Research Group Gollasch

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Current projects

Figure 1

Our group focuses on ion channels, primarily in vascular smooth muscle cells (VSMC), to clarify mechanisms contributing to hypertension and cardiovascular disease. Potassium channels, chloride channels and transient receptor potential (TRP) channels have received special attention. In collaboration with Björn Schroeder (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)), we investigated the role of smooth muscle TMEM16a chloride channels. We showed that VSMC TMEM16 channels function as regulator of agonist-dependent arterial constriction and systemic blood pressure. In collaboration with Thomas Jentsch and Michael Bader (MDC), we provided definitive evidence that myogenic responses of mouse mesenteric and renal arteries rely on ligand-independent, mechanoactivation of AT1R subtype a. We are currently studying biased agonism and ryanodine receptor isoforms (Figure 1) in VSMC potassium channels gating and myogenic tone.  A particular attention is paid to various KCNQ potassium channel isoforms in periadventitial vasoregulation.  Thomas Jentsch is helping us here. We also have a project focusing on the perivascular adipose tissue (PVAT) as a source for relaxing factors. Here, we collaborate with Wolf-Hagen Schunck (MDC), who has peaked our interests in eicosanoids. We also collaborate with Huang Yu, Hong Kong, China.  Together, we continue to work on the novel concept that perivascular adipose tissue (PVAT) function requires considering heterogeneous PVAT as a specialized organ that can differentially regulate vascular function depending on its anatomical location.   Finally, in collaboration with the German Institute of Human Nutrition (DIfE), we are studying human diabetic nephropathy with a focus on genetics.

TMEM16a and TRP channels

TMEM16a, TRPC6, and TRPV1 channels are expressed in the vasculature. We used smooth muscle specific TMEM16a deficient mice and found that TMEM16a downregulates agonist-induced vasoconstrictions and thereby contributes to blood pressure regulation. Our current research in this area is directed towards identifying role of TMEM16a and ryanodine receptor isoforms in local and global calcium signaling in myogenic arteries and collateral arterial networks. We have also found that TRPV1 and TRPV4 channels play a role in regulating renal blood flow. We found that TRPV1 channels can contribute to ischemia/reperfusion (I/R) -induced kidney injury. In collaboration with Bernd Nürnberg (Tübingen), our current research is directed towards the discovery of novel mechanisms underlying TRPC6 and TRPV4 related kidney pathologies.

Eicosanoids, H2S and Inflammation

EETs serve as endothelial-derived hyperpolarizing factors (EDHF), but may also affect cardiovascular function by anti-inflammatory mechanisms. Our current research in this area is directed towards identifying the role of H2S producing enzymes as regulator of vasodilatory EETs and nitric oxide (NO). In diabetes mellitus, the level of ortho-tyrosine (o-Tyr), an oxidized amino acid is increased.  We found that elevated levels of o-Tyr contribute to vasomotor dysfunction in diabetes mellitus. By an improved tag-switch method, we identified thioredoxin to act as depersulfidase. In collaboration with Ralf Dechend, we also identified a novel role of vitamin D in hypertension and target-organ damage. Our data suggest that even short-term severe vitamin D deficiency may directly promote hypertension and impacts on renin-angiotensin system components that could contribute to target-organ damage and increased cardiovascular risk in ageing.

Vasodilator signals from perivascular adipose tissue

We have identified a vasorelaxing factor produced in the perivascular adipose tissue (ADRF). Our recent work showed that KCNQ channels could represent the subtype of Kv channels involved. The "third gas", namely H2S, could represent ADRF. However, other adipokines may also play a role. We identified alterations in the paracrine control of arterial tone by periadventitial adipose tissue in animal models of hypertension and metabolic disease. KCNQ and cystathionine gamma-lyase deficient mice are available to us to clarify the role of Kv channels and H2S. ADRF and its putative targets (KCNQ channels) might represent exciting new targets for the development of drugs for treatment of cardiovascular and metabolic disorders. Overall, our and other data indicate that dysfunctional perivascular adipose tissue (PVAT) contributes to cardiovascular risk. Our current research is directed towards the discovery of novel mechanisms underlying eicosanoid, H2S and KCNQ related vascular dysfunction.

Genetic renal diseases

An outgrowth of Maik Gollasch’s clinical responsibilities has been a focus on clinical genetics related to renal diseases. We have performed functional analyses of mutations causing familiar kidney diseases with specific emphasis on TRPC6 channels in focal and segmental glomerulosclerosis (FSGS). We identified a unique CD2AP mutation in a German family, supporting the overall concept that CD2AP-associated nephropathy is an autosomal dominant form of FSGS in man.  We are also studying human diabetic nephropathy with a focus on genetics. For these purposes, we established an Outpatient Kidney Clinic at the MDC Campus Berlin Buch (https://www.mdc-berlin.de/8233420/en/research/themes/translation/ecrc, www.hochschulambulanz-charite-buch.de) and the Registry of Diabetic Nephropathy (http://www.charite-buch.de/rdn/). We are continuously recruiting patients for our Registry and renal/vascular disease-specific family studies. Through these studies, we hope to identify novel mechanisms leading to increased cardiovascular risk and target-organ damage and novel treatment targets.

