Scientific Research Institutes > University Institutes > Institute of Pharmacy

Institute of Pharmacy

Director: Univ.-Prof. Dr. Johanna Pachmayr

The Institute of Pharmacy was established in 2017 and is composed of the following departments: Clinical Pharmacy, Pharmaceutical Biology, Pharmaceutical and Medical Chemistry as well as the department for Pharmaceutical Technology and Biopharmaceutics which will be established in the coming year.

The institute focuses its research on the development and testing of agents, the characterisation of new target structures for pharmaceuticals as well as on analysis and biological analysis.

Apart from various research projects the institute also covers the majority of the teachings at the Department of Pharmacy. The aim is to train competent pharmacists that are well prepared for market requirements, pharmaceutical practice and research.

Departments

Pharmaceutical Biology and Clinical Pharmacy

The Department of Pharmaceutical Biology and Clinical Pharmacy is run by Professor Johanna Pachmayr. It focuses on pharmacological testing of new biogenic and synthetic pharmaceuticals and the characterisation of new target structures for drugs which will be advanced towards pharmaco-economic aspects and the evaluation and optimisation of the pharmacotherapy for specific patient groups.

Pharmaceutical and Medicinal Chemistry

The Department of Pharmaceutical and Medicinal Chemistry trains pharmacy students in modern computer-assisted methods of molecular drug design. The research is devoted to the development of modeling methods, to database mining for lead structure search and to the generation of pharmacophore models for the design of new bio-active compounds.

Pharmaceutical Technology and Biopharmaceutics

The Department of Pharmaceutical Technology and Biopharmaceutics will focus on drug delivery and drug targeting, new carrier systems and materials, tissue engineering as well as pharmacokinetic and prediction models.

Research projects

Pharmaceutical Biology and Clinical Pharmacy

As second most cause of mortality worldwide, cancer represents a major health problem. Incidence is increasing and therapeutic options are limited due to resistance. The department of Pharmaceutical Biology and Clinical Pharmacy addresses this problem: we characterize new targets and investigate the pharmacological effects and underlying mechanism of new compounds for cancer therapy.

Cancer therapy with Cdk5-inhibition

Cyclin-dependent kinase 5 (Cdk5) represents a highly interesting target for tumor therapy. Cdk5 was discovered in 1990 and was presumed to be neuron-specific due to ist important function in the central nervous system (CNS). Cdk5 regulates neuronal development and functions like axon guidance or synaptic transmission, and is involved in the pathogenesis of Alzheimer’s and Parkinson’s disease. However, during recent years, extra-neuronal functions of Cdk5 have been discovered. We elucidated crucial functions of Cdk5 in the vascular system: Cdk5 is essential for lymphatic vessel development – genetic knockdown of endothelial Cdk5 results in embryonic lethality, as well as for tumor angiogenesis – inhibition of endothelial Cdk5 impairs tumor growth.

Liver cancer (hepatocellular carcinoma, HCC) is among the most prevalent cancer entities and is characterized by high mortality and increasing incidence. During early stage HCC, therapeutic options include liver transplantation, resection of the tumor, or transarterial chemoembolization (TACE). However, HCC is mostly diagnosed at an advanced stage when therapeutic options are strongly limited as HCC is an extremely chemoresistant cancer. The only approved first-line treatment for advanced stage HCC is the orally available multikinase inhibitor sorafenib. However, patient prognosis is poor – Sorafenib prolongs survival for about three months and shows a response rate of only 2%. New therapeutic options have failed so far. We investigate Cdk5 as novel promising target for HCC therapy.

 

Image 1 – Goal of the combination of Cdk5 inhibition and sorafenib in HCC therapy.

 

 

Sorafenib resistance as a limiting factor in HCC therapy

Despite intensive research during the last decade sorafenib, a multikinase inhibitor, is still the only approved primary therapy for late stage HCC patients. The therapeutic success is strongly influenced in a negative way through possible resistance development and side effects. These side effects can force a therapy break or make it necessary to stop the therapy entirely. Therefore, it is vitally important to uncover the molecular mechanisms behind resistance development and thus improve the therapy situation of HCC patients. For that purpose, we generated sorafenib resistant HDD cells (image 2) to examine the underlying resistance mechanisms. The results of these exams will be used to develop new therapy strategies and circumvent resistance development.

