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Interview with Michaela Golić

In April, Clinician Scientist Michaela Golić and Ralf Dechend rom the TRG Fetal programming of cardiometabolic disease received the Paper of the Month award

What do you research? What is at the core of your research? What is the motivation behind your research?

We conduct research in the field of fetal programming, which focuses on the long-term health impacts of certain environmental factors in the early period of development, particularly during pregnancy. This concept was co-founded several decades ago by researchers at Charité and has since developed into a popular area of research.The mother’s body and its metabolic state create the environment in which the fetus grows inside the uterus. This means that maternal diseases such as diabetes mellitus, characterized by elevated blood sugar levels in the pregnant woman, are also relevant for the fetus. Our research focuses in particular on the influence maternal diabetes has on offspring during pregnancy.Fetal programming seems to manifest itself in the form of epigenetic modifications that affect gene activity without altering the genes themselves. This interaction between environmental factors and genes and the ability of these genes to be passed on is extremely exciting and is really what motivates our research, just as it has many generations of researchers before us – presumably because evolutionary findings such as these are also an important part of human identity.

What is the central message of your publication and how does your study differ from the work of other scientists in this field?

We were able to use an animal model to show that maternal diabetes during pregnancy reduces the gene expression of an important regulator of cholesterol metabolism, and that this change is accompanied by an epigenetic modification. More specifically, we were able to show that, compared to fetuses of healthy mothers, the sterol regulatory element binding transcription factor 2 (Srebf2) displays decreased transcription in the fetuses of diabetic mothers, and that this is associated with CpG hypermethylation of the Srebf2 promoter. At the same time, the fetuses of diabetic mothers have a different body weight. Our results fit in very well with the existing concept of fetal programming, which until now has been largely described at the epidemiological level. Our results now present a concrete candidate on the molecular level – one that reacts to the intrauterine environment through epigenetic changes and that could therefore mediate diseases in later life.

Who did you collaborate with on this publication? Who were the key participants?

A large part of the publication was produced through work done at the Experimental and Clinical Research Center (ECRC), a joint institution of Charité – Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), though many of the researchers involved are affiliated with Berlin Institute of Health (BIH) and/or the German Center for Cardiovascular Research (DZHK). In addition to cooperation partners at these institutions, we also worked with other partners in Germany and abroad. Prof. Sicco Scherjon, Dr. Torsten Plösch, and Violeta Stojanovska (University of Groningen in the Netherlands) helped us with the epigenetic analyses, and we cooperated with Prof. Ursula Felderhoff-Müser and Prof. Ivo Bendix (Essen University Hospital) in the investigation of fetal brains.

What are the next steps for the project and what are the possible implications of your findings for patients?

It is very important that we now investigate whether the changes we witnessed in the fetuses of diabetic mothers continue to exist into adulthood. These investigations are currently underway. Following this, we would need to examine whether the same results are found in humans.