Research Highlights - Promise Summer 2013


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Genome project sheds light on childhood brain tumors
The St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project has identified mutations responsible for more than half of a subtype of childhood brain tumor that takes a high toll on patients.

Buoyed hope through collaboration
Hundreds of brightly colored butterflies dotted the skies over St. Jude April 18 to mark Ependymoma Awareness Day.

Eat and destroy
Cells in the immune system have ancient defense systems that allow them to “eat” and destroy pathogens in the body.

Bird flu: A new tool in the arsenal
St. Jude scientists recently led research that identified a new indicator to determine the risk that avian H5N1 influenza viruses pose to humans.

Survivors and renal cancer risk
Childhood cancer survivors are at increased risk of developing renal cancer as young adults.

Survivors’ Day 2013
Childhood cancer survivors are at increased risk of developing renal cancer as young adults.

Beam of Hope
About 300 employees from St. Jude, Children’s GMP, LLC, and ALSAC recently wrote inspirational messages to patients and families on beams that will become a permanent part of a new clinical and research building being erected on campus.

“Rheostat” helps T cells match response to threat
A properly functioning immune system is a lesson in balance, providing protection against disease without attacking healthy tissue.

Dyer named HHMI investigator
Michael Dyer, PhD, of St. Jude Developmental Neurobiology, is one of 27 scientists nationwide to be selected this year as a Howard Hughes Medical Institute (HHMI) investigator.


Genome project sheds light on childhood brain tumors

The St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project has identified mutations responsible for more than half of a subtype of childhood brain tumor that takes a high toll on patients. Researchers also found evidence the tumors are susceptible to drugs already in development.

The study focused on a family of brain tumors known as low-grade gliomas (LGGs). Nationwide, surgery alone cures only about one-third of patients with this tumor.

Using whole genome sequencing, researchers identified genetic alterations in two genes that occurred almost exclusively in a subtype of LGG called diffuse glioma. Together, the mutations accounted for 53 percent of the diffuse gliomas in this study. The findings appeared in the scientific journal Nature Genetics.

“This subtype of low-grade glioma can be a nasty chronic disease; yet, prior to this study we knew almost nothing about its genetic alterations,” said David Ellison, MD, PhD, Pathology chair, and the study’s corresponding author. The first author is Jinghui Zhang, PhD, Computational Biology.

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Butterfly release

Buoyed hope through collaboration

Hundreds of brightly colored butterflies dotted the skies over St. Jude April 18 to mark Ependymoma Awareness Day. Ependymoma is a rare cancer of the brain or spinal cord that strikes children and adults. The event was organized by the Collaborative Ependymoma Research Network Foundation (CERN), an organization designed to better understand and speed advances against ependymoma. St. Jude leads CERN’s pediatric studies, and MD Anderson Cancer Center leads the adult studies. “Our collaboration with CERN is a natural extension of St. Jude’s cornerstone philosophy to freely share research and discoveries as a means to advance cures worldwide,” said Richard Gilbertson, MD, PhD, Comprehensive Cancer Center director and co-principal investigator of CERN.

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Eat and destroy

Cells in the immune system have ancient defense systems that allow them to “eat” and destroy pathogens in the body. Now, St. Jude scientists have evidence that a process that allows cells to quickly switch from “eating” mode to “destroying” mode might offer a new approach for taming the misguided immune response at the heart of autoimmune diseases.

The process allowing the switching event, called LC3-associated phagocytosis (LAP), was identified in the laboratory of Douglas Green, PhD, Immunology chair, and first described in research previously published in Nature.

Now researchers have found that LAP may, in some circumstances, trigger inflammation and an inappropriate immune response. The latest findings were published recently in the journal Immunity.

The study showed LAP is involved in the cell signaling that unleashes production of type 1 interferons. These proteins help defend against viral infections; the proteins have also been linked to autoimmune diseases like system lupus erythematosus, which strikes children and adults. Such disorders occur when the immune system attacks healthy tissue.

“The finding raises the possibility that lupus patients might benefit from treatments that target the machinery of LAP,” Green said.

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Charles Russell, PhD, and Hassan Zaraket, PhD

Bird flu: A new tool in the arsenal

Hassan Zaraket, PhD (at left), and Charles Russell, PhD, of St. Jude Infectious Diseases recently led research that identified a new indicator to determine the risk that avian H5N1 influenza viruses pose to humans. The research could lead to improved influenza surveillance, more efficient vaccine production and new tools to ease the risk of a pandemic.

