Biomedical subjects

Stefan W Henning

Publications and source records attributed to Stefan W Henning.

4 recordsLinked to original sources

PubMed2004

Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness.

Tumour cell invasiveness is crucial for cancer metastasis and is not yet understood. Here we describe two functional screens for proteins required for the invasion of fibrosarcoma cells that identified the molecular chaperone heat shock protein 90 (hsp90). The hsp90 alpha isoform, but not hsp90 beta, is expressed extracellularly where it interacts with the matrix metalloproteinase 2 (MMP2). Inhibition of extracellular hsp90 alpha decreases both MMP2 activity and invasiveness. This role for extracellular hsp90 alpha in MMP2 activation indicates that cell-impermeant anti-hsp90 drugs might decrease invasiveness without the concerns inherent in inhibiting intracellular hsp90.

Basement Membrane↗

PubMed2003

Beyond the genome--SMi Conference 27-28 January 2003, London, UK.

Over a decade of astonishing developments, genomics and proteomics have promised a fundamentally new approach to drug discovery. Although there has been an undeniable increase in the range of potential targets available, this has not led to an increased output of the drug discovery pipeline into the clinic. With tighter markets and increasing competition, the major pharmaceutical companies are under intense pressure to achieve rapid, concrete delivery of those early promises, but there remain acute problems in the genes-to-drugs pipeline. This meeting showcased a range of novel approaches from proteomics and bioinformatics to address these problems. A common theme in the range of proteomics offerings was the prioritization of potential novel targets on the basis of their accessibility to drugs and their functional link to disease phenotypes. Informatics and in silico offerings also concentrated on fast, accurate, drug-focused workflows built on large integrative databases and novel data-mined algorithms.

Animals↗

PubMed2002

Emerging high-throughput drug target validation technologies.

Identifying the right target for drug development is a critical bottleneck in the pharmaceutical and biotech industries. The genomics revolution has shifted the problem from a scarcity of targets to a surplus of putative drug targets. As the validity of a target cannot be simply inferred from correlative data, the key is confirmation of the causative role of a gene product in a particular disease. It should therefore be recognized that an effective therapeutic strategy requires an appropriate target validation technology to verify the right target.

Biotechnology↗

PubMedDate not supplied

Toward understanding the mechanism of chromophore-assisted laser inactivation--evidence for the primary photochemical steps.

Chromophore-assisted laser inactivation (CALI) is a light-mediated technique used to selectively inactivate proteins of interest to elucidate their biological function. CALI has potential applications to a wide array of biological questions, and its efficiency allows for high-throughput application. A solid understanding of its underlying photochemical mechanism is still missing. In this study, we address the CALI mechanism using a simplified model system consisting of the enzyme beta-galactosidase as target protein and the common dye fluorescein. We demonstrate that protein photoinactivation is independent from dye photobleaching and provide evidence that the first singlet state of the chromophore is the relevant transient state for the initiation of CALI. Furthermore, the inactivation process was shown to be dependent on oxygen and likely to be based on photooxidation of the target protein via singlet oxygen. The simple model system used in this study may be further applied to identify and optimize other CALI chromophores.

Absorption↗