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Institute News

August 2022

The Institute of Pharmacology welcomes Marc Torres Pereiro!

In August, Marc Torres Pereiro has started as a PhD student in the group of Thomas Worzfeld. Before, Marc successfully completed his Master thesis at the Stem Cell Institute of the KU Leuven. In this thesis, he had analyzed the differentiation potential of mouse and human dental organoid cultures. In his PhD work, he will now study molecular mechanisms controlling epithelial plasticity in the kidney.

July 2022

Obituary for Prof. Dr. Karl Joachim Netter

Prof. Dr. Karl Joachim Netter was born in Kiel in 1929. He studied medicine at the Universities of Kiel and Freiburg and received his doctorate in Hamburg in 1953. After postdoctoral work with Feodor Lynen, who later won the Nobel Prize, at the Max-Planck-Institute for Cell Chemistry in Munich, at the Pharmacological Institute of the University of Hamburg and at the National Institutes of Health in Bethesda, he became group leader at the Pharmacological Institute of the University of Mainz in 1967. In 1976 he was appointed Director of the Institute of Pharmacology and Toxicology in Marburg, where his scientific interest focused mainly on drug metabolism and the cytochrome P-450 system. He held numerous important positions, e.g. as co-editor of the "Naunyn-Schmiedeberg's Archives of Pharmacology" and editor of the journal "Toxicology", as chairman of the Senate Commission of the German Research Foundation (DFG) for food safety, as President of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT), as well as Vice Dean of the Faculty of Medicine at the University of Marburg. Even after his retirement in 1997, he remained very actively connected to the University, the Medical Faculty and the Pharmacological Institute in Marburg. Together with his wife Prof. Dr. Dr. Petra Netter, he was particularly dedicated to the promotion of young talents and, for example, established the Netter Endowment Fund under the umbrella of the von Behring-Röntgen Foundation, which supports young scientists and international scientific exchange. Prof. Dr. Karl Joachim Netter passed away on July 18th after a short, serious illness. With him, the Pharmacological Institute loses an excellent scientist, sponsor and pioneer for international scientific networking.

Prof. Dr. Karl Joachim Netter

July 2022

Discovery of a new pharmacological target for the treatment of gastric ulcers

Ulcer disease of the stomach and duodenum is a frequent clinical problem with potentially serious complications. A decisive factor in the pathogenesis of peptic ulcers is gastric acid. The secretion of gastric acid is controlled by the hormone gastrin released from gastric G cells. The group of Thomas Worzfeld now identified a signaling pathway, which inhibits gastrin expression on a transcriptional level and thereby limits gastrin release and gastric acid secretion. Moreover, the group could show that this signaling pathway is highly relevant for the pathogenesis of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs), a main risk factor of ulcer disease. Activation of this signaling pathway alleviated peptic ulcer disease in mouse models. This study thereby unravels a new potential approach for the pharmacological treatment of gastric ulcers.

Please click here for further information:

https://www.science.org/doi/10.1126/scitranslmed.abf1922

Rui Xu
Rui Xu

July 2022

Experimental antibodies against osteoporosis and multiple sclerosis

Osteoporosis is a disease of the bone characterized by low bone mass and represents the most common cause for bone fractures among the elderly. Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS). Both diseases are highly prevalent in humans; however, the currently available treatment options are limited. Therefore, new therapeutic approaches are urgently needed. The receptor, Plexin-B1, plays an important role in cell-cell communication in the bone and in inflammatory processes in the CNS. An international team from the Max-Planck-Institute for Heart and Lung Research in Bad Nauheim, the Institute of Pharmacology in Marburg and LifeArc in London has now generated an antibody against Plexin-B1. In preclinical mouse models of postmenopausal osteoporosis and multiple sclerosis, this antibody had beneficial effects on disease progression. This experimental work shows that antibodies against Plexin-B1 could potentially represent a new therapeutic approach against osteoporosis and multiple sclerosis.

