The Short and Long-term Effects of Biological Agents on Oligodendrocyte Lineage and Progenitor Cells in Developing Brain


The short and long-term effects of biological agents on oligodendrocyte lineage and progenitor cells in the developing brain

PI:  Joseph Scafidi, DO – Children’s Research Institute, Washington, DC

(update on progress)  Grant duration, Aug. 2011--Sept. 2013


The brain of children is subject to rapid growth and development. White matter is the part of the brain that is vital for communication and processing of information. White matter comprises nearly half of the human brain, and its growth and    development occurs specifically after birth and continues throughout childhood. During this critical period of white matter maturation, it is vulnerable to drugs or other agents that affect its proliferation and growth and can result in injury. Injuries to the white matter lead to life-long cognitive and sensori-motor delays.


Children diagnosed with brain tumors are treated with combination therapies, which often include chemotherapy, radiation and specific targeted biological therapeutic agents, which are aimed at arresting tumor growth. The same pathways involved in uncontrolled tumor growth are part of complex mechanisms imperative for normal white matter growth and maturation. Using a multidisciplinary approach, the Scafidi laboratory is studying how these specific targeted biological agents affect  normal white matter development at different developmental ages. Specifically, their studies are focused on the cellular, biochemical and  behavioral effects these agents have on the developing brain and whether its effects are developmentally age specific.   Understanding the effects these agents have on the developing brain will further our knowledge of normal brain   development and the long-term consequences of these drugs.  (Oral presentations were made at two international meeting regarding this research.)


Sincere appreciation to the Childhood Brain Tumor Foundation for its dedication to funding vital research initiatives!      



The Short and Long-term Effects of Biological Agents on Oligodendrocyte Lineage and Progenitor Cells in Developing Brain (new, first-year)

PI:  Joseph Scafidi, DO, Children’s Research Institute


Childhood is a critical time because of rapid growth and development of the brain. During this period, the brain’s white matter, composed of myelin, is the last structure to fully mature. There is growing evidence that a disturbance in white matter development contributes to significant developmental delays. There is a large gap in knowledge in how newer molecularly   targeted therapies used to treat pediatric brain tumors affect brain development, specifically white matter, during this critical period. This study, using a multidisciplinary approach, will assess and characterize the effect newly developed molecularly   targeted agents have on myelin producing cells and determine whether this is dependent on developmental stage of the brain. This study will provide a better understanding of white matter development and establish new methods to assess the effects these therapies have on the developing brain.

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