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Our research focuses on molecular and cellular interactions that control spinal cord development and regeneration after injury. At present, we studied the effects of neuronal migration errors found in the dorsal horn of the reel spinal cord. Reelin is a secretory glycoprotein that binds to lipoprotein receptors VLDLR and apoer2, is internalized and activates the tyrosine kinase cascade, which can phosphorylate intracellular adaptor protein disabled-1 (Dab1). Reelin signaling pathway regulates neuronal localization in the spinal cord in a cell-specific manner; Different subsets of neurons maintained migration errors, while other neurons were located correctly. Our laboratory found migration errors in the dorsal horn of reeler and Dab1 mutants during development and adults. Importantly, both reeler and Dab1 mutants showed increased sensitivity to heat and significantly decreased mechanical sensitivity. Our results show that neurons expressing reelin and Dab1 are important contributors to the normal development of basic circuits for thermal and mechanical pain processing.
The second focus of the laboratory is to study axonal regeneration after complete spinal cord transection. Together with Dr. Edgerton's laboratory in UCLA, we completed four extensive studies in which olfactory bulb derived olfactory ensheathing cells (OECs) were transplanted into the spinal cord after chest T8 level transection. We found that compared with control rats receiving culture medium or fibroblast transplantation, adult spinal cord rats transplanted with OEC had: 1) improved motor performance during treadmill walking of hind limbs, 2) motor evoked potential induced by transcranial electrical stimulation, which disappeared after re transection, and evidence of original injury, 3) regeneration of supraspinal cord and spinal cord noumenon, And 4) modification of the injury site, in which OEC is aligned with astrocytes to promote the growth of axons in the injury.
The second focus of the laboratory is to study axonal regeneration after complete spinal cord transection. Together with Dr. Edgerton's laboratory in UCLA, we completed four extensive studies in which olfactory bulb derived olfactory ensheathing cells (OECs) were transplanted into the spinal cord after chest T8 level transection. We found that compared with control rats receiving culture medium or fibroblast transplantation, adult spinal cord rats transplanted with OEC had: 1) improved motor performance during treadmill walking of hind limbs, 2) motor evoked potential induced by transcranial electrical stimulation, which disappeared after re transection, and evidence of original injury, 3) regeneration of supraspinal cord and spinal cord noumenon, And 4) modification of the injury site, in which OEC is aligned with astrocytes to promote the growth of axons in the injury.
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Patricia E Phelps,Sung Min Ha,Rana R Khankan,Mahlet A Mekonnen, Giovanni Juarez, Kaitlin L Ingraham Dixie,Yen-Wei Chen,Xia Yang
bioRxiv : the preprint server for biology (2023)
Spinal Interneuronspp.159-170, (2023)
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Luke Stuart Urban,Michael A Thornton, Katie L Ingraham Dixie,Erica A Dale,Hui Zhong,Patricia E Phelps,Joel W Burdick,V Reggie Edgerton
eNeurono. 3 (2019)
Griselda M Yvone, Hannah H Zhao-Fleming, Joe C Udeochu,Carmine L Chavez-Martinez,Austin Wang, Megumi Hirose-Ikeda,Patricia E Phelps
Rana R. Khankan,Khris G. Griffis, James R. Haggerty-Skeans,Hui Zhong,Roland R. Roy,V. Reggie Edgerton,Patricia E. Phelps
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