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Research Interests:

The focus of our research is to develop new therapies for the treatment of malignant and degenerative diseases of the central nervous system. We are currently developing "gene therapies" for the treatment of brain tumors and neurodegenerative diseases such as Hurler's syndrome.

Our group is targeting primary brain tumors such as glioblastoma and metastatic brain tumors such as breast cancer for treatment by gene therapy. We are delivering viral and/or nonviral vectors into brain tumors that exert anti-tumor effects by inhibiting angiogenesis, or by killing tumor cells directly, or by facilitating immune-mediated destruction of the tumor. The combination of these three strategies shows great promise for eliciting superior anti-tumor efficacy compared to single gene strategies because the tumor cells are attacked from multiple fronts simultaneously. Currently, we are working with three vectors in the lab to attack cancer: Adeno-associated virus-5, recombinant adenovirus, and Sleeping Beauty nonviral plasmid vectors. Our long-term plan is to optimize delivery and therapeutic efficacy in animal models (mice and dogs) then proceed to human clinical trials.

We are also interested in using gene transfer to correct neurodegenerative diseases that result from a missing enzyme (i.e. Hurler's syndrome, Canavan disease, others). Currently we are using adeno-associated virus-5 and two nonviral vectors to achieve this goal: the Sleeping Beauty transposable element and the bacteriophage f C31 integrase. Challenges of gene delivery, long-term expression of therapeutic genes, and safety are the focus of our research in this area. Only when these challenges have been overcome will clinical success be achieved using gene therapy for the treatment of neurodegenerative diseases.

Selected Publications:

Wu A, Oh S, Gharagozlou S, Vedi RN, Ericson K, Low WC, Chen W, Ohlfest JR. In vivo vaccination with tumor cell lysate plus CpG oligodeoxynucleotides eradicates murine glioblastoma. J Immunother (1997). 2007 Nov-Dec;30(8):789-97.

Candolfi M, Curtin JF, Nichols WS, Muhammad AG, King GD, Pluhar GE, McNiel EA, Ohlfest JR, Freese AB, Moore PF, Lerner J, Lowenstein PR, Castro MG. Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression. J Neurooncol. 2007 Nov;85(2):133-48. Epub 2007 Sep 15.

Oh S, Odland R, Wilson SR, Kroeger KM, Liu C, Lowenstein PR, Castro MG, Hall WA, Ohlfest JR. Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter. J Neurosurg. 2007 Sep;107(3):568-77.

Oh S, Pluhar GE, McNeil EA, Kroeger KM, Liu C, Castro MG, Lowenstein PR, Freese A, Ohlfest JR. Efficacy of nonviral gene transfer in the canine brain. J Neurosurg. 2007 Jul;107(1):136-44.

Candolfi M, Pluhar GE, Kroeger K, Puntel M, Curtin J, Barcia C, Muhammad AK, Xiong W, Liu C, Mondkar S, Kuoy W, Kang T, McNeil EA, Freese AB, Ohlfest JR, Moore P, Palmer D, Ng P, Young JD, Lowenstein PR, Castro MG. Optimization of adenoviral vector-mediated transgene expression in the canine brain in vivo, and in canine glioma cells in vitro. Neuro Oncol. 2007 Jul;9(3):245-58.

Wu A, Oh S, Ericson K, Demorest ZL, Vengco I, Gharagozlou S, Chen W, Low WC, Ohlfest JR. Transposon-based interferon gamma gene transfer overcomes limitations of episomal plasmid for immunogene therapy of glioblastoma. Cancer Gene Ther. 2007 Jun;14(6):550-60. Epub 2007 Apr 6.

Wu A, Wiesner S, Xiao J, Ