Main Contribution to Research

(status March 2018, individual citation numbers are from Google Scholar because this database is freely accessible.

 

Dr. Sieghart so far has published 281 articles in peer reviewed journals, plus 31 proceedings, 7 invited book articles, >540 abstracts, and 3 patents, and has been cited (status of March 2018).

As stated in a citation analysis published in 2002 and 2006 by a German laboratory journal, the basic neuroscience and the clinical neuroscience papers published by Dr. Sieghart between 1997 and 1999 and between 2000 and 2002, respectively, belonged to the most highly cited publications of Germany, Switzerland and Austria in these fields.

 

Selected publications in the last 10 years before retirement (2005-2014)

 

Detailed overview on the research topics of Dr. Sieghart and his most relevant publications

During work on his PhD thesis he concentrated on transport processes in yeast mitochondria at the Department of Biochemistry, University of Vienna, (under the supervision of Prof. Dr. Hans Tuppy).

During the first years of his postdoctoral studies at the University Clinic for Psychiatry, his basic research in Neuroscience concentrated on the investigation of taurine as a possible neurotransmitter (under the supervision of Prof. Manfred Karobath).

In that time, he for the first time demonstrated

During his postdoctoral studies in the lab of Prof. Paul Greengard, Yale University, Dept of Pharmacology, Connecticut, USA, (Nobel price winner in 2000, in Physiology and Medicine), he concentrated on the investigation of protein phosphorylation processes during secretion of mast cells and in the function of the brain.

He for the first time demonstrated

In the subsequent 36 years he concentrated on the investigation of GABAA receptors:

He for the first time demonstrated

 

He first identified

 

He developed a concept for a

 

His homology modelling studies

Antibodies:

Immunoaffinity purification and determination of GABAA receptor subunit composition and stoichiometry, as well as of changes in receptor composition under various pathological conditions, required the generation of large amounts of absolutely subunit-specific antibodies.

Before 1989, a total of 8 attempts for generating monoclonal antibodies from hybridomas generated from mice immunized with GABAA receptors purified from 8-10 day old rats failed. Although monoclonal antibodies were obtained that recognized purified GABAA receptors, none was subunit- or receptor subtype-selective.

As soon as the first GABAA receptor subunits had been cloned by the group of P. Seeburg, amino acid sequences of the GABAA receptor subunits allowed a more specific strategy. Subunit-specific peptides or subunit-specific fusion proteins directed against different epitopes of the individual subunits were generated for immunization of animals. From 1989-2012 antibodies were generated from

  • a total of 347 rabbits
  • 42 guinea pigs
  • 49 mice
  • 24 rats

Generation, purification and characterization of antibodies was thus a major effort of the lab of W. Sieghart. Up to 4 students or technicians were working more or less continuously for 20 years to generate and characterize the largest collection of GABAA receptor subunit-specific antibodies currently available, that were then used for the immunoaffinity purification and for immunoprecipitation of GABAA receptors containing specific subunits.

The large number of distinct GABAA receptor subtype-selective antibodies generated also could be used for immunohistochemistry, but selection of antibodies suitable for immunohistochemistry was more difficult than the identification of receptor subtype-selective antibodies for immunoprecipitation and Western blots. Although the very first antibodies generated could successfully be used for immunohistochemistry and resulted in the

subsequent antibodies were not as suitable for immunohistochemistry. And in the first external collaboration with Peter Somogyi, many antibodies had to be provided to him to be tested in immunohistochemistry and electron microscopy studies. Most of the antibodies provided were not suitable for immunohistochemistry, but some were, and resulted in a series of important collaborative publications on the cellular and subcellular localization of various GABAA receptor subtypes.

In another long-term collaboration with Günther Sperk actually hundreds of affinity-purified antibodies generated and isolated by W. Sieghart and his group were tested by Günther Sperk for immunohistochemistry. Günther Sperk selected the best out of these hundreds of antibodies and succeeded to publish

 

In further collaborative studies, the GABAA receptor subunit-specific antibodies of W. Sieghart

 

His work on GABAA receptor heterogeneity, subunit composition, structure, and pharmacology of GABAA receptor subtypes, led to his membership in the International Union of Basic and Clinical Pharmacology (IUPHAR) GABAA receptor classification committee and resulted in highly cited comprehensive reviews on this topic:

Current research topics:

  • Development of GABAA receptor subtype-selective compounds and investigation of their importance for the treatment of various diseases in preclinical studies
  • Immunohistochemical investigations of the regional, cellular, and subcellular distribution of GABAA receptor subunits in the rat, mouse, and human brain

Clinical studies:

Having served for 21 years (1980-2001) as a chief of the Section of Biochemical Psychiatry and as a Chief of a Clinical Chemistry Laboratory at the University Clinic for Psychiatry, he also established and performed hormone determinations as well as molecular genetic investigations for clinical research. His work and his collaboration with clinicians contributed to a variety of well cited clinical publications:

 

In this overview, a total of 122 of the 279 peer reviewed publications of Dr. Sieghart are listed. The remaining publications can be found in Google Scholar under „Werner Sieghart“ together with their numbers of citation.