Ephrins regulate stem cell proliferation following TBI

Project: Research project

Description

DESCRIPTION (provided by applicant): Five million Americans are presently living with disability as a result of traumatic brain injury (TBI). The majority of TBI research focuses on the factors that influence the onset of pathology, while fewer studies have addressed the mechanisms that promote recovery. Cellular loss associated with TBI is significant barrier to overcome, and recent advancements in stem cell transplantation and cellular rejuvenation provide a potential therapy for recovery. However, the mechanisms that regulate stem cell functions are still ill defined, and even less is known how the functions are altered following TBI. The studies outlined in this proposal will examine a family of molecules, Ephrins and their receptors (Eph receptors), which have been implicated throughout the developing CNS. We have recently demonstrated that these molecules are also expressed in adult stem/progenitor cell, adult neuroblasts and in surrounding tissues. We hypothesize that ephrinB3 may function to arrest cell cycle and in turn promote post-mitotic differentiation. Furthermore, following injury the over expression of ephrinB3 and/or its receptors may limit the ability of endogenous stem/progenitor cell to proliferate. We will employ gene-targeted knockout mice to investigate their functions within the subventricular zone (SVZ). Aim 1 of this application will investigate their function in regulating endogenous adult stem/progenitor cell proliferation in the SVZ, and whether the absence of ephrinB3 can alter cell cycle protein concentrations. Aim 2 will employ an in vitro assay to examine the mechanisms of action for ephrinB3 and signaling pathways used to regulate cell cycle arrest. Aim 3 will examine the role of ephrinB3 and its Eph receptor(s) in controlling cell proliferation following TBI. These studies will provide essential mechanistic information on the function of ephrinB3 and its receptor(s) to regulate stem/progenitor cell proliferation in the normal and injured brain, and could lead to therapeutic treatments to promote recovery in the chronically injured patient.
StatusFinished
Effective start/end date7/1/041/31/16

Funding

  • National Institutes of Health: $334,688.00
  • National Institutes of Health: $334,688.00
  • National Institutes of Health: $334,688.00
  • National Institutes of Health: $305,827.00
  • National Institutes of Health: $296,958.00
  • National Institutes of Health: $331,341.00
  • National Institutes of Health: $296,958.00
  • National Institutes of Health: $325,096.00
  • National Institutes of Health: $296,958.00
  • National Institutes of Health: $322,974.00

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Ephrins
Stem Cells
Cell Proliferation
Lateral Ventricles
Neurogenesis
Neural Stem Cells
Adult Stem Cells
Wounds and Injuries
EphB3 Receptor
Cell Cycle Checkpoints
Traumatic Brain Injury
EphA4 Receptor
EphA1 Receptor
Eph Family Receptors
Rejuvenation
Survival
Organized Financing
Cell Cycle Proteins
Gene Knockout Techniques
Aptitude

ASJC

  • Medicine(all)
  • Neuroscience(all)