Research Highlights - Promise Spring 2014

New clues for fighting Alzheimer’s disease

St. Jude scientists have made a surprising connection between a rare disorder that strikes young people and Alzheimer’s disease, a disease that usually affects older adults. The connection is an enzyme that nerve cells use to recycle or dispose of unneeded proteins. Young people with the disorder sialidosis have too little enzyme. A recent study suggests the enzyme might also play a role in Alzheimer’s disease.

Individuals with Alzheimer’s disease develop plaques in their brains made of abnormal clumps of protein. In laboratory studies, St. Jude researchers found that increasing enzyme activity may reduce the number of plaques in the brain. The research was led by Alessandra d’Azzo, PhD, of St. Jude Genetics (center), who is pictured with colleagues Ida Annunziata, PhD (at left), and Annette Patterson (at right). The research appeared in the scientific journal Nature Communications.

“This is the first time this enzyme has been linked to Alzheimer’s disease. We hope it will lead to better tools to diagnose as well as slow, or even reverse, the disease in some patients,” d’Azzo said.

Taking aim at a global killer of kids

Antibiotic resistance is a growing global concern, especially in bacteria that cause serious diseases, such as tuberculosis (TB). This disease kills 1.3 million people a year, and extremely drug-resistant TB has been reported in dozens of countries.

St. Jude scientists recently led a project to re-engineer an existing weak antibiotic into a TB killer. Chemical changes to the original drug prevent TB bacteria from flushing the new antibiotic out of their system.

The new antibiotics work well against drug-resistant TB, and appear to be safe and effective in laboratory studies.

“We are now working towards the next key step: testing these antibiotics in a clinical trial of patients with drug-resistant TB,” said Richard Lee, PhD, of St. Jude Chemical Biology and Therapeutics.

The findings were reported in Nature Medicine.

Good FORTUNE

For the fourth consecutive year, St. Jude has made FORTUNE magazine’s list of the “100 Best Companies to Work For.”

The list recognizes companies with exceptional workplace cultures that foster high employee morale and dedication. Companies are graded based on employee surveys and questionnaires about company programs and practices. St. Jude employees give particularly high ratings to their pride in working for the hospital and their ability to make a difference.

“This recognition not only serves to inspire all of us who work here every day; it also helps us recruit and retain the very best people,” said Dr. William E. Evans, St. Jude director and CEO.

More than 252,000 employees at 257 companies participated in the most recent survey.

Stressing cancer out

Even cancer cells can feel stress. In fact, it can kill them. According to new research led by St. Jude, drugs that enhance a process called oxidative stress may offer a new way to combat an aggressive soft tissue tumor called rhabdomyosarcoma.

Clues hidden deep within the DNA of tumor genomes suggested that rhabdomyosarcoma cells may experience high levels of oxidative stress. To exploit this potential weakness, the researchers used drugs to boost the levels of oxidative stress still higher. The tumor cells died.

“This suggests that altering the ability of tumor cells to handle that stress—or increasing the stress just a bit—is enough to push the cell over the edge, and it dies,” said Michael Dyer, PhD, of St. Jude Developmental Neurobiology, who is a Howard Hughes Medical Institute investigator. “This gives us novel and exciting new therapeutic options to pursue.”

The research also revealed that two key types of childhood rhabdomyosarcoma have different underlying genetic causes and provided insights into why tumors sometimes come back after treatment. The findings, published in Cancer Cell, are the latest emerging from the St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project.

Sherr inducted into American Academy of Arts and Sciences

Charles Sherr, MD, PhD, St. Jude Tumor Cell Biology chair, and Howard Hughes Medical Institute Investigator, signs the American Academy of Arts and Sciences’ Book of Members during an induction ceremony in Cambridge, Massachusetts. Sherr was among 164 of the nation’s most influential artists, scientists, scholars, authors and institutional leaders who were inducted into the American Academy of Arts and Sciences. Founded in 1780 by John Adams, the academy is one of the nation’s oldest and most prestigious learned societies, and an independent research center that draws from its members’ expertise to conduct studies in science and technology policy, global security, the humanities and culture, social policy, and education.

Waking up the body’s defense system

Blood contains a large number of T cells, which act like soldiers that defend against infections and other invaders. When T cells detect a threat, they “wake up” and start multiplying into an army to destroy it. How T cells are triggered to multiply has been largely a mystery.

St. Jude scientists have solved a central piece of the puzzle: T cells become fully awake thanks to the actions of a specific protein complex. Named mTORC1, this complex instructs T cells to start burning sugar and making lipids. These metabolic activities prompt the T cells to start multiplying into the army that fights an infection.

“Our results answer a long-standing question about how one branch of the immune system is called into action at the first sign of an infectious disease,” said Hongbo Chi, PhD, of St. Jude Immunology. “Our data show that T cell metabolism could be targeted for therapeutic benefit in the treatment of asthma and other diseases.” The findings appear in the journal Immunity.

Learning more about cognitive deficits

New research led by St. Jude scientists indicates that the academic struggles of some brain tumor survivors may be due to damaged “insulation” covering nerve cells in the brain. The damage may be caused by either the disease or its treatment.

The speed at which some medulloblastoma survivors process information declines dramatically following diagnosis and treatment of the brain tumor. Researchers found that patients’ working memory and broad attention were less affected.

Results reinforce the importance of working closely with families and teachers to ensure survivors have the support and resources necessary to succeed. St. Jude researchers are also testing approaches to slow or prevent cognitive declines.

The research, led by Amar Gajjar, MD, St. Jude Oncology co-chair, and Shawna Palmer, PhD, formerly of Psychology, was published in the Journal of Clinical Oncology.

Abridged from Promise, Spring 2014

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