Laboratory of Innovative Factor-based Therapies

Theo Hagg headshot                                                                 TheRunner animated gifo Hagg 

 

TROPHIC MECHANISMS, ADULT CNS NEUROGENESIS AND CNS REPAIR

The Hagg lab investigates how novel neurotrophic mechanisms and endogenous stem cells might be used to develop CNS repair strategies.  We are currently investigating how small molecules that activate neuroprotective mechanisms might be used to reduce axon and myelin loss after a contusive spinal cord injury.  We currently investigate how vascular mechanisms could be utilized to reduce degeneration after such injuries.  Lastly, we are identifying molecular regulators of endogenous neural precursors in adult rodents which can be targeted for enhancing neurogenesis and redirect neuroblast migration towards stroke injuries.  The long term goal of these studies is to provide information that would lead to better treatment strategies for a variety of human neurological disorders, including spinal cord injury. Techniques used routinely include various refined microsurgical procedures in the brain and spinal cord of adult rats and mice, regular and confocal immunohistochemistry, Western blotting and real-time PCR.  We are members of the world-class Kentucky Spinal Cord Injury Research Center.

SELECTED RECENT PUBLICATIONS:

Journal of Neuroscience cover photoHan S, Arnold SA, Sithu SD, Mahoney ET, Geralds JT, Phuong V, Benton RL, Maddie MA, D’Sousa SE, Whittemore SR, Hagg T (2010) Rescuing vasculature with intravenous angiopoietin-1 and avb3 integrin peptide is protective after spinal cord injury. Brain 133: 1026-1042

Hagg T. (2009) From neurotransmitters to neurotrophic factors to neurogenesis. The Neuroscientist. 15:20-7.

Mahoney ET, Benton RL, Maddie MA, Whittemore SR, Hagg T. (2009) ADAM8 is selectively up-regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice. J Comp Neurol. 512:243-55 (3+ MEG).

Nakashima S., Arnold S.A., Mahoney E.T., Sithu S.D., Zhang Y.P., D'Souza S.E., Shields C.B., Hagg T. (2008) Small molecule protein tyrosine phosphatase inhibition as a neuroprotective treatment following spinal cord injury in adult rats.  Journal of Neuroscience 28: 7293-7303.

Yang P., Arnold S.A., Habas A. Hetman M., Hagg T. (2008) Ciliary neurotrophic factor mediates dopamine D2 receptor-induced neurogenesis in the adult mouse brain. Journal of Neuroscience 28: 2231-2241.

Yang P., Dankowski A., Hagg T. (2007) Protein tyrosine phosphatase inhibition reduces degeneration of dopaminergic substantia nigra neurons and projections in 6-OHDA treated adult rats.  European Journal of Neuroscience 25: 1332-1340 (1+ MEG)

Baker K.A., Hagg T. (2007) Developmental and injury-induced expression of a1b1 and a6b1 integrin in the rat spinal cord.  Brain Research 1130: 54-66 (3+ MEG)

Baker K.A., Nakashima S., Hagg T. (2007) Dorsal column sensory axons lack TrkC and are not rescued by local neurotrophin-3 infusions folllowing spinal cord contusion in adult rats.  Experimental Neurology 205: 82-91 

Yang P., Baker K.A., Hagg T. (2006) The ADAMs family: coordinators of neurvous system development, plasticity and repair.  Progress in Neurobiology 79: 73-94

Hagg T., Oudega M. (2006) Degenerative and spontaneous regenerative processes following spinal cord injury.  Journal of Neurotrauma 23: 263-280.

Hagg T. (2006) Collateral sprouting as a target for improved function after spinal cord injury.  Journal of Neurotrauma 23: 281-294.

Hagg T. (2005) Molecular regulation of adult CNS neurogenesis: an integrated view. Trends in Neurosciences 28:589-595.

Yang P., Baker K.A., Hagg T. (2005) A disintegrin and metalloprotease 21 (ADAM21) is associated with neurogenesis and axonal growth in developing and adult CNS. Journal of Comparative Neurology 490: 163-179 (2+ MEG)

antibody stained OligodendrocytesPEOPLE :

     Rollie Reid, Senior Technician

     Hillary Conway, Technician

     Erin Welsch, Technician

     Seong Kang, Postdoctoral Fellow "Adult CNS neurogenesis, CNTF regulation and stroke"

     Mattt Keasy, Postdoctoral Fellow "miRNA roles in CNTF regulation and neurogenesis"

     Jahongir Muradov, Postdoctoral Fellow "Neuroprotective treatments for spinal cord injury"

     Jun Tang, Postdoctoral Fellow "Tyrosine phosphatases as drug targets for spinal cord injury"

     Justin Geralds, MD/PhD Grad Student "Treatments for SCI and stroke"

     Sheila Arnold, PhD Grad Student, "CNTF and ADAM21 functions in neurogenesis and sprouting in the CNS"

     Vicky Tran, Biomedical Engineering Co-op student

     Dhruv Subramanian, PhD Rotation student.

 

 RECENT ALUMNI:
    Sarah Baker (PhD student), now VP Clinical Trials, NewLab Life Sciences, Canada
    Adam Baker
(PhD student), now Director Scientific Affairs, NewLab Life Sciences, Canada
    Jason Emsley (PhD student), now Medical Student at Harvard University
    Mike Lynch (summer student),
Medical Student at Univ Louisville
    Shojiro Nakashima (Postdoc), now physician in Nagao, Japan
    Peng Yang (Postdoc), now Senior Scientist at Agensys, Santa Monica

    Ed Mahoney (Postdoc), now at Eli Lilly
    Shu Han (Postdoc), now Assistant Professor in China

  

Adam21 protein 3d image

            Lab pictures :
              Party Time 
              The dangers of learning Molecular Biology
              We DO get results
              BMSing

               


SUPPORT :

 National Institutes of Health
 Kentucky Spinal and Head Injury Research Trust

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AD21 staining in cellsLouisville Skyline

 


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