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Two UCSF Researchers Awarded Funding for Work on Pediatric Oncology

UCSF's Adam de Smith, PhD, has received $450,000 in research funding to study the role of genetic and epigenetic variation in risk of childhood acute lymphoblastic leukemia in Down syndrome.

Two UC San Francisco faculty members are among three promising young researchers nationally recognized for their work in pediatric oncology. UCSF’s Adam de Smith, PhD, and Kyle Walsh, PhD, will share a $1.35 million award with Duke University’s Lisa Crose, PhD.

The funding comes from Alex’s Lemonade Stand Foundation (ALSF), a nonprofit organization dedicated to finding cures for childhood cancers. Its three ‘A’ Awards will provide each recipient $450,000 over three years to further their work. De Smith plans to examine acute lymphoblastic leukemia (ALL), Walsh will study osteosarcoma, and Crose’s research interest is rhabdomyosarcoma.

“I truly feel honored to have been selected for this award from such a prominent childhood cancer charity,” said de Smith, an assistant professional researcher in the UCSF School of Medicine’s Department of Epidemiology & Biostatistics. “It is also the first research grant that I have received in my academic career to date, and it will enable me to carry out a comprehensive and unique investigation into the causes of acute lymphoblastic leukemia in children with Down syndrome.”

Acute lymphoblastic leukemia is the most common childhood cancer, and children with Down syndrome have an approximately 20-fold increased risk of developing ALL, as well as higher rates of relapse and treatment-related mortality than children without Down syndrome. De Smith hopes that by understanding the causes of ALL in children with Down syndrome, this might lead to earlier detection and better treatment of this disease, as well as shedding light on the etiology of ALL in the general population.

“This ALSF 'A' Award will provide an invaluable source of funding that will hopefully help me to establish my own research lab here at UCSF, with a particular focus on identifying risk factors for childhood leukemia,” de Smith said.

Kyle Walsh, PhD

Walsh, the co-award recipient from UCSF, hopes that by investigating genetic factors with a particular focus on those genes known to contribute to human height, he can decipher key elements about the underlying biology of osteosarcoma initiation.

"Alex's Lemonade Stand Foundation has a rich history of funding high-impact pediatric oncology research," said Walsh, assistant professor in residence of neurological surgery and epidemiology and biostatistics in the UCSF Department of Neurological Surgery. "I am excited to join the ranks of previous award recipients and I look forward to using the funding to investigate osteosarcoma etiology. Children who are tall for their age are at greatly increased risk to develop osteosarcoma, a malignant bone cancer."

The ‘A’ Award joined a prestigious line of medical and nursing grants from Alex’s Lemonade Stand Foundation in 2009 to encourage the best and brightest young researchers to build lifelong careers in the field. Operating under the belief that engaging researchers early in their career leads to a long term commitment to find a cure, ALSF works to find and support exceptional early-career researchers.

Along with the funds provided to ‘A’ Award recipients ($150,000 per year for three years), the award will also include the opportunity to speak and attend Foundation events, reference books to enhance the researchers’ personal pediatric oncology libraries, equipment to aid in their research (up to $10,000 value) and funding to attend one educational course or event.

“Since the time our daughter battled cancer over ten years ago, we have been keenly aware of how important the fresh perspectives of young investigators are to finding better treatments and cures for kids with cancer,” said Jay Scott, co-executive director of Alex’s Lemonade Stand Foundation. “The ‘A’ Awards play an integral role in doing just that, allowing young scientists with original projects the space and time to follow through with promising research.”

The ‘A’ Award joined a prestigious line of medical and nursing grants from Alex’s Lemonade Stand Foundation in 2009 to encourage the best and brightest young researchers to build lifelong careers in the field. Operating under the belief that engaging researchers early in their career leads to a long term commitment to find a cure, ALSF works to find and support exceptional early-career researchers.

Specific Areas of Interest

Adam de Smith, PhD

Investigating the Role of Genetic and Epigenetic Variation in Risk of Childhood Acute Lymphoblastic Leukemia in Down Syndrome

Background

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. Down syndrome (DS) is a genetic disorder caused by an extra chromosome 21, and DS children have a 20-fold increased risk of ALL. Furthermore, children with ALL and DS ("DS-ALL") have increased treatment-related deaths and disease recurrence than children without DS. Determining the cause of DS-ALL is, therefore, of paramount importance. The additional chromosome 21 must play a role in increased leukemia risk, but not every child with DS develops ALL. We predict that additional variations may affect DS-ALL risk.

Project Goal

Adam de Smith, PhD

This study is designed to discover why some children with DS contract leukemia while others do not. We will analyze genetic variation in DS-ALL children compared to DS children without ALL, specifically by investigating single base DNA changes as well as "copy number variation," that is, deleted or duplicated sections of DNA. This will be carried out across the genome, with a special focus on chromosome 21. We will also determine whether genetic variations are associated with ALL risk in children without DS, in a set of ALL cases and controls. Furthermore, we will assess how modifications of DNA expression that can turn genes on or off, so-called "epigenetic" changes, may affect DS-ALL risk.

This will be the first comprehensive investigation of the role of genetics and epigenetics in risk of DS-ALL, and will lead to earlier risk stratification and potentially improved treatment of this disease, as well as shedding light on the causes of ALL in all children.

Kyle Walsh, PhD

Genetic Susceptibility to Pediatric Osteosarcoma and Interaction with Measures of Childhood Growth

Background

Osteosarcoma rates increase with age until puberty, at which point risk declines markedly. Pediatric osteosarcoma is associated with increased birth weight, taller stature and male gender. Biological pathways related to childhood growth and development likely play an important role in the development of osteosarcoma, but congenital causes remain poorly understood.

Project Goal

Kyle Walsh, PhD

By leveraging a large multi-ethnic patient population drawn from the California Birth Cohort, we will compare the genomes of 545 children with osteosarcoma to the genomes of 3545 cancer-free individuals to identify genetic risk factors underlying this disease. Because this study utilizes biologic specimens collected at birth, years prior to diagnosis, its powerful design enables identification of potential biomarkers of future osteosarcoma risk. In addition to studying the heritable causes of osteosarcoma, we also seek to identify genetic variants that are associated with poor prognostic factors, such as larger tumor size and presence of distant metastases. An enhanced understanding of the factors underlying pediatric osteosarcoma risk, including how genetic variation interacts with childhood growth trajectories and clinical prognosis, could help detect susceptible populations and identify children with potentially aggressive tumor behavior. By conducting a truly multi-ethnic study, conducted within the diverse population of children born in California since 1989, we will extend pediatric osteosarcoma research to include populations frequently omitted from cancer studies. We expect discoveries from our proposed investigation to profoundly change osteosarcoma research paradigms and to usher in a new generation of genomic studies that can improve outcomes for children affected by this devastating disease.

For more information on the ‘A’ Award, or Alex’s Lemonade Stand Foundation’s various grant categories and successes, visit www.ALSFgrants.org

Content from Alex's Lemonade Stand Foundation were used in this announcement.

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