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Julie Shen, PhD

Recessively inherited mutations in the parkin gene are a major cause of juvenile- or early-onset familial Parkinson's disease, which is caused by the loss of dopamine-producing neurons in the brain. In order to study this process in the laboratory, we have generated mutant mice lacking functional parkin. We propose to determine whether dopamine-producing neurons derived from the mutant mice or from mouse embryonic stem cells are more likely to degenerate in the absence of parkin protein. In addition, we propose to screen for drugs that increase the amount of normal parkin with the hope that these drugs can protect the dopamine-producing neurons from environmental stresses suspected of causing Parkinson's disease. Lastly, we propose to use the newly developed gene chip technology to search for other genes that are regulated by parkin, which might be effective therapeutic targets for Parkinson's disease.

Dr. Jie Shen received her PhD in molecular biology from the University of Virginia in 1995. As a graduate student in Dr. Jay Hirsh's laboratory, she took advantage of the sophisticated genetic approaches available in Drosophila to study the mechanisms of alternative splicing of the dopa decarboxylase gene, which encodes a key biosynthetic enzyme for neurotransmitters such as dopamine. In the hope that her research efforts might benefit humanity more directly, Dr. Shen decided to apply her background in molecular biology and genetics to the study of neurologic disease. As a postdoctoral fellow in the laboratory of Dr. Susumu Tonegawa at MIT, she began by studying the molecular basis of Alzheimer's disease (AD), focusing her efforts on presenilin-1 (PS1), the major gene product responsible for familial AD. Through the generation and analysis of knockout mice that lack PS1 function and transgenic mice that overexpress familial AD-linked mutant forms of PS1, Dr. Shen obtained the first evidence regarding the normal function of PS1 in vivo. Her findings demonstrated a critical role for PS1 in the regulation of CNS development, neurogenesis and Notch signalling. In 1998, Dr. Shen established her independent laboratory in the Center for Neurologic Diseases at the Brigham and Woman's Hospital and Harvard Medical School, where she is currently assistant professor and a member of the Program in Neuroscience. Her laboratory's primary interest is the normal function of gene products linked to familial AD and Parkinson's disease (PD), and the mechanisms by which alterations in their function cause neurologic disease. Her research has particularly focused on the presenilins and parkin, combining advanced mouse genetic technologies with biochemical, cell biological and behavioral approaches to understand their roles in brain development and function and neurodegeneration.

Associated Grants

  • Rapid Parkinson's Drug Screen Using Parkin Knockout Stem Cells


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