-oxidation and ketone bodies production in liver using both genetic and unbiased approaches.

Our research group is supported by the Emmy Noether Program of the German Research Foundation.

Selected Publications

Sumara, G., Sumara, O., Kim, J., Karsenty, G. (2012) Gut-derived serotonin is a multifunctional determinant to fasting adaptation. Cell Metabolism, 16(5):588-600.


Sumara, G., Formentini, I., Collins, S., Sumara, I., Windak, R., Bodenmiller, B., Ramracheya, R., Caille, D., Jiang, H., Platt, K.A., Meda, P., Aebersold, R., Rorsman, P., Ricci, R. (2009) Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell 136(2):235-48.

Staff
Rabih El-Merahbi
Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building: Haus D15
Room: 02.009
Manuela Erk
Technische Assistentin
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef- Schneider- Str. 2
97080Würzburg
Deutschland
Building: Haus D15
Till Karwen
Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building: Haus D15
Room: 02.009
Mona Löffler
Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building: Haus D15
Room: 02.009
Angel Loza Valdes
Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building: Haus D15
Alexander Mayer
Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building: Haus D15
Room: 02.009
Dr. Grzegorz Sumara
Gruppenleiter
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str.2
97080Würzburg
Deutschland
Building: Haus D15
Room: 02.007
Jonathan Trujillo
Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building: Haus D15
Room: 02.009
Teaching

Position

Member - Graduate School of Life Sciences
Supervisor - Biomedicine

The current term program can be found here.