Research Highlights - Promise Autumn 2014

Pui elected to Academia Sinica

St. Jude Oncology Chair Ching-Hon Pui, MD, has been elected as an Academician of Academia Sinica. The honor is given in recognition of Pui’s research, which has successfully eliminated the need for radiation in the treatment of leukemia and helped push childhood leukemia survival rates to unprecedented heights. The election also honors Pui for his work with doctors worldwide to further the study and treatment of childhood cancer.

Headquartered in Taipei, Academia Sinica supports research activities in disciplines such as mathematics and physical sciences, life sciences, humanities and social sciences. The Convocation of the Academia Sinica includes more than 200 distinguished scientists.

“Dr. Pui’s work has changed the way the world thinks about and treats childhood leukemia,” said James R. Downing, MD, St. Jude president and chief executive officer. “This honor recognizes his leadership, pioneering research and contributions, made not only to children at St. Jude, but to pediatric cancer patients across the globe.

St. Jude celebrates siblings

Luca de Jong and other St. Jude siblings walk the red carpet as part of the annual Sibling Star Day event held this summer. The event recognizes brothers and sisters of St. Jude patients for their all-star efforts. The St. Jude Child Life Program hosted the sports-themed day of activities for siblings, ages 4 to 19.

Siblings decorated and personalized sports pennants, waving them proudly during a red-carpet walk from the front entrance of the hospital to the Danny Thomas/ALSAC Pavilion. Employees and volunteers lined the route, cheering and applauding the honorees. The siblings also received medals to honor their contributions as part of the patient care team.

St. Jude receives top honor for supporting military personnel

St. Jude has received the highest honor given by the U.S. government to recognize employers who provide exceptional support of employees serving in the National Guard and Reserve. Of more than 2,800 U.S. corporations nominated, St. Jude was chosen as one of 15 to receive the Secretary of Defense Employer Support Freedom Award from the Employer Support of the Guard and Reserve of the Department of Defense.

“We deeply appreciate our employees who serve in the military for their contributions to the St. Jude mission and to our country,” said James R. Downing, MD, St. Jude president and chief executive officer. “We are honored to receive this recognition and gratified to know that our employees appreciate our support of them and their families during times of deployment.”

Army National Guardsman Curtis Johnson, Facilities Operations and Management, and veteran Racquel Collins, PhD, Pathology, are two of approximately 100 hospital employees who are veterans or are on active duty.

Lifestyle choices especially important for childhood cancer survivors

Adult survivors of childhood cancer who don’t get enough exercise and eat an unhealthy diet more than double their chances of developing metabolic syndrome. This disorder includes symptoms like high blood pressure and a large waistline. Those factors increase the risk of heart disease, diabetes and other serious health problems.

St. Jude researchers found the link by studying 1,598 childhood cancer survivors. They ranged in age from 19 to 60 years old. All were enrolled in the unique St. Jude LIFE study, in which adults who were treated at St. Jude as children return to the hospital for tests. The tests help scientists learn more about the health challenges facing childhood cancer survivors.

Of the survivors in this study, almost a third had metabolic syndrome, and nearly three-quarters did not follow a heart-healthy lifestyle. Lifestyle contributed to survivors’ odds of developing metabolic syndrome more strongly than did risk factors related to their cancer treatment.

“The findings suggest that if childhood cancer survivors maintain a healthy lifestyle by staying active and eating a diet low in fat, sugar and salt, and rich in fruit and vegetables, they should be able to influence whether or not they develop metabolic syndrome,” said Kirsten Ness, PhD, of St. Jude Epidemiology and Cancer Control.

The study appeared recently in the journal Cancer.

New leads on hushing the “voices” of schizophrenia

A missing gene and the resulting defective connection between brain structures may leave individuals vulnerable to the “voices” that are a common symptom of schizophrenia.

The St. Jude study is the first to tie a specific brain circuit to the “voices,” delusions and other psychotic symptoms of this chronic brain disorder. The circuit links parts of the brain that interpret sound.

Working in a laboratory model of schizophrenia, researchers reported that losing one copy of a gene named Dgcr8 reduced the flow of information between the brain structures. “We think this sets the stage for stress or another factor to come along and cause auditory hallucinations,” said Stanislav Zakharenko, MD, PhD, of St. Jude Developmental Neurobiology.

The research also provides a new focus for efforts to develop drugs that quiet the “voices” of schizophrenia with fewer side effects than current medications. A report on this research appeared in the journal Science.

Attaching an “on” switch for protein regulation

Humans use accessories like boots and gloves to adapt to their environment. Inside cells, proteins accessorize too, and for similar reasons.

In this case, the “accessories” are small molecules that cells rely on to adapt to changing conditions. The small molecules attach to proteins to change their fate and function.

St. Jude scientists have discovered how an important “on” switch is attached to the cellular machinery that helps accessorize proteins. The study involved a specialized accessory called NEDD8—the “on” switch for the machinery that accessorizes 10 to 20 percent of the thousands of proteins that work in cells. The researchers discovered the mechanism that ensures NEDD8 is properly positioned on that machinery.

“This discovery is a major advance in understanding the machinery cells use to regulate an astonishingly vast number of proteins they depend on—as well as the diseases that arise when the system malfunctions,” said Brenda Schulman, PhD, of St. Jude Structural Biology, and a Howard Hughes Medical Institute investigator. Problems with NEDD8 have been associated with cancer and other diseases, including the infectiousness of HIV, the virus that causes AIDS.

The research appears in the journal Cell.

Discovery may lead to new antibiotics for staph infections

St. Jude scientists have discovered an enzyme that regulates production of the toxins that contribute to potentially life-threatening Staphylococcus aureus infections.

Researchers also showed that the same enzyme allows Staphylococcus aureus to use fatty acids acquired from the infected individual to make the membrane that bacteria need to grow and flourish.

The results provide a promising focus for efforts to develop a much-needed new class of antibiotics to combat staph and other Gram-positive infections. Staphylococcus aureus is the most common cause of staph infections, including methicillin-resistant Staphylococcus aureus (MRSA), the drug-resistant infection that is a growing problem in hospitals.

“Staphylococcus aureus is a clear and present danger to patients worldwide,” said Charles Rock, PhD, of St. Jude Infectious Diseases. “We set out to answer a long-standing question about bacterial membrane biochemistry and discovered a master regulator of the virulence factors that make staph infections so destructive and dangerous. The pathway we identified offers an exciting new target for antibiotic drug development.”

The study appeared in Proceedings of the National Academy of Sciences.

Shape-shifting protein discovery may aid drug development

St. Jude structural biologists Diana Mitrea, PhD, Richard Kriwacki, PhD, and their colleagues recently discovered the mechanism underlying a shape-shifting regulatory protein that fulfills multiple roles in the life of cells and aids in tumor suppression. The results could aid cancer drug development.

The research focused on the protein nucleophosmin 1 (NPM1), which plays a critical part not only in tumor suppression but in cell division, protein production and other cell processes. Until now, however, how NPM1 fulfilled its varied responsibilities was unknown. The study was published recently in Proceedings of the National Academy of Sciences.

Abridged from Promise, Autumn 2014

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