Please click here for further information:

https://www.jbc.org/article/S0021-9258(22)00707-4/fulltext

Melanie Vogler
Melanie Vogler

July 2022

Retreat of the Institute of Pharmacology

From July 3rd to 6th, the Institute of Pharmacology went to a retreat at the Marburger Haus in the Kleinwalsertal, Austria. We had exciting days with intense discussions in wonderful surroundings.

Thomas Worzfeld
Thomas Worzfeld

May 2022

EU funding from the REACT-EU program

The currently available treatment options for COVID-19 are limited. The aim of a project at the Institute of Pharmacology is therefore to identify novel therapeutic approaches against COVID-19 through pharmacological inhibition of particular cellular enzymes. The project is funded by the REACT-EU program.

Logo Europäischen Union

February 2022

Ph.D. defense of Luping Zhou

On February 18th, Luping Zhou successfully defended her thesis on kidney repair mechanisms and received her Ph.D..

Congratulations, Luping!

Luping Zhou, Thomas Worzfeld
Luping Zhou, Thomas Worzfeld

January 2022

The Institute of Pharmacology welcomes Ciarán McDonnell !

In January 2022 Ciarán McDonnell started his PhD in the group of Mark Schmitt. He completed his MSc at the National University of Ireland Galway, studying Cellular Manufacturing and Therapy. Here he wrote a thesis on a project for the repurposing of a COPD therapeutic to treat COVID-19 ARDS and co-authored a successful grant application to the Disruptive Technologies Innovation Fund. After this, he worked as a research student in the Royal College of Surgeons in Ireland, studying epigenetic changes in intestinal tissue and its impact on IBD and colorectal cancer. In his doctoral thesis at the Pharmacological Institute, Ciarán will investigate the impact of inflammatory signalling on intestinal cells and how this relates to tissue regeneration and oncogenesis.

Ciarán McDonnell

December 2021

The Institute of Pharmacology welcomes Paola Procopio!

In December, Paola Procopio started as a PhD student in the group of Dr. Schmitt. Paola successfully completed her Masters in Molecular and Cellular Biology and Biomedical Sciences at the University of “Tor Vergata” in Rome in October 2021. As part of her master's thesis, which she carried out at the IRCCS (Scientific Institute for Research, Hospitalization and Healthcare) in Rome, she examined the role of STAT3 signaling in the regulation of autophagy and the regeneration of muscle stem cells. In her doctoral thesis at the Pharmacological Institute, Paola will investigate the contribution of inflammatory signals to the activation of alternative intestinal stem cells during intestinal tissue regeneration.

Paola Procopio

November 2021

The Institute of Pharmacology welcomes Bhargavi Sundaresan!

In November, Bhargavi Sundaresan joined the Rattay Lab as Doctoral Student of Natural Sciences. Bhargavi Sundaresan completed her bachelor's degree in Biotechnology in India and her master's degree in Immunology and Inflammatory Diseases in Scotland. She then gained further practical experience at Queen Elizabeth University Hospital in Glasgow as a laboratory scientist. Bhargavi is particularly interested in immune cell-cell communication and a better understanding of inflammatory diseases and autoimmune responses.

November 2021

Highway to Thymus

New antigen access route to the thymus for central tolerance induction

The thymic self-repertoire for T-cell selection is composed of the endogenous antigen expression in epithelial cells, peripheral antigens through import by migratory dendritic cells (DCs) and diffusion of small blood-borne peptides. In a recent publication, a specialized mechanism was identified, that enables efficient thymic sampling of blood-borne antigenic macro-molecules that are too large to diffuse passively into the thymic parenchyma. In a collaborative effort with researchers from Harvard Medical School (Boston, USA), the Massachusetts General Hospital (Boston, USA), the Weizmann Institute of Science (Rehovot, Israel) and the University of Marburg (Kristin Rattay), we show that a discrete subset of DCs in murine and human thymi are uniquely positioned within the vascular wall of thymic microvessels where they project cellular processes into the bloodstream to capture circulating antigenic material. Hence, this newly identified transendothelial DCs represent a new mechanism by which the thymus can actively acquire blood-borne Ags to induce and maintain immunological tolerance.

