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Steven G. Kernie, M.D.
Associate Professor of Pediatrics and Developmental Biology
Integrative Biology
Office: (214) 648-4183
Fax: (214) 648-1960
Building ND, Room 5.120
Email: Steven.Kernie@UTSouthwestern.edu
The presence of adult neural stem and progenitor cells in the mammalian brain has awakened new interest and optimism in potential treatment for a variety of acquired brain disorders. It is, however, unclear what role, if any, adult neural stem cells play in contributing to post-injury recovery. We are interested in defining how adult neural stem and progenitor cells participate in injury-induced remodeling and in identifying genes that might be important in augmenting their contribution.
The hippocampus is central to the formation of memory and has recently been implicated in higher cognitive functioning as well. In all mammals, the one area of the hippocampus that has constant neuronal turnover due to a persistent population of neural stem and progenitor cells is the dentate gyrus. The dentate gyrus functions to integrate cortical input and transmit this to other areas of the hippocampus. We study how the dentate gyrus develops and responds to injury such as trauma and hypoxia at varying ages.
In order to do this, we have taken a genetic approach in mice that allows us to trace stem and progenitor cells within the hippocampus and gives us the ability to perform temporally specified genetic changes. We have developed a variety of tools to do this including tetracycline, tamoxifen, and ganciclovir-based systems that allow for fate labeling, progenitor ablation, and temporally and spatially regulated genetic deletions. Moreover, the addition of fluorescent tags in these transgenics allows us to quantify the number of adult neural stem cells during development and activated by injury by utilizing fluorescent activated cell sorting (FACS). These models make up the foundation to our lab’s approach of understanding how neural stem and progenitor cells may contribute to recovery following acquired brain injury.
Awards & Honors
Elected Member, 2005.
Society for Pediatric Research
Annual Scientific Award, 2003.
Society for Critical Care Medicine 32nd Annual Congress.
Young Investigator Fellow Award, 2002.
Society for Critical Care Medicine 31st Annual Congress.
President’s Research Council Distinguished Young Researcher Award, 2000.
The University of Texas Southwestern Medical Center at Dallas.
Selected References
Yu TS, Zhang G, Liebl DJ, and Kernie SG. (2008) Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors. Journal of Neuroscience; 28(48). 12901-12912. PMID: 19036984
Chen Y*, Miles DK*, Hoang TN, Shi J, Hurlock EC, Kernie SG, and Lu QR. (2008) The bHLH transcription factor Olig2 is critical for reactive astrocyte proliferation after cortical injury. Journal of Neuroscience; 28(43). 10983-10989. * equal contribution. PMID: 18945906
Miles DK and Kernie SG. (2008) Hypoxic-ischemic injury activates early hippocampal stem/progenitor cells to replace vulnerable neuroblasts. Hippocampus; 18: 793-806. PMID: 18446826
Koch J, Miles DK, Gilley J, Yang CP, and Kernie SG. (2008) Brief exposure to hyperoxia depletes the glial progenitor pool and impairs functional recovery following hypoxic-ischemic brain injury. Journal of Cerebral Blood Flow and Metabolism; 28 (7). 1294-1306. PMID: 18334993
Chumley M, Catchpole T, Silvany R, Kernie SG, and Henkemeyer M. (2007) EphB receptors regulate stem/progenitor cell proliferation, migration, and polarity during hippocampal neurogenesis. Journal of Neuroscience; 49: 1381-1390. PMID: 18057206
Shi J, Miles DK, Orr BA, Massa SM, and Kernie SG. (2007) Injury-induced neurogenesis in Bax-deficient mice: Evidence for regulation by voltage-gated potassium channels. European Journal of Neuroscience; 25: 3499-3412. PMID: 17610570
Miles DM and Kernie SG. (2006) Activation of neural stem and progenitor cells after brain injury. Moller, Chapman, and Lombar, eds. Progress in Brain Research; 157(12). 187-97. PMID: 17167908
Shi, J, Parada LF, and Kernie SG. (2005) Bax limits adult neural stem cell persistence through caspase and IP3 receptor activation. Cell Death and Differentiation; 12: 1601-1612. PMID: 15947791
Yu T, Dandekar M, Monteggia LM, Parada LF, Kernie SG. (2005) Temporally regulated expression of Cre recombinase in neural stem cells. Genesis; 41: 147-53. PMID: 15789426
Salman H, Ghosh P, Kernie SG. (2004) Subventricular zone neural stem cells remodel the brain following traumatic injury in adult mice. Journal of Neurotrauma; 21(3): 283-92. PMID: 15789426
Kernie SG, Erwin TM, Parada LG. (2001) Brain remodeling due to neuronal and astrocytic proliferation following controlled cortical injury in mice. Journal of Neuroscience Research; 66(3): 317-26. PMID: 11746349
Kernie SG*, Liebl DJ*, Parada LF. (2000) BDNF regulates eating behavior and locomotor activity in mice. EMBO Journal; 19(6): 1290-1300. *equal contribution. PMID: 10716929
In the news:
Resuscitation technique after brain injury may do more harm than good, researchers find
