Developmental Neurobiology

Brain Tumour Foundation of Canada, in collaboration with the National Brain Tumour Society is proud to announce the 2011 Developmental Neurobiology Grant Awardees

  • Robert Wechsler-Reya, PhD Sanford-Burnham Medical Research Institute, La Jolla, CA
    Genetic targeting of cerebellar stem cells to study development and tumorigenesis

    Project description: One of the most aggressive forms of medulloblastoma are called MYC driven tumors (they have an overexpression of the c-MYC oncogene). They are suspected to originate from brain tumor stem cells, but further testing is required to be certain. This project will develop mouse models to determine whether stem cells can give rise to MYC-driven medulloblastoma and then explore the finding to develop new therapies

  • Alexandra Joyner, PhD Memorial Sloan-Kettering Cancer Center, New York, NY
    Identification of genes and cell behaviors regulated by Shh/Gli2 signaling in the cell of origin of a major subtype of medulloblastoma using novel genetic tools in mouse

    Project description:The project will investigate a subtype of medulloblastoma that effects signaling in the hedgehog (HH) pathway. The hedgehog pathway plays an important role in the developing brain. Currently, not enough is known about the progenitor cells (cells of origin) and critical genes regulated by the hedgehog pathway to allow us to control it in a way that does not compromise the development of the child. Joyner will investigate the effect of hedgehog signaling on cells that develop into tumors and identify the genes involved to create drug targets for new therapies.
  • Joseph Scafidi, DO Children's Research Institute, Washington, DC
    The effects of molecularly targeted therapies on the developing neurogenic niches

    Project description: New therapies are being developed that target pathways contributing to tumor development and growth. While the new agents show promising results against the tumor, there is concern that they are targeting pathways important in normal brain development. This study will look at how these targeted therapies effect the developing brain at different developmental time points, explore the brains ability to recover, and the influence of rehabilitation therapy on the brain.

    Medulloblastoma is the most common developmental brain tumor. The quality of life for survivors is compromised by the harsh side effects of current treatments. Medulloblastomas are divided into subtypes based on the expression of key developmental genes. The two projects listed below explore two different subtypes of medulloblastoma.

Purpose of the Partnership and Projects:

The discovery and development of effective therapies for pediatric brain tumors that significantly prolong the lives of patients but that do not have long-term adverse effects is a formidable challenge. While the life expectancy prognosis for some pediatric brain tumors is dismal, great therapeutic strides have been made with others through the use of effective interventional surgery, radiotherapy and chemotherapy.

These survival rate strides have not come without their detrimental costs to the patients and their families. Long-term survivors of pediatric brain tumors generally display what are referred to as late effects from their treatments. These include severe cognitive (e.g. thinking, problem solving, reasoning, decision-making, attention, memory), psychosocial (e.g. behavioral, emotional, social adjustment), and endocrine (i.e. hormonal) deficits which may not manifest for years following tumor diagnosis and treatment, but which are chronic and progressive. This is referred to as “growing into deficit.” General intellect as measured by IQ declines and that decline significantly increases with time. Deficits often result in academic failure and inability for adolescents to graduate from high school. As patients become adults, their deficits affect their ability for employment, their incomes, their ability for independent living, the likelihood they will marry, their emotional health and overall quality of life.

Pediatric brain tumors arise as the result of normal brain developmental processes gone wrong. Conversely, pediatric brain tumors and their treatment adversely effect the normal brain development that continues postnatally through infancy, childhood, adolescence and into adulthood. Developmental neurobiology is the field of study of normal brain development and function, and can be instrumental in the understanding of the genesis of brain tumors and the cells from which brain tumors arise. This understanding will enhance the ability to discover effective therapeutic approaches to pediatric brain tumors.

The evaluation of the effect of newly discovered therapeutic approaches, as well as established approaches and their modifications, on the continuing normal development of the brain is critical to determining the potential adverse effects of therapies on that normal brain development.

Developmental neurobiology is an investigational link that ties together and balances these essential components of pediatric brain tumor research that are required for the discovery and development of effective brain tumor therapies with minimal adverse effects on the brain’s continuing normal development.



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