Please click here for further information:

https://www.nature.com/articles/s41467-021-26446-x

November 2021

The Institute of Pharmacology welcomes Fatemeh Shirafkan!

In October, Fatemeh Shirafkan joined the Rattay Lab as Doctoral Student of Natural Sciences. Fatemeh Shirafkan did her Bachelor and Master degree in Iran in Cell and Molecular Biology. Afterwards, she worked in a biomedical research laboratory gaining further laboratory experience. Fatemeh is particularly interested in biomedical and molecular biology research questions in the field of immunology and cancer research.

November 2021

Pathomorphological sequence of diabetic nephropathy

The group of Hermann-Josef Gröne and Wilhelm Kriz has defined the essential morphologic features of human diabetic nephropathy by using a large data set of a biopsy bank of nearly 1000 biopsies of diabetic nephropathy. Mesangial matrix expansion which can progress to nodular sclerosis is due to an accumulation of glomerular basement membrane produced by podocytes and endothelial cells. Angiogenesis at the vascular pole and at the circumference of Bowman’s capsule as well as in segmental glomerular scarring is a driving force for the progression of diabetic glomerulosclerosis. Tubular atrophy does occur only in those nephrons which exhibit sclerosis and is not an inherent characteristic of the tubules themselves.

Please click here for further information:

https://doi.org/10.1152/ajprenal.00669.2020

October 2021

Chen Jiang receives the Von Behring-Röntgen Young Talent Award 2021

For his outstanding scientific discoveries in the field of epidermal stem cell biology, Chen Jiang was awarded the Young Talent Award of the von Behring-Röntgen Foundation on October 6th, 2021.

Congratulations, Chen!

https://www.nature.com/articles/s41467-021-21513-9

https://www.br-stiftung.de/foerderung/preise/

September 2021

Glycosphingolipids in epithelial differentiation

The group of Hermann-Josef Gröne has shown that glycosphingolipids which, in conjunction with cholesterol, are the relevant lipids in lipid microdomains of the plasma membrane, are necessary for differentiation and resorptive functions of enterocytes. A deficiency of glycosphingolipids in intestinal enterocytes can significantly slow the development of intestinal adenomata and colon cancer probably by multiple mechanisms amongst which the inhibition of cytokinesis is an important aspect. In the kidney, proximal tubular epithelia resemble enterocytes as they also display a brush border and are active in resorption and secretion of metabolites. A selective lack of glycosphingolipids in proximal tubular epithelium protects against absorption of toxic metabolites and against acute renal failure caused by endogenous proteins (myoglobin) and antibiotics (aminoglycosides).

Please click here for further information:

https://doi.org/10.3390/ijms221910539

May 2021

Nature Review Immunology article published: The inflammatory pathogenesis of colorectal cancer

Inflammation has powerful effects on tumor development and affects all steps of tumorigenesis, from tumor initiation, over tumor progression to metastasis. In our current article we review the different forms of inflammation in colorectal cancer and describe the mechansims through which chronic inflammation can initiate tumorigenesis and through which tumour- elicited and therapy- induced inflammation can promote colorectal cancer. We further specify how tumour cells engage and drive the plasticity of stromal cells in the tumormicroenvironment and how extrinsic factors, such as diet, the microbiota and the mycobiota, contribute to inflammation and tumorigenesis in colorectal cancer. We conclude by providing an outlook of how our understanding of the interplay between inflammatory immune responses and tumorigenesis can be used to develop new prevention and treatment strategies for colorectal cancer.

