Targeting Cancer
In a paper published in the journal Science, OMRF’s Drs. Dean Dawson and Regis Meyer have revealed how two genes—known as IPL1 and MPS1—are integral to the correct division of cells and life itself. If these genes can be controlled, it could help physicians target and destroy pre-cancerous cells or prevent birth defects.
In the laboratory, the researchers used high-powered microscopes to observe the process of cell division in yeast cells. But as they watched,
Meyer and Dawson observed something unexpected: The cells made
a lot of mistakes.
“About 80 percent of the time, the cell would begin pulling both copies off to the same side instead of pulling one towards each new daughter cell,” Dawson says. “If the cell divided like that, you’d have all sorts of problems. Inappropriate chromosome numbers is a leading cause of birth defects and is a common feature of tumor cells.”
With further study, the scientists discovered that the IPL1 and MPS1 genes act as quality controllers. When a chromosome gets pulled to the wrong side, the two genes correct the
problem. “These genes are master regulators. If they’re
removed, the entire process goes haywire,” Dawson says.
Several groups are now investigating ways to target IPL1 and MPS1 as potential anti-cancer treatments. According to Dawson, the OMRF research will boost those efforts. “When you understand exactly how the process works,
you know how to better craft a treatment,” he says.
The Price of Fatty Foods
When OMRF scientists studied the heart cells of mice that ate a high-fat diet, they discovered something counterintuitive. “We found a reaction similar to what happens with starvation,” says Dr. Mike Kinter, who worked with Drs. Luke Szweda and Paul Rindler on the study. “In a sense, it tricks the cells into burning fat instead of glucose.” While that may sound like a good thing, it’s not. Over time, the resulting build-up of excess sugar in the bloodstream can lead to type 2 diabetes, nerve damage, kidney and eye problems, heart disease and stroke.
The research, which appears in The Journal of Biological Chemistry, gives scientists insight into why cells begin burning fat instead of glucose. “Our bodies just haven’t evolved to deal with the modern problems of too much food and not enough exercise,” says Szweda. Follow-up studies will look at the related issue of insulin dependency and could give researchers clues on how to reverse type 2 diabetes.
New Life for Old Cells
When people age, so do their cells. This process takes a particular toll on stem cells, which play a key role in fighting infections. “As stem cells grow older, their ability to make lymphocytes is diminished,” says OMRF’s Dr. Paul Kincade. “That compromises the body’s ability to fight infections and could explain why older patients have so much more trouble fighting even common illnesses.”
In collaboration with researchers at the Osaka University Graduate School of Medicine in Japan, Kincade helped stimulate the stem cells of laboratory mice to make more of a protein known as Satb1. The result: The animals’ stem cells regained much of their ability to create lymphocytes.
Published in the journal Immunity, the new findings might help replenish stem cells as people grow older and aid in reducing age-related illness from infections. “At least in mice,” says Kincade, “this looks like a fountain of youth for the immune system.”
Platelet Power
One way the immune system keeps a body healthy is through immune surveillance. Lymphocytes, a type of white blood cell, constantly exit the bloodstream and “check in” at the lymph nodes to learn about possible pathogens or abnormal cell growth. The function prepares the immune system to fight infections and dispose of pre-cancerous cells.
For years, scientists have wondered how lymphocytes exit the bloodstream at a large volume without causing bleeding. A team of OMRF researchers led by Dr. Lijun Xia found that platelets, which normally stop blood loss by clumping and forming plugs in blood vessel holes after injuries, activate a screening process. This process allows lymphocytes to exit into lymph nodes without letting red blood cells leave the blood vessel.
Drs. Xia, Jianxin Fu and Brett Herzog detailed the research in the journal Nature. The findings could alter the ways doctors use platelets to treat traumatic injuries and serious infections.
“This is a prime example of the important research that the Institutional Development Award program makes possible,” says Dr. María Teresa Canto of the NIH, which provided funding for the research. “Dr. Xia’s study sheds light on a process that is key to vascular health as well as to the development of inflammation and associated diseases.”
