Metabolic Receptology in the Schwartz Group

The aim of the Schwartz Group is to understand the structural and functional basis for how signaling metabolites and their specific GPCR sensors control endocrine, metabolic and immune functions as the basis for developing novel means to prevent and treat obesity, diabetes and cancer.

Group photo of the Schwartz Group
From left to right: Barbara Thaysen, Simone Jensen, Jesse Arnold Buijink, Isis Paham Abiguime, Hannah Zakariassen, Mette Trauelsen, Thue Schwartz, Stine Lindberg Vedersø, Sally Winther, Jacob Emil Petersen, Oksana Dmytriyeva, Siv Hjorth, Emilie Christensen, xx, Nataliia Tiutcheva, Marianne Gregers, Elizabeth Laura Lansbury, Mette Simons, Salim Hanna

 

 

 

Key metabolites generated from dietary nutrients, gut microbiota and intermediary metabolism function as extracellular messengers that are recognized by and signal through specific GPCRs in a similar manner as hormones and neurotransmitters. The metabolite GPCRs are particularly highly expressed and regulated in endocrine and metabolic cells – in particular adipocytes – as well as immune cells. The overarching hypothesis of the Schwartz Group is that metabolites such as succinate, lactate, ketones and acetate function as acute, auto- and paracrine signals of fuel availability and metabolic stress which are vital for enforcing metabolic homeostasis. However, these protective GPCR-mediated mechanisms can turn into damaging, disease-promoting inflammatory mechanism if the metabolite signaling becomes chronic or systemic and they are responsible for e.g. the survival and growth of cancer cells through metabolic reprogramming and immune evasion.

The group has a strong background in molecular pharmacology and structure-based drug discovery – in close collaboration with Thomas Frimurer – and a major strength is therefore the ability to combine powerful genetic models - often in collaboration with Zach Gerhart-Hines – with a large armamentarium of often unique proprietary pharmacological tools.

 

 

 

 

 

 

Extracellular Succinate Hyperpolarizes M2 Macrophages through SUCNR1/GPR91-Mediated Gq Signaling.

In this 2021 Cell Reports article we describe how physiological concentrations of succinate, a signal of metabolic stress, through SUCNR1 signaling upregulate the anti-inflammatory gene repertoire of M2 macrophages. This protective paracrine mechanism can become pro-inflammatory and cause NAFLD, diabetic retinopathy etc.

Autocrine negative feedback regulation of lipolysis through sensing of NEFAs by FFAR4/GPR120 in WAT. 

In this 2020 Molecular Metabolism paper we identify FFAR4 sensing of NEFAs as being responsible for a classical autocrine inhibitory feed-back loop controlling lipolysis in adipocytes and its potential co-action with multiple other GPCR-driven metabolite sensing autocrine mechanisms. 

L-Cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling

In this 2020 Diabetes paper we describe how the number and secretory capacity of L-cells can be increased to mimic effects of bariatric surgery by nutrient-derived metabolites and their GPCR sensors through a two-armed, serial paracrine mechanism involving GLP-1 stimulation of 5-HT secretion from neighboring enterochromaffin cells and 5-HT stimulation of HTR4 receptors on progenitor cells. This surprisingly identifies HTR4 as a target to control the secretory capacity of endogenous GLP-1 for treatment of diabetes and obesity.  

The lactate receptor GPR81 is responsible for metabolic reprogramming and immune evasion of cancer cells in solid tumors. 

Innovation is a major force of the group. Together with Thomas Frimurer’s group we have developed first-in-class antagonists for GPR81 and – strongly supported by InnovationsFonden, NNF and BioInnnovation Institute (BII) – furthermore in the process of spinning out a biotech company, Warburg. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Group Leader

Thue W. Schwartz
Professor

Phone: +45 2262 2225
tws@sund.ku.dk

Twitter:
Thue W Schwartz (@Thue_Schwartz)

Thue W. Schwartz

Staff list

Name Title Phone E-mail
Abiguime, Isis Paham Master Student   E-mail
Andersen, Maj Fugl Master Student   E-mail
Christensen, Emilie Nellemose Research Assistant   E-mail
Dmytriyeva, Oksana Research Consultant +4522467135 E-mail
Hjorth, Siv Annegrethe Visiting Associate Professor +4535334877 E-mail
Husted, Anna Sofie Postdoc +4535337006 E-mail
Iliyaz, Aslihan Shenol PhD Student +4535332992 E-mail
Imig, Cordelia Guest Researcher +4560904855 E-mail
Jensen, Simone Master Student   E-mail
Johansen, Marianne Gregers Laboratory Technician. +4535334413 E-mail
Krusholt, Luna Li Laboratory Technician +4535324848 E-mail
Lansbury, Elizabeth Laura Research Assistant   E-mail
Larsen, Kathrine Lundø PhD Student +4535331870 E-mail
Mamedova, Esmira External, Ph.d Student   E-mail
Pankratova, Stanislava Affiliate Associate Professor +4535335256 E-mail
Pedersen, Maria Hauge External Researcher   E-mail
Pedersen, Stine Helene Falsig External +4535321546
Petersen, Jacob Emil PhD Fellow   E-mail
Romeral Buzón, Alejandro Master Student   E-mail
Rudenko, Olga Research Consultant +4535327342 E-mail
Schwartz, Thue W. Professor +4522622225 E-mail
Simons, Mette Head Bioanalyst +4528757346 E-mail
Thaysen, Barbara Laboratory Technician +4535321429 E-mail
Tiutcheva, Nataliia Laboratory Technician +4535328126 E-mail
Trauelsen, Mette Postdoc +4535337775 E-mail
Vana, Vasiliki Postdoc   E-mail
Vedersø, Stine Lindberg Laboratory Technician. +4535337528 E-mail
Winther, Sally Postdoc +4535322738 E-mail
Zakariassen, Hannah Louise External Postdoc +4535333846