Richard Mortensen
Photo: D.C. Goings

Richard Mortensen has nothing against mice — the traditional workhorse of biomedical research. It’s just that stem cells provide a faster, cheaper and more efficient way to identify the effect of one particular gene on a living organism.

Mortensen specializes in developing knock-out lines of embryonic stem cells. By carefully removing or “knocking-out” a gene from mouse DNA and then culturing the genetically altered stem cells, he sees the effect in days, instead of the months it takes to breed mice and see results in their offspring.

The newest stem cell scientist in the Medical School, Mortensen left Harvard Medical School in June 2000 to join the faculty at U-M. He brought with him embryonic stem cell lines with inactivated genes, which can be differentiated into cardiomyocytes in culture. Cardiomyo-cytes are partially differentiated cells midway on the developmental pathway between stem cells and specialized cardiac cells in heart tissue. Mortensen uses these cell lines in research to define gene targets for treatment of cardiovascular disease.

“No one has found a cardiac stem cell and we know very little about the mechanisms that drive development of cardiac cells from cardiocytes,” says Mortensen, as he prepares to view the stem cells — beating spontaneously in their culture dish — under a microscope. “We can maintain these cell colonies for several weeks, but hope to find ways to extend them long enough to see them differentiate into adult-like atrial and ventricular cells.”

With U-M colleagues Sue O’Shea and Edward Stuenkel, Ph.D., associate professor of physiology, Mortensen hopes to begin a new research study. Their goal will be to identify all the different factors regulating insulin secretion by specialized cells in the pancreas called beta cells. Mortensen plans to use human embryonic stem cells to develop new cell lines of insulin-secreting beta cells and then knock out specific genes to determine their impact on insulin production. Knowing all the signaling molecules and proteins that control how beta cells react to glucose and understanding how they work could one day lead to a new cell therapy for diabetes.

Matthew Merrins
Photo: Martin Vloet

Matthew Merrins, a first-year U-M graduate student in physiology, will be helping Mortensen create the new line of beta islet cells — the fist such cell line to be developed at the U-M Medical School. “I’ll be the one developing the selection and purification scheme for the embryonic stem cells,” Merrins says. “Just as the stem cells begin to differentiate, we want to select out only those cells differentiating along a specific neuronal lineage pathway. Then we will use hormones and other tech-niques to get the cells to switch from neural lineage to beta islet development.”

Also:

Unlocking the Secrets of Stem Cells

A Stem Cell Glossary