 

 

 

 

Image 2 – Through the development of resistance induced changes of the HCC cells' morphology (wildtyp HUH7 (HUH7-WT): left; sorafenib-reistent HUH7 (HUH7-R): right)

 

Pharmaceutical and Medicinal Chemistry

How save are environmental chemicals?

We are directly exposed to a variety of diverse synthetic chemicals on a daily basis, for example when using cleaning products, cosmetics, drugs, plastics, and food additives. Many of these chemicals, e.g. environmental phenols, phthalates, and herbicides, can be detected in human blood or urine samples. Accordingly, due to the constant exposure to chemicals, it is essential to evaluate potential hazards and health risks. Within the EU’s REACH program and the US National Toxicity Program, chemicals are studied for their potential endocrine disrupting effects. At the same time, alternatives to in vivo testing in the form of in silico / in vitro testing are evaluated.

This picture shows an environmental chemical called Tetrabrombisphenol (which is a fireproofing agent and commonly occurs in plastic). Tetrabrombisphenol is an agonist of the peroxisome proliferator-activated receptor gamma. This receptor regulates blood sugar levels and is jointly responsible for fat storage. The substance could therefore be responsible for weight gain.

In silico predictions are highly useful to prioritize chemicals for in vitro / in vivo testing. Pharmacophore models are excellent in silico screening tools to select potentially active compounds from large chemical databases. However, so far they have hardly been used to suggest chemicals for toxicity evaluations. In the proposed project, a pharmacophore-based in silico screening platform is being developed to prioritize chemicals for mechanism-based toxicity evaluations. This platform focuses on 14 steroidsynthesizing and -metabolizing enzymes, which have not been considered in systematic toxicity studies so far. For each target, models are experimentally validated to optimize their predictive power.
Environmental chemical databases are screened for potentially active compounds. Among the virtual hits, chemicals with direct consumer exposure or high annual production volume are acquired and tested in vitro. Identified active chemical classes are further investigated by testing structurally related compounds in the in vitro assays. Based on all experimental results, the pharmacophore models are optimized to correctly separate active from inactive chemicals on the respective targets. For the studied chemical classes, structure-activity-relationship models are be built to further optimize the predictions within the respective compound class.

This picture shows the structure and the binding pocket of the protein-tyrosin-phosphatase 1B. Through the thorough analysis of the binding pocket's structure it is possible to purposefully design agents for this point of application. These could be utilized as antidiabetics one day.

The developed model collection and exemplified case studies will lay ground for future, systematic safety evaluations of chemicals. In the future, such in silico platforms combined with in vitro testing are expected to form one basis for toxicity predictions.

This picture shows the simulation of the ZIP9 receptors in the cell membrane. It is a zinc-transporter which is regulated by testosterone. However, the precise relationships are still vague. Furthermore the exact function of the receptors still needs to be researched. Through molecular simulations new ideas and insights of the ion channel can be generated. As a result correlating lab experiments can be planned which will lead to further results. 

Equipment

Hardware used:

  • Tecan Spark plate reader with fusion optic (monochromator as well as filter technique) and imaging module for absorbance, fluorescence and luminescence measurements as well as for cell counting and RNA/DNA quantification (nanoquant plate)

 extinction filter

emission filter

320 (25 nm)465 (35 nm)
340 (20 nm)535 (10 nm)
485 (20 nm)590 (10 nm)
530 (25 nm)620 (10 nm)
560 (10 nm)665 (8.5 nm)
590 (20 nm)680 (30 nm)
  • Tecan F50 plate reader for absorbance measurements (filter: 405, 450, 492, 595 and 620 nm
  • Olympus CKX53F microscope equipped with a SC50 5-megapixel colour camera
  • Bio-Rad Chemidoc imaging system for stain-free gels and blots, fluorescence multiplexing, chemiluminescence as well as ethidium bromide and SYPRO ruby detection
  • Bio-Rad CFX96 touch real-time PCR system

Software used:

  • i:lib diverse and Ligand Scout (available from Inte:Ligand)
  • Discovery Studio (available from Accelrys)
  • GOLD (available from the Cambridge Crystallographic Data Centre)

