Michael Angelo Petr
Panum Instituttet, Blegdamsvej 3, 2200 København N
Focus 1: Developing interventions for aging via DNA repair disorders.
This focus has a multi-pronged approach.
First, we are establishing the phenotypic networks that exist amongst monogenic DNA repair disorders, a fraction of which are accelerated aging disorders, using bioinformatics analyses. These networks will eventually be tested in the wet lab.
Second, is the application of an intervention to model organisms of the DNA repair disorder Cockayne syndrome (CS), as a proof-of-principle to our in silico work. CS is a devastating rare genetic disease characterized by progressive neurodegeneration and premature aging, among other clinical symptoms. It is caused by mutations in the DNA repair genes ERCC6 (CSB) or ERCC8 (CSA), and currently there is no known treatment for these patients. Our previous work shows that acetyl-CoA and citrate levels are decreased in models of this disease suggesting that these may be key metabolites in Cockayne syndrome and perhaps aging. To test this hypothesis we have knocked out CSB and INDY, the citrate transporter, in human cell lines, fruit flies and mice and subsequently investigating aging phenotypes and a ketogenic diet in these models.
Focus 2: Re-engineering DNA repair
This focus consists of the characterization and removal of age- and DNA damage related foci in senescent cells.
In conjunction to both topics, I use 3D printing, software and electrical engineering principles to aid the research with new devices."