MDC scientist receives 1 million euros for diabetic research

Helmholtz Association of German Research CentresSep 21 2009

Can liver cells replace defective insulin-producing cells?

A European Research Council (ERC) Starting Grant worth more than a million euros over the next five years has been awarded to Dr. Francesca M. Spagnoli of the Max Delbr-ck Center for Molecular Medicine (MDC) Berlin-Buch, Germany. For nearly a year Dr. Spagnoli has been leading a Helmholtz junior research group at MDC, an institution of the Helmholtz Association, and at Charit- - Universit-tsmedizin Berlin. Together with the biophysicist Dr. Leif Schr-der from the Leibniz Institut f-r Molekulare Pharmakologie (FMP), also on the Berlin-Buch Campus, Dr. Spagnoli belongs to the 240 top scientists the ERC has chosen from more than 2, 500 applicants.

The research project of Dr. Spagnoli will investigate the possibility of reprogramming hepatic cells to pancreas cells so that they can ultimately replace the destroyed pancreatic beta cells and produce the vital hormone insulin in diabetic patients.

Dr. Spagnoli is originally from Italy and has two doctorate degrees, one in medicine and the other in genetics and cell biology. Her major field of interest is stem cell research, and she is currently investigating the embryonic development of beta cells in the Langerhans' islets of the pancreas and also the embryonic development of hepatic cells.

Beta cells produce the hormone insulin which regulates the blood glucose levels, the body's main source of energy. In patients with type 1 diabetes the beta cells have been destroyed due to a misguided response of the immune system, and blood glucose levels are elevated.

These patients must self-inject insulin throughout their whole life. Even in patients with type 2 diabetes, who initially can be treated with a special diet and pills, the beta cells can decline and fail over time, so that these patients, too, must self-inject insulin.

Insulin replacement therapy, however, has adverse side effects. This is why physicians have been trying for a long time to transplant intact beta cells or whole pancreas organs, but with little success. According to Dr. Spagnoli, there are several reasons for this.

One is a shortage of donors; another is that the transplanted organ or cells frequently do not function well. After five years the patients often need a new transplant or have to self-inject insulin again.

The reason why Dr. Spagnoli intends to compare beta cells and hepatic cells is that the pancreas and the liver have a lot in common. "Both organs derive from the same region in the embryo, and both play an important role in metabolism and in blood glucose regulation," she explained. "Moreover, they share a number of genes."

Dr. Spagnoli wants to investigate whether beta cells and hepatic cells arise from a common bipotent progenitor cell. She hopes to identify the molecular signals that determine why one progenitor cell develops into a hepatic cell and another into a beta cell.

"We want to elucidate the factors that determine this difference," she said. Her approach is to start from this interface to see whether it is possible to reprogram adult hepatic cells to pancreatic beta cells so that they are able to produce insulin. By bypassing the use of embryonic stem cells for her investigation, she hopes to shorten and simplify the reprogramming process.

Dr. Spagnoli studied medicine and received her MD at La Sapienza University in Rome, Italy, and completed an additional doctorate in genetics and cell biology at the Pasteur Institute in Paris, France.

Prior to coming to Berlin in 2008 to conduct her research at MDC, she worked in the laboratory of Professor Ali Hemmati-Brivanlou at Rockefeller University in New York, USA, one of the leading laboratories in the field of stem cell research and developmental biology.

The European Research Council, established in 2007 by the European Commission, is funded through the 7th Research Framework Programme of the European Union.