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Stephen Davies, PhD

Associate Professor


 

Graduate School and Center Affiliations:

Member, UCD Graduate Faculty
Neurosciences Graduate Program
Biomedical Sciences Program

Education:

    • Ph.D. - Neurobiology, Nervous System Regeneration, University College London / National Institute for Medical Research, Mill Hill, UK 1991-1996

Postdoctoral Fellowship:

    • Division of Neurobiology, National Institute for Medical Research, Mill Hill, London, UK, 1996-1997
    • Department of Neurosciences, Case Western Reserve University, Cleveland, USA, 1997-2000

Previous Faculty Appointments:

    • Departments of Neurosurgery and Neuroscience, Baylor College of Medicine, Houston, Texas 2000-2007

Davies Lab

    • Jeannette Davies Ph.D. (Assistant Professor)
    • Kenneth Minor Ph.D. (Instructor)
    • Suzanne Green MS (PRA)
    • Kyle Jasper BS. (PRA)
    • Matthew Perry-Light (Medical Student – MSRT program)
    • Veronica Parra-Mendoza (Undergraduate – LABCOATS program)

Regeneration of the Adult Central Nervous System.

 Image: Specific subtypes of astrocytes generated by exposing glial precursor cells to BMP (GDA BMP) or CNTF (GDA CNTF).

The primary focus of our research is the development of new, effective therapies for the injured or diseased central nervous system (brain and spinal cord: CNS) with a particular emphasis on treatments for traumatic spinal cord injury.

Stem cell based cell replacement therapies for the CNS have received a great deal of recent attention, however most researchers have concentrated on the replacement of damaged neurons and oligodendrocytes (axon ensheathing cells). Relatively little attention has been given to the replacement of astrocytes, despite the fact that astrocytes are one of the most prevalent cells in the adult human brain and spinal cord. Recent studies have shown that astrocytes ("star cells") actually control: 1: axon (nerve fiber) sprouting, 2: the growth of dendrites (the cell processes on neurons that receive signals from axons), 3: development of new connections between neurons (called synapses) and 4: the transmission of signals between neurons at synapses. In light of these new insights into astrocyte biology it is readily apparent that astrocyte replacement should be a major goal of stem cell based therapies for the injured or diseased brain and spinal cord.

Working in collaboration with University of Rochester, NY, our research team has developed a novel technology that allows us for the first time to make specific subtypes of astrocytes from embryonic multi-potent stem cells called glial restricted precursor cells (GRP cells). We have named one specific type of highly beneficial stem cell derived astrocyte - GRP derived astrocytes BMP or GDAs BMP, so called because they are derived from GRP cells treated with bone morphogenetic protein (BMP). Adult spinal cord injured rats treated with GDAsBMP showed ~40% in just 8 days and had returned to pre- injury scores in tests of brain control of limb movement by 2 to 4 weeks after treatment (1). In addition the GDAs BMP cells were also able to provide robust protection of injured neurons in the brain and spinal cord, a result that has important implications for treating stroke, ALS, Parkinson's and Alzheimers disease.

Our spinal cord injury studies highlight the importance of controlling the fate of stem cells to achieve optimal tissue repair as "naïve" GRP stem cells or another subtype of astrocyte generated by treating GRP cells with ciliary neurotrophic factor -GDAs CNTF - not only failed to promote functional recovery when transplanted into injured spinal cords but also cause pain syndromes, a severe side effect that was not seen in rats treated with GDAs BMP(2). In our latest study published in PLoS ONE and conducted in collaboration with University of Rochester, NY, we have generated the human form of the GDAs BMP cells and shown that transplantation of these specific human astrocytes can also promote robust functional recovery, axon growth and protection of spinal cord neurons in spinal cord injured rats (3). Our research team is now working to translate human GDAs BMP to use in treating human brain and spinal cord injuries.

Recent relevant publications:

    1. Davies J.E., Huang C.X., Proschel C., Noble M., Mayer-Proschel M. and Davies S.J.A. (2006) Astrocytes derived from glial restricted precursors promote spinal cord repair Journal of Biology 5:7. (Online Open Access http://jbiol.com/content/5/3/7)
    2. Davies J.E., Proschel C., Zhang N., Noble M., Mayer-Proschel M. and Davies S.J.A (2008) Transplanted astrocytes derived from BMP or CNTF treated glial restricted precursors have opposite effects on recovery and allodynia after spinal cord injury. Journal of Biology 7:24 (Online Open Access http://jbiol.com/content/7/7/24)
    3. Davies S.J.A., Chung-Hsuan S., Noble M., Mayer-Proschel M. Proschel C and Davies J.E (2011) Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury. PLoS ONE (online) http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017328