Research Highlights - Promise Summer 2014

Schulman elected to National Academy of Sciences

A structural biologist from St. Jude is one of the newest members of the National Academy of Sciences.

Brenda Schulman, PhD, is among 84 new members and 21 foreign associates from 15 countries selected to join the academy this year. The organization is a private, nonprofit society of distinguished scholars charged with providing independent, objective advice to the nation on matters related to science and technology. Scientists are elected by their peers based on their outstanding contributions to research.

“Dr. Schulman continues to blaze new paths using structural biology to advance global scientific understanding of how key cell processes are regulated,” said Dr. William E. Evans, St. Jude director and CEO. “Her election to the National Academy of Sciences is a richly deserved honor for her life’s work as well as for St. Jude. We are pleased, but not surprised that her work has attracted this recognition.”

Schulman is a co-director of the St. Jude Cancer Genetics, Biochemistry and Cell Biology Program. She is a faculty member in the departments of Structural Biology and Tumor Cell Biology as well as a Howard Hughes Medical Institute Investigator.

Other St. Jude researchers elected to the academy include Nobel Laureate Peter Doherty, PhD, renowned virologist Robert Webster, PhD, and esteemed tumor cell biologist Charles Sherr, MD, PhD. Several St. Jude scientists have also been elected to the Institute of Medicine, a prestigious branch of the National Academy of Sciences. They include Evans, Sherr, James Downing, MD, Mary Relling, PharmD, and Arthur Nienhuis, MD.

For brain tumor patients, age matters

Scientists at St. Jude have more evidence that age matters when it comes to the devastating brain tumors called high-grade gliomas (HGGs).

Researchers knew the genetic makeup of these tumors varied significantly between adults and children. The new findings suggest the same is true for children of different ages. In this study, investigators sifted through billions of pieces of DNA. They discovered specific genetic alterations that occurred most often in the youngest patients.

The discoveries provide clues researchers can use to fashion more effective age-specific therapies. Such treatments are urgently needed. Despite aggressive treatment with surgery, radiation and chemotherapy, fewer than 20 percent of patients with these tumors are alive two years after their cancer is diagnosed.

“This study provides striking new evidence of how high-grade gliomas differ not only between adults and children, but also between older and younger children,” said Suzanne Baker, PhD, of St. Jude Developmental Neurobiology.

The findings, published in the journal Nature Genetics, are from the St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project.

Scientists discover gene mutated in most childhood bone tumors

Scientists working on the St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project recently discovered that the tumor suppressor gene TP53 is mutated in 90 percent of osteosarcoma tumors. This finding suggests that the alteration plays a key role early in development of the bone cancer.

Michael Dyer, PhD, Developmental Neurobiology (pictured above, at right), discusses the project with colleagues Armita Bahrami, MD, of St. Jude Pathology (at left), and Xiang Chen, PhD, of the hospital’s Computational Biology department.

The discovery that TP53 is altered in nearly every osteosarcoma helps to explain why, at standard doses, radiation therapy is largely ineffective against the tumor.

“This study identifies numerous mutations in TP53 missed by previous studies that did not include whole genome sequencing,” said Dyer, who is also a Howard Hughes Medical Institute Investigator. Jinghui Zhang, PhD, of St. Jude Computational Biology, joined Dyer, Bahrami and Chen in authoring a paper on this project, which was published in the journal Cell Reports.

Molecule acts as umpire to make tough life-or-death calls

Cells may be small, but they are home to plenty of mystery and drama. Take the enzyme known as RIPK1. St. Jude scientists have just determined that after birth, RIPK1 functions like an umpire in cells, making the tough calls necessary to balance competing signals that determine if cells live or die.

RIPK1 is already the focus of research to develop drugs that limit cell damage following heart attack, stroke or kidney injury. This study suggests the enzyme and the signals it helps to control might be harnessed to kill cancer cells. The results also provide clues about how the disease-fighting immune system curbs the spread of infection.

“This study fundamentally changes the way we think about RIPK1, a molecule that we care about because it is required for life,” said the study’s corresponding author Douglas Green, PhD, St. Jude Immunology chair.

The research appears in the scientific journal Cell.

St. Jude ranked as the No. 1 preferred company to work for by millennials

St. Jude is ranked as the top place students and young professionals wish to work, according to a survey conducted by the National Society of High School Scholars. This is the second year in a row that the hospital leads in the survey.

More than 12,000 high school students, college students and young professionals, ages 15–27, were asked to rank their preferred companies to work for from a list of 220 organizations.

The list of organizations on the survey are generated from FORTUNE magazine’s “100 Best Companies to Work For” and “Global 500” lists, DiversityInc’s “Top 50 Companies for Diversity” list and write-in choices. St. Jude has been on FORTUNE magazine’s “100 Best Companies to Work For” list for four consecutive years.

New twist discovered in Lou Gehrig’s disease

In 1939, a star hitter for the New York Yankees was diagnosed with a rare and deadly disease. The disease, amyotrophic lateral sclerosis (ALS), attacked his nerve cells, gradually weakening his muscles. Two years after ending Lou Gehrig’s baseball career, ALS took his life.

ALS remains incurable, but new insight into its causes gives reason to hope. A research team led by St. Jude revealed that mutations causing ALS have an unexpected toxic effect in human nerve cells.

Investigators found that mutations in a protein called TDP-43 disrupt the delivery of critical factors to the points of contact between nerve cells and muscles. To make the discovery, the scientists developed a new way to track the factors in living human nerve cells.

The research, published in the journal Neuron, opens a novel avenue in the pursuit of treatments for ALS and related disorders such as Parkinson’s and Alzheimer’s diseases. The work was led by J. Paul Taylor, MD, PhD, St. Jude Cell and Molecular Biology chair.

Broken DNA is bad for the brain

DNA may be the cornerstone of life, but the molecule breaks all the time. To read DNA’s code or make more DNA, cells routinely nick and unwind the famous double helix using specialized enzymes. Free radicals and other stresses can also break DNA.

Usually, cells just repair the break and life goes on. But if repair processes fail, the damaged DNA can hurt cells and tissues. DNA damage has been linked to diseases such as cancer and neurodegenerative disorders.

Research from St. Jude has revealed an unexpected cause for the DNA damage in two rare childhood diseases of the brain. In models of these diseases, an enzyme used by cells to nick DNA becomes trapped in the molecule. Because of disease-associated defects in the normal repair process, the enzyme stays trapped, leading to permanent DNA damage.

“We are now working to understand how this newly recognized source of DNA damage might contribute to tumor development or age-related DNA damage in the brain that is associated with neurodegenerative disorders like Alzheimer’s disease,” said Peter McKinnon, PhD, of St. Jude Genetics.

The findings appear in the journal Nature Neuroscience.

Hathaway visits St. Jude

Academy Award-winning actress Anne Hathaway hugs St. Jude patient Tyler West during a recent visit to the hospital. Patients and siblings were treated to an advanced screening of her new animated film Rio 2, in which Hathaway voices the part of Jewel. Hathaway toured the hospital and also visited patients’ rooms. The actress is a longtime supporter of the hospital.

Abridged from Promise, Summer 2014

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