phone: +358 9 191 26595
fax: + 358 9 191 25155
e-mail:
firstname.surname@helsinki.fi

Research:

The main emphasis is on pathological processes taking over in the wall of an injured artery. Analysis of vascular injury encompasses all aspects of cell biology - proliferation, adhesion, cell death, inflammatory response, (de)differentation, connective tissue production. As it is impossible to get human samples to analyze the time course of vascular injury on molecular level, most of the information is collected indirectly using model experiments.

Currently we use two types of injury models (mechanical and immunological) in three different experimental animal species (rat, mouse and baboon). Mechanical injury (angioplasty, balloon dilatation) injury is introduced to carotid artery and aorta. Heart and kidney transplantations are performed in mice and rats. Aorta transplantations are performed in mice, rats and baboons.

Analysis of experimental data combines histological (computerized morphometry), immunohistochemical and molecular (microarray, real time quantitative PCR) evidence to build a tentative working model. Models are verified/falsified using candidate drug molecules either to revert or, at least, to inhibit the pathological processes destroying tissue integrity after transplantation or angioplasty.

After sufficient information of the mechanisms and the genomics of the injury in primates (baboons) and additional studies in rodents, several rate-limiting genes/proteins have been identified (proposed molecule; collaborating company):

• IGF1-R (antagonist peptides)
• PDGF-R (RTK-inhibitor peptidomimetics)
• Estrogen receptor beta (selective agonists; KaroBio and Schering)
• Somatostatin receptor subtype 1,4 (selective agonists; Juvantia Pharma and
• Alcon)
• mTOR (inhbititors used in clinical trials; Wyeth)

The Program has been a partner with the following Companies to design new and novel molecules towards unmet medical needs:

• KaroBio: vascular disorders
• Juvantia Pharma: vascular, ophtalmological and neurological indications
• Wyeth: design and conduction of clinical trials for the prevention of chronic rejection

Page updated July 31, 2006

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