Research Cooperations

Prof. Ing. Mag. Dr. Thomas Hofer, Universität Innsbruck, Austria

Prof. Dr. Alex Odermatt, Universität Basel, Switzerland

Prof. Dr. Oliver Werz, Friedrich-Schiller-Universität Jena, Germany

Prof. Dr. Rolf Hartmann, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany

Prof. DDR. Jerzy Adamski, Hemholtz Zentrum München, Germany

Prof. Dr. Miriam de Barcellos Falkenberg, Universidade Federal de Santa Catarina, Florianópolis, Brazil

Ing. Premysl Landa, PhD, Institute of Experimental Botany AS CR, Praha, Czech Republic

Prof. Dr. Judith Rollinger, Universität Wien, Austria

Prof. Dr. Rohan Davis, Griffith University, Brisbane, Australia

Prof. Rosanna Filosa, Seconda Univerità degli Studi di Napoli, Italy

Prof. Claudia Sissi, Università degli Studi di Padova, Italy

Publications

You can find the publications of the Institute of Pharmacy at the Forschunsdatenbank PMU-SQQUID.

The existing publications of the head of the Institute of Pharmacy, professor Johanna Pachmayr, are available here.

The existing publications of the head of the Department of Pharmaceutical and Medical Chemistry, professor Daniela Schuster, are available here.

You can find the existing publications of our employees under their respective names:

News

 

Institute of Pharmacy wins Best Oral Presentation at ÖPhG 2019

Our colleague Dr. Maximilian Ardelt won Best Oral Presentation at the 26th Scientific Congress of the Austrian Pharmaceutical Society (ÖPhG). We congratulate Dr. Ardelt on his win!

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Is vitamin E anti-inflammatory?

A new article was just released in Nature Communcations magazine. In it Prof. Daniela Schuster, together with a number of her colleagues, looks at vitamin E metabolites and their anti-inflammatory effects. How high the intake should be and whether it is enough to "eat well" in order to reap those benefits is thoroughly discussed in this article.

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Cannabis: medicinal plant of the year!
The HERBAL MEDICINAL PRODUCTS PLATFORM AUSTRIA (HMPPA) voted cannabis Austria's medicinal plant of the year 2018. In honor of this year's selection there will be a scientific symposium called Cannabis - Phytochemical, Pharmacological and Clinical Evidence. The event will take place on November 15th 2018, 09:00 – 17:30 h at the University of Vienna, Universitätsring 1, Kleiner Festsaal, 1010 Vienna, Austria. Click here for further details.

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New article in Hepatology Journal
A new article called Inhibition of Cyclin-dependent Kinase 5 – a Novel Strategy to Improve Sorafenib Response in HCC Therapy was published in the Hepatology Journal. It was written by Maximilian Ardelt, professor Johanna Pachmayr, who is the head of the Institute of Pharmacy, and our PhD student Martina Meßner. If you would like to learn more about the article click on this link.

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Pharmacy get together 201

At the end of July our Institute of Pharmacy and the Department of Pharmacy from the Ludwig-Maximilians-University Munich met for a get together in Salzburg. During the event we set out to climb one of Salzburg's local mountains, the Kapuzinerberg. It was the perfect time to nurture established relationships and to talk about upcoming projects. The day ended with food and drinks in a traditional "Gastgarten" (pub garden).

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New research paper published in European Journal of Medicinal Chemistry
The most recent issue of the European Journal of Medicinal Chemistry features a research paper by Prof. Daniela Schuster. The title is Discovery of a benzenesulfonamide-based dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase that favorably modulates lipid mediator biosynthesis in inflammation. The first 50 people who click on this link will be able to download the paper for free.

 

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New release
Applied Chemoinformatics: Achievements and Future Opportunities (Apr. 2018) edited by Engel, Thomas and Gasteiger, Johann with a chapter about Chemoinformatics in Natural Products Research, by Teresa Kaserer, Univ. Prof. Dr. Daniela Schuster (director of Pharmaceutical and Medicinal Chemistry) and Judith M. Rollinger.

 

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New release
Computational Toxicology: Risk Assessment for Chemicals (Feb. 2018) edited by Sean Ekins with a chapter about PharmacophoreModels for Toxicology Prediction, by Univ. Prof. Dr. Daniela Schuster (director of Pharmaceutical and Medicinal Chemistry).