Timo Otonkoski

Tackling diabetes by reprogramming cells

Timo Otonkoski, HUS Children and Adolescents

Professor Timo Otonkoski’s research group studies the mechanisms of pluripotency and the biology of pancreatic beta cells. The objective is to develop new treatment methods for the insulin deficiency which lies in the background of diabetes.

– We are searching for answers to questions such as how the gene defects in pancreatic beta cells lead to the development of diabetes or congenital hyperinsulinism, where the pancreas secretes too much insulin. We want to find out whether a stem-cell-based beta cell model can be used to discover new remedies for these diseases, Timo Otonkoski says.

Among other things, the research group studies whether human cells can be reprogrammed to early stem cell stages by modifying the operation of genes found in the cells themselves so that the stem cells produced are ‘healthier’ than the cells produced by means of older methods.

Researchers are also interested in the operation of the genes which are the first to be activated when a human embryo develops. In addition, the objective is to examine the regulation of the development of the metabolism of pancreatic beta cells, where cells begin to secrete insulin based on the glucose level.

Putting stem cell technology to good use

Otonkoski says that the most recent potential of stem cell technology and genome modification is being used. These methods can be used to produce so-called iPS cells in laboratory conditions.

– We have shown that regulating the manifestation of genes by means of CRISPR activators is an efficient way to control the reprogramming and differentiation of cells. For the first time in the world, we have used this method to produce iPS stem cells by exclusively activating the genes found in the cells themselves, Otonkoski explains.

From stem cells to beta cells

Next, an attempt is made to optimise the method in order to be able to reprogram stem cells directly for instance into nerve cells, heart cells or beta cells.

The research group has developed an efficient method to differentiate the iPS cells into pancreatic beta-like cells. It has been possible to use it in combination with mutation correction for examining the mechanisms of neonatal diabetes, a rare type of diabetes diagnosed at under six months of age. iPS stem cells produced from the patient’s skin cells have been used to examine the mechanisms of several new genes causing neonatal diabetes.

The research group includes approximately 20 people, most of whom are biologists. The group includes two docents, five postdoc students, five PhD students, several undergraduate students and four technicians. The same group is also in charge of the operation of the stem cell Core Facility of the Medical Faculty.

The research group began to form when Otonkoski returned from his own postdoc period in the United States in 1994. The group initially operated at the Haartman Institute transplantation laboratory. Since 2001, it has been part of the Biomedicum research programmes. Starting in 2019, the group will belong to the new STEMM research programme involving several researchers from the Children’s Hospital.

Contact details

Timo Otonkoski
Children’s Hospital, University of Helsinki