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Dave Poulsen
Research Associate Professor

Phone: (406) 243-4709

Email: david.poulsen@umontana.edu

After completing a Bachelors degree in Microbiology at Brigham Young University, David Poulsen obtained his Masters and Ph.D. degrees in Molecular Virology from the University of Delaware. Following the completion of his doctoral degree, Dr. Poulsen trained at the National Institutes of Health as an Intramural Training Research Award (ITRA) fellow with Dr. Bruce Cheesbro in the Laboratory of Persistent Viral Diseases (National Institute of Allergy and Infectious Disease, Rocky Mountain Laboratories). Following his training at the NIH, Dr. Poulsen served a second post-doctoral fellowship in the CNS Gene Therapy Center at Thomas Jefferson University in Philadelphia, PA. In 2001, Dr. Poulsen joined the Montana Neuroscience Institute as a Research Assistant Professor in the Department of Biomedical and Pharmaceutical Sciences at The University of Montana and as a Translational Research Scientist with St. Patrick Hospital and Health Sciences Center.

RESEARCH STATEMENT

Research in our laboratory is ultimately directed toward the development of gene therapy based applications for the treatment of neurological disorders such as epilepsy, Amyotrophic Lateral Sclerosis (ALS), chronic pain, as well as spinal cord injury and regeneration. In addition, the Poulsen laboratory is also developing genetic therapies for the treatment of hearing loss through the regeneration of hair cells within the inner ear. The primary gene delivery vehicle used in the development of these treatment strategies is the Adeno-Associated Virus (AAV). AAV is attractive as a gene delivery vector for a number of reasons. It can infect multiple cell types including terminally differentiated neurons. Most importantly, AAV is nonpathogenic and although about 85% of the world population is infected with AAV by 10 years of age, it has never been associated with pathology or disease. In fact, AAV has been used in a number of pre-clinical trials and does not appear to alter the morphology or function of transduced cells. Experimental approaches used in the development of gene therapy applications in the Poulsen laboratory range from standard molecular cloning and gene expression to the stereotactic delivery of recombinant AAV to the brain and spinal cord. Some of the specific questions we are trying to answer in the development of gene therapy based treatments include:

  1. Which of the 5 AAV serotypes are best suited for transduction of selected cell populations?

  2. Can neuroprotection from glutamate excitotoxicity be established by manipulating the expression of the neuronal and astrocytic glutamate transporters at the molecular level?

  3. Can neuronal regeneration following spinal cord injury be promoted by manipulating the RAC secondary messenger system at the molecular level?
KEY PUBLICATIONS

Poulsen D.J., Standing D., Bullshields K., Spencer K., Mecvych P.E., Babcock A.M. Overexpression of hippocampal Ca(2+)/calmodulin-dependent protein kinase II improves spatial memory. J. Neuroscience Res. Dec. 14, 2006; Epub ahead of print.

Esslinger C.S., Agarwal S., Gerdes J., Wilson P.A., Davis E.S., Awes A.N., O'Brien E., Mavencamp T., Koch H.P., Poulsen D.J., Rhoderick J.F., Chamberlin A.R., Kavanaugh M.P., Bridges R.J. (2005) The substituted aspartate analogue l-beta-threo-benzyl-aspartate preferentially inhibits the neuronal excitatory amino acid transporter EAAT3. Neuropharmacology. Nov;49(6):850-61.

Selkirk J., Steifel T., Stone I.M., Naeve G., Foster A.C., and Poulsen D.J. (2005) Over-expression of the EAAT2 glutamate transporter within neurons of mouse organotypic slice cultures leads to increased vulnerability of CA1 pyramidal cells. Eur J Neurosci. 2005 Apr;21(8):2291-6.

Stone I.M., Lurie D.I., Kelley M.W., and Poulsen D.J. (2005). Adeno-associated virus mediated gene transfer to hair cells and support cells of the murine cochlea. Molecular Therapy. 11(6):843-848.

Babcock A.M., Standing D., Bullshields K., Schwartz E., Paden C.M., Poulsen D.J.. (2005) In Vivo Inhibition of Hippocampal Ca2+/Calmodulin-dependent Protein Kinase II by RNA Interference. Mol Ther. 2005 Jun;11(6):899-905.

Harrop J.S., Poulsen D.J., Xiao W., Freese A., During M.J. (2004). Effect of altering titer, serotype, and promoter in recombinant adeno-associated virus gene therapy expression of spinal cord neurons and astrocytes. Spine. 2004 Dec 15;29(24):2787-92.

Poulsen D.J., Harrop J.S., and During M.J. (2001). Gene therapy for spinal cord injury and disease. J of Spinal Cord Med. 25(1): 2-11.

During M.J., Symes C.W., Lawlor P.A., Lin J., Dunning J., Fitzsimons H.L., Poulsen D., Leone P., Xu R., Dicker B.L., Lipski J., and Young D. (2000) An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science. 287:1453-1460.

Poulsen D.J., Favara C., Snyder E., Portis J., Chesebro B.  (1999) Increased neurovirulence of polytropic mouse retroviruses delivered by inoculation of brain with infected neural stem cells, Virology. 263, 23-29.

Poulsen D.J., Robertson S,J., Favara C.A., Portis J.L., Chesebro B.W. (1998) Mapping of a neurovirulence determinant within the envelope protein of a polytropic murine retovirus: induction of CNS disease by low levels of virus, Virology. 248, 199-207.

Poulsen D.J., Keeler Jr. C.L. (1997) Characterization of the assembly and processing of infectious laryngotracheitis virus glycoprotein B. J Gen. Virology.78, 2945-2951.

Poulsen D.J., Burton C.R.A., O’Brian J.J., Rabin S.J., Keeler Jr. C.L. (1991) Identification of the infectious laryngotracheitis virusglycoprotein gB gene by the polymerase chain reaction. Virus Genes. 5,335-347.