Please click here for further information:

https://pubmed.ncbi.nlm.nih.gov/33911231/

April 2021

Dr. Kristin Rattay is appointed Professor at the Institute of Pharmacology

The Institute of Pharmacology is happy to have Dr. Kristin Rattay as a new professor since April 1st. Kristin Rattay received her Ph.D. from the German Cancer Research Center and the Heidelberg University in Germany where she worked on the transcriptional mechanisms regulating self-peptide expression in medullary thymic epithelial cells. During her Postdoc at the Harvard Medical School in Boston, USA, she studied the importance of venular endothelial cells and their role as gatekeeper cells regulating thymic tissue homeostasis. Her future research will focus on the cellular and molecular mechanisms of tolerance induction in the thymus, studying cell communication between T cells, thymic epithelial cells and endothelial cells, T cell migration through the stroma and the transcriptional regulation of self-peptide expression in the thymus.

 

 

March 2021

Dr. Mark Schmitt starts new research group on intestinal inflammation and cancer

The Institute of Pharmacology welcomes Dr. Mark Schmitt as a new research group leader. Mark Schmitt studied biology at the Karlsruhe Institute of Technology (KIT), Germany. During his Ph.D. in the lab of Prof. Dr. Véronique Orian-Rousseau at the Institute of Toxicology and Genetics in Karlsruhe, he analyzed the functional role of the stem cell marker CD44 as a feedback regulator for Wnt-signaling and CD44v6 as marker of metastatic cancer cells. He joined then joined the lab of Prof. Dr. Riccardo Fodde at the Erasmus Medical Center in Rotterdam, Netherlands, as a postdoctoral research fellow. There, he investigated the pro-tumorigenic effects of inflammation and diet on the intestinal stem cell niche. Afterwards, he moved to the lab of Prof. Dr. Florian Greten at the Georg-Speyer-Haus, Frankfurt, Germany, to work on intestinal cancer and examine cellular plasticity in colorectal cancer progression and therapy response. Since March 1st, he is now research group leader at the Institute of Pharmacology, where his work will focus on the role of cellular plasticity in intestinal inflammation and inflammation-associated colorectal cancer onset.

 

February 2021

Ph.D. defense of Chen Jiang

On February 23rd, Chen Jiang successfully defended his thesis with the title "The role of B-plexins for mechanochemical control of epidermal stem cell divisions in development and cancer". He received his Ph.D. with the best possible grade "summa cum laude".

January 2021

Elucidation of a mechanochemical mechanism to control epidermal stem cell divisions

The precise spatiotemporal control of cell proliferation is key to the morphogenesis of epithelial tissues. Epithelial cell divisions lead to tissue crowding and local changes in force distribution, which in turn suppress the rate of cell divisions. The molecular mechanisms underlying this mechanical feedback are largely unclear. Chen Jiang, PhD student at the institute, and co-workers from Helsinki (Finland), London (UK), Bethesda (USA), Göttingen (Germany), Cologne (Germany) and Bad Nauheim (Germany) have now identified a critical requirement of B-plexin transmembrane receptors in the response to crowding-induced mechanical forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail to sense mechanical compression, resulting in disinhibition of cell divisions and tissue overgrowth. Our work provides evidence that the B-plexin-dependent mechanochemical feedback is also pathophysiologically relevant to limit tumor growth in basal cell carcinoma, the most common type of skin cancer. Our results uncover a central role of B-plexins in mechanosensation to couple cell density and cell division in development and disease.

Please click here for further information:

Photo: Chen Jiang

January 2021

A role for microtubule tyrosination in epithelial morphogenesis

Microtubules form part of the cytoskeleton, and are made up by polymers of tubulin. Tubulin can undergo a post-translational modification called tyrosination. This tyrosination is carried out by the enzyme, tubulin tyrosine ligase (TTL), which adds tyrosine to the carboxy terminus of detyrosinated alpha-tubulin. A research team of the University of Marburg, including Florian Hub and Thomas Worzfeld, has now discovered that the equilibrium between microtubules enriched in detyrosinated or tyrosinated tubulin plays an important role in epithelial morphogenesis.

