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2008 NREF/Pinnacle Partners in Neurosurgery Research Grant
Rahul Jandial, MD
University of California San Diego Medical Center
Role of the gene MELK in neural stem cell proliferation
Stem/precursor cells hold great promise for cell replacement therapies and regenerative medicine, but their clinical success will depend on our ability to control their self-renewal and differentiation. MELK is a gene that may modulate proliferation in neural precursors and is found in the subventricular zone of MELK-EGFP promoter-reporter transgenic mice.
We intend to investigate the molecular mechanisms that regulate neural stem cell proliferation and self-renewal. To do this we will evaluate the proliferative capacity and cell fate of MELK/EGFP-positive cells isolated from our transgenic animals via transplantation assays and determine if these cells from the neonatal pup subventricular zone are proliferating neural precursors in vivo. Subsequently these cells will be evaluated in vitro with siRNA and cDNAs for assessment of proliferative capacity at variable levels of MELK gene product, as well as investigate the involvement of putative MELK targets and their effects on proliferation and self-renewal.
By understanding self-renewal and the role MELK plays, we would provide avenues for potential modulation of neurogenesis dependent on MELK expression. Further, synthetic agonists of MELK could be used to modulate the amplification of neural progenitors for clinical application.
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