The H5N1 influenza virus—otherwise known as the “bird flu”—has sickened at least 620 people since 2000 and is responsible for at least 367 deaths. However, its global reach has been limited by the fact that the virus cannot spread efficiently from one person to another. Health officials fear that if the virus acquires that capability, it would lead to a pandemic and public health emergency.

“Our ultimate goal is to understand what makes one influenza virus grow and spread in birds versus another that is able to grow and spread in mammals,” Russell said. “Knowing the answer could aid efforts to identify and track high-risk H5N1 avian influenza viruses and better prepare for a possible pandemic.”

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Survivors and renal cancer risk

Childhood cancer survivors are at increased risk of developing renal cancer as young adults. Preliminary evidence from a St. Jude-led study points to several factors that may be connected to this increased risk, including kidney irradiation and treatment with platinum-based chemotherapy drugs.

Even though renal cancer is typically a disease of older age, research published in the Journal of the National Cancer Institute found unexpectedly high rates of the tumor among adult survivors who were treated for childhood cancers when they were less than 20 years old. The survivors were participants in the Childhood Cancer Survivor Study (CCSS), a multi-institutional cohort study led by St. Jude. The survivors had renal cancer at eight times the rate expected in the general population.

Carmen Wilson, PhD, and Greg Armstrong, MD, both of St. Jude Epidemiology and Cancer Control, led the research. They found evidence that survivors whose pediatric cancer treatment included cisplatin or kidney irradiation of 5 gray or more faced a nearly fourfold higher risk of being diagnosed with renal cancer later.

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Hill Harper

Survivors’ Day 2013

Hundreds of St. Jude survivors will return to St. Jude for the 15th annual Survivors’ Day Conference, September 6–7. The keynote speaker is actor, author and cancer survivor Hill Harper (pictured above). The event will also feature a panel of childhood cancer survivors. Join the live webcast; details are available at stjude.org/survivors-2013.

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Beam of Hope

Beam of hope

About 300 employees from St. Jude, Children’s GMP, LLC, and ALSAC recently wrote inspirational messages to patients and families on beams that will become a permanent part of a new clinical and research building being erected on campus. With construction on the project taking place just yards away, employees penned well wishes, thoughts and prayers on the beams. The signing was intended to be a permanent gift of love for patients and their families, surrounding them with wishes for good health and happiness incorporated into the building.

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“Rheostat” helps T cells match response to threat

A properly functioning immune system is a lesson in balance, providing protection against disease without attacking healthy tissue. Work led by St. Jude scientists and published recently in Nature Immunology has identified a mechanism that helps components of the immune system called T cells find that sweet spot where the strength of the immune response matches the threat.

T cells use a variety of weapons to combat cancer and viral infections. “T cells are a double-edged sword, capable of launching a fierce attack to defeat an infection but also wreaking havoc if the response is too robust and results in damaging healthy tissue,” explained the paper’s senior author, Dario Vignali, PhD, Immunology vice chair.

Receptors embedded in the T cell membrane serve as a communication channel that enables the T cell to match its response to the threat. The researchers found that part of the T cell receptor functions like a rheostat, helping to regulate the sometimes explosive production of new T cells called proliferation.

The finding offers important insight into the immune response. The work also lays the foundation for advancing our understanding and treatment of problems that arise when the system malfunctions. For example, autoimmune disorders can occur when the immune system mistakenly targets healthy tissue, whereas an insufficient immune response can lead to chronic infectious diseases or cancer.

“These findings suggest how T cell receptors help to manage the response and possibly guard against complications resulting from an overly aggressive response,” Vignali said.

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Michael Dyer, PhD

Dyer named HHMI investigator

Michael Dyer, PhD, of St. Jude Developmental Neurobiology, is one of 27 scientists nationwide to be selected this year as a Howard Hughes Medical Institute (HHMI) investigator. The third HHMI investigator currently working at St. Jude, Dyer is an expert in the fields of developmental neurobiology, cell cycle regulation, stem cell biology, developmental therapeutics and cancer genetics.

“Being selected as an HHMI investigator is a great honor for any scientist, and the additional funding it provides will accelerate Dr. Dyer’s research and the impact he is having on the treatment of childhood cancers,” said Dr. William E. Evans, St. Jude director and CEO.

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Abridged from Promise, Summer 2013

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