Please click here for further information

March 2020

TRPC1 modifies cation currents in hippocampal CA1 neurons

TRPC channel subunits (TRPC1-7) form receptor-operated cation channels. Whether TRPC1 can form channels on its own remains unclear, but TRPC1 can heteromultimerize with other TRPCs leading to changes in their functional properties. During her PhD work at the institute, Frauke Kepura (now Dormann) studied the effect of genetic deletion of TRPC1 on receptor-operated cation currents in hippocampal CA1 pyramidal neurons. Cation currents activated downstream of metabotropic glutamate receptors were modified such that inward currents were larger in TRPC1-/- neurons than in TRPC1+/+ neurones. The results indicate that TRPC1 has an inhibitory modulatory effect on cation currents (probably in heteromultimeric complexes with TRPC4 and TRPC5 with which it combines and which are co-expressed in these neurons) and probably does not form homomeric channels. Expression of TRPC1 reduces the tendency of these neurons to generate longer-lasting plateau potentials.

Photo: Tim Plant

Please click here for further information.

March 2020

Gangliosides Modulate Insulin Secretion by Pancreatic Beta-Cells

Type 2 diabetes is an extremely prevalent metabolic disease characterized by high blood sugar levels and relative lack of insulin. The research group of Hermann-Josef Gröne has discovered that negatively charged sialic acid containing ganliosides are synthesized in pancreatic islets at high concentrations. These gangliosides GM3 and GD3 could increase glucose uptake by the glucose transporter GLUT2 in beta cells of pancreatic islets, leading to an increase in insulin secretion; the effect was pronounced under a high glucose load and hyperlipidemia, two conditions found in type 2 diabetes.

For further reading, please click here.

March 2020

Carsten Höß receives the Young Investigator Award of the German Society of Pharmacology and Toxicology

The 86th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) was held from March 2nd to 5th in Leipzig, Germany. Carsten Höß, PhD student at the institute, gave a superb talk on his newly discovered mechanism of plexin signal transduction, and was awarded the "Young Investigator Award" of the Society.

Congratulations, Carsten!

December 2019

Christmas Party

On December 17th, we had the Christmas Party of the Biochemical-Pharmacological Center. All institutes of the Center, i.e. the Institute of Pharmacology and the Institute of Physiological Chemistry of the Medical Faculty and the Institute of Pharmacology and Clinical Pharmacy of the Pharmacy Faculty, enjoyed a wonderful relaxed evening together, with great food and drinks, nice conversations, playing games together and dancing in the disco area!

Photo: Thomas Worzfeld

November 2019

New Research Training Group „The inflammatory tumor secretome – from understanding to novel therapies”

The German Research Foundation has approved 3.9 Million Euro of funding for the years 2020 to 2024 for a Research Training Group in Marburg and Giessen in the field of cancer research. This graduate school will focus on the role of the inflammation-driven tumor secretome for tumor progression and therapy resistance. The consortium will benefit from its interdisciplinary composition represented by basic researchers and clinicians who tackle the competitive field of the tumor secretome by analyzing different tumor entities, i.e. ovarian cancer, prancreatic ductal adenocarcinoma and acute myeloid leukemia.

The Institute of Pharmacology is proud to be part of this consortium with a project on the “Influence of tumor-host secretome on ovarian cancer cell invasion and metastasis”.