Vasodilator signals from perivascular adipose tissue

We have identified a vasorelaxing factor produced in the perivascular adipose tissue (ADRF). Our recent work showed that KCNQ channels could represent the subtype of Kv channels involved. The "third gas", namely H2S, could represent ADRF. However, other adipokines may also play a role. We identified alterations in the paracrine control of arterial tone by periadventitial adipose tissue in animal models of hypertension and metabolic disease. KCNQ and cystathionine gamma-lyase deficient mice are available to us to clarify the role of Kv channels and H2S. ADRF and its putative targets (KCNQ channels) might represent exciting new targets for the development of drugs for treatment of cardiovascular and metabolic disorders. Overall, our and other data indicate that dysfunctional perivascular adipose tissue (PVAT) contributes to cardiovascular risk. Our current research is directed towards the discovery of novel mechanisms underlying eicosanoid, H2S and KCNQ related vascular dysfunction.

Primary funding

The Deutsche Forschungsgemeinschaft (GO 766/22-1 "Rolle von Ryanodinrezeptor Ca2+ Kanälen bei adaptativen Gefäßprozessen", GO 766/15-2 "ADRF, Gefäßregulation und Hypertonie", GO 766/12-3 "Molekulare Mechanismen der vaskulären Autoregulation", GO 766/18-1 "TRPC6 und Niere"), Deutsche Akademische Austauschdienst (DAAD), Deutsche Zentrum für Herz-Kreislauf-Forschung eV (DZHK), Dr. Werner Jackstädt-Stiftung, and cooperative grants between the MDC and ECRC are funding our work.

Selected publications

1. Tsvetkov D, Tano JY, Kassmann M, Wang N, Schubert R, Gollasch M. The role of DPO-1 and XE991-sensitive potassium channels in perivascular adipose tissue-mediated regulation of vascular tone. Front Physiol. 2016 Aug 4;7:335. doi: 10.3389/fphys.2016.00335. PubMed PMID: 27540364; PubMed Central PMCID: PMC4973012.

2: Riehle M, Büscher AK, Gohlke BO, Kaßmann M, Kolatsi-Joannou M, Bräsen JH, Nagel M, Becker JU, Winyard P, Hoyer PF, Preissner R, Krautwurst D, Gollasch M, Weber S, Harteneck C. TRPC6 G757D Loss-of-function mutation associates with FSGS. J Am Soc Nephrol. 2016 Sep;27(9):2771-83. doi: 10.1681/ASN.2015030318. PubMed PMID: 26892346; PubMed Central PMCID: PMC5004639.

3: Chen L, Kaßmann M, Sendeski M, Tsvetkov D, Marko L, Michalick L, Riehle M, Liedtke WB, Kuebler WM, Harteneck C, Tepel M, Patzak A, Gollasch M. Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature. Acta Physiol (Oxf). 2015 Feb;213(2):481-91. doi: 10.1111/apha.12355. PubMed PMID: 25069877.

4: Schleifenbaum J, Kassmann M, Szijártó IA, Hercule HC, Tano JY, Weinert S, Heidenreich M, Pathan AR, Anistan YM, Alenina N, Rusch NJ, Bader M, Jentsch TJ, Gollasch M. Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries. Circ Res. 2014 Jul 7;115(2):263-72. doi: 10.1161/CIRCRESAHA.115.302882. PubMed PMID: 24838176.

5: Heinze C, Seniuk A, Sokolov MV, Huebner AK, Klementowicz AE, Szijártó IA, Schleifenbaum J, Vitzthum H, Gollasch M, Ehmke H, Schroeder BC, Hübner CA. Disruption of vascular Ca2+-activated chloride currents lowers blood pressure. J Clin Invest. 2014 Feb;124(2):675-86. doi: 10.1172/JCI70025. PubMed PMID: 24401273; PubMed Central PMCID: PMC3904609.

Structure of the group

Group Leader
Univ.-Prof. Dr. med. Dr. rer. nat. Maik Gollasch

Graduate students and clinical fellows
Chen Lan
Sophie Nickel
Xiaoming Lian
Ning Wang
Artur Kuczmanski
Dmitry Tsvetkov (ERA-EDTA and DAAD fellow)
Dr. Marwan Mannaa

Associated scientists
Dr. Mario Kaßmann
Dr. med. István A. Szijártó
Dr. Yulia Komleva (DAAD fellow)
Dr. Jean-Yves Tano (Alexander von Humboldt fellow)

Technical assistant
Yoland-Marie Anistan
Nadine Wittstruck
Kornelia Buttke