First human stem cell grants
City of Hope investigator receives one of California’s first human stem cell grants
On a minute scale, stem cells do the same for their chromosomal DNA, fixing splits and breaches in it. But how well do they do it?
A noted City of Hope investigator wants to find out.
Timothy O’Connor, Ph.D., professor in the Division of Biology, was recently awarded one of the first grants to fund human embryonic stem cell research resulting from passage of California’s Proposition 71, also known as the California Stem Cell Research and Cures Initiative. The grant funds his work in DNA repair.
O’Connor shared the honor with Prop.71 investigators statewide, according to the California Institute for Regenerative Medicine (CIRM). These SEED (for Scientific Excellence through Exploration and Development) grants are awarded to experts working outside the embryonic stem cell field in the hope that they bring novel insight to stem cell biology.
For 20 years, first at the Institut Gustave Roussy in Villejuif, France, and in the last 10 at City of Hope, O’Connor has identified proteins that repair nicks and breaks in chromosomal DNA. “We are interested in how cells protect themselves from DNA damage, and how those strategies can be exploited for possible therapy,” he said.
Breaks in double-helical DNA strands occur following exposure to mutagens or radiation and much less frequently during normal cell division. Healthy cells express legions of proteins whose job is to repair battered DNA. Without them, cells can die or become cancer cells.
Although the amount is not yet finalized, the CIRM governing board will award O’Connor about $350,000 over two years to determine how efficiently DNA repair proteins operate in human embryonic stem, or ES, cells. Funds will support specialists who know how to make finicky stem cells thrive in a Petri dish. “ES cells take a lot of care and feeding,” explained O’Connor.
Steven Bates, a senior research associate at City of Hope since 1992, will handle the cells’ care. Bates devised a unique method to prepare “feeder” or support cells used to maintain ES cells in culture.
Some studies suggest that over long periods, ES cells accumulate mutations, or errors in their DNA sequence, more readily than other cells. “Our goal is to try to understand if repair processes differ at these very early stages of development from repair processes operating in cells that have developed into more mature cell types,” O’Connor said.
One technique O’Connor will use to accomplish that is to mutate a gene encoding a protein called luciferase, which emits light. The scientist then forces that nonfunctional luciferase gene into an ES cell and waits to see if it will glow. “After different time points, say eight to 48 hours, we can start to see a signal — that’s an indication that repair has occurred,” O’Connor said. Researchers then will compare the repair rate to that in non-ES cells.
O’Connor says that scientists must determine how vulnerable human ES cells are to DNA damage before they are infused into people as replacement therapies. “It is not yet clear what will happen when you put a living stem cell into a person, so it is very important to understand what that cell is doing. It’s not like a drug that you can stop giving to someone,” O’Connor said.
The hope is that tissues derived from stem cells will last a lifetime. O’Connor’s work is aimed at making sure that ES cell replacement therapy is a good thing.
Markie RamirezTimothy O’Connor