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Earl W. Godfrey

    • Title:
    • Professor

    • Role:
    • Faculty

    • Faculty Appointments:
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    • Focus Areas:
    • Neuromuscular disease (ALS)

      Molecular basis of synapse formation

      Stem Cells and Anti-inflammatory Therapy for ALS

      Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig’s Disease) is caused by degeneration of spinal cord motor neurons, resulting in progressive paralysis, usually leading to death within five years of diagnosis.  The underlying pathology is poorly understood, although aggregation of misfolded proteins is thought to play a major role in neuronal degeneration.  Stem cell transplantation into the spinal cord or muscles of rats carrying with a mutant human gene for superoxide dismutase (SOD1), an animal model of ALS, can slow disease progression, extend lifespan, and reduce motor neuron loss in ALS. Inflammation in the spinal cord also contributes to degeneration and death of motor neurons in ALS.  We hypothesize that inflammation will be reduced, motor neuron degeneration delayed, and lifetime extended by (1) transplantation of glial precursor stem cells into spinal cord of ALS model rats and (2) use of novel anti-inflammatory compounds in combination with stem cell therapy.  Stem cells are being transplanted into the spinal cords and/or muscles of G93A SOD1 mutant rats, to test their ability to reduce inflammation, neutralize the toxic environment in the spinal cord, and rescue motor neurons, extending the lifespan of the diseased animals.  Astrocytes (a type of glial cells) from ALS model mice secrete toxic factors that kill motor neurons in culture.  Reducing toxicity in the ALS spinal cord is critical for protecting these neurons and preventing degeneration of motor nerve connections to muscles.  It has recently been shown that inactivating the mutant SOD1 gene in oligodendrocyte precuror cells of SOD1 mutant mice doubled of the lifespan of these mice.   Thus we will transplant these cells first.

      Induced Pluripotent Stem cells and ES cells from mouse are being differentiated into oligodendrocyte precursor cells in culture in collaboration with Dr. Roy Ogle’s lab at LifeNet Health.  The precursor cells will be transplanted into the spinal cord of SOD1 mutant rats.  Rats will be maintained on immunosuppressant drugs to prevent graft rejection until the disease endpoint.  Spinal cords will be examined for stem cell differentiation and survival of motor neurons.  With co-investigator Dr. Jerry Nadler of EVMS, we are also testing the efficacy of anti-inflammatory compounds which reduce signaling through the 12/15 lipoxygenase – STAT4 – IL-12 pathway, in reducing inflammation, neuronal degeneration and paralysis.

    • Contact Info:
    • 757.446.5640

    • Office Location:
    • Education & Research Building

    • Undergraduate Education:
    • B.S., Biochemistry, University of Wisconsin - Madison

    • Graduate Education:
    • Postdoctoral Education:
    • Ph.D., Biology, Johns Hopkins University

    • Medical Education:
    • Residency:
    • Fellowship
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    • Bio:
    • 1984-1999, Assistant and Associate Professor, Cellular Biology and Anatomy, Medical College of Wisconsin

      1999-2004, Associate Professor, Pathology and Anatomy, EVMS

      2004-present, Professor, Pathology and Anatomy, EVMS

      2007-present, Director, Biomedical Sciences Graduate Programs, EVMS

Selected Recent Publications:

Godfrey, E.W.  and Schwarte, R.C. The role of nitric oxide signaling in the formation of the neuromuscular junction.  J. Neurocytol. 32: 591-602, 2003.

Schwarte, R.C., and Godfrey, E.W. Nitric oxide synthase activity is required for postsynaptic differentiation of the embryonic neuromuscular junction.  Devel. Biol. 273: 276-284, 2004.

Godfrey, E.W., Longacher, M.W., Neiswender, H., Schwarte, R.C., and Browning, D.D.  Guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin signaling at the developing neuromuscular junction.  Devel. Biol., 307: 195-201, 2007.

Godfrey, E.W., and Schwarte, R.C.  Nitric oxide and cyclic GMP regulate early events in agrin signaling in skeletal muscle cells.  Experimental Cell Research 316: 1935-1945, 2010.