For further information, please click here

August 2019

Identification of dickkopf-3 as a novel predictive marker for acute kidney injury

Acute kidney injury (AKI) is the most frequent complication in patients who have cardiac surgery. However, preoperative diagnostic markers for the identification of patients at high risk for postoperative loss of kidney function are missing. Hermann-Josef Gröne now contributed to a study published in “Lancet”, which shows that preoperative urinary dickkopf-3, a modulator of the Wnt/β-catenin signaling pathway, is an independent predictor for postoperative AKI. This could allow preventive strategies in patients at high risk for AKI.

https://www.ncbi.nlm.nih.gov/pubmed/31202596

June 2019

Institute summer party 2019

Foto: Thomas Worzfeld

After a fascinating guided tour through the beautiful Marburg castle, we enjoyed the wonderful weather with barbecue and beer. Cheers!

June 2019

Glycosphingolipids as novel pharmacological targets in acute kidney injury

A new publication of the research team of Hermann-Josef Gröne shows that globotriaosylceramide (Gb3/CD77), a glycosphingolipid expressed in tubular epithelial cells of the kidney, could be a potential new pharmacological target in the treatment of acute kidney injury.

further information

May 2019

Frank Czubayko and Thomas Worzfeld receive the Award for Excellent Teaching of the State of Hesse

Foto: Nadja Düvelmeyer
from left to right - Nora Jochens, Department of Surgery; Dr. Andreas Jerrentrup, Department of Emergency Medicine; Dr. Martin Sassen, Department of Emergency Medicine; Prof. Frank Czubayko, Institute of Pharmacology; Angela Dorn, Minister of Science and Art of the State of Hesse; Prof. Thomas Worzfeld, Institute of Pharmacology; Prof. Katharina Krause, President of the University of Marburg; Prof. Stefan Bösner, Department of General Medicine; Prof. Hinnerk Wulf; Department of Anesthesiology; Dr. Egbert Opitz, Manager of the Patient Safety Teaching Programme

The Award for Excellent Teaching of the State of Hesse 2019 goes to the teaching project “Decide wisely – treat safely” of the University of Marburg. As part of a team of 22 members of the Medical Faculty, Frank Czubayko and Thomas Worzfeld received the award on May 16th 2019 from Angela Dorn, the Minister of Science and Art of the State of Hesse.

Video presentation of the laureates

Information from the Ministry of Science and Art of the State of Hesse (HMWK)

May 2019

Retreat at the Castle Rauischholzhausen

Foto: Hana Sustovà

On May 16th and 17th, we had a joint retreat of the Biochemical-Pharmacological Center and the Marburg Graduate School on “Membrane Plasticity” at the picturesque Castle Rauischholzhausen. 11 research groups of the Faculties of Medicine, Pharmacy and Biology of the University of Marburg spent two fascinating days with great talks and intense and fruitful discussions. An exciting collaborative meeting, made possible by the generous funding of the UMR 2027 initiative of Marburg University!

May 2019

Defense Laura Soto Hinojosa

Foto: Sylvia Krippner

On Tuesday, May 14th, 2019, Laura Soto Hinojosa successfully defended her thesis with the title „MRTF/SRF-dependent transcriptional regulation for bleb-associated cell invasion and entosis”.

Congratulations, Laura, and all the best for your future research as Postdoc at the Centre for Genomic Regulation (CRG) in Barcelona!

February 2019

Tumor-associated macrophages play an important role for the synthesis of lysophosphatidic acid (LPA) in the ovarian cancer tumor microenvironment

A research team of the University of Marburg and the Max-Planck-Institute for Heart and Lung Research, including Dominique Brandt, Robert Grosse and Thomas Worzfeld, discovered that the concentrations of lysophosphatidic acid (LPA) in the ascites of ovarian cancer patients are strongly elevated. This correlates with patient survival. Further analyses showed that tumor-associated macrophages crucially contribute to lysophosphatidic acid (LPA) synthesis.

https://www.ncbi.nlm.nih.gov/pubmed/30353652

https://www.ovara.net/publications

January 2019

New Year's Party 2019

Foto: Christine

On January, 20th, 2019, the Institute of Pharmacology celebrated the arrival of the New Year.

A happy and successful 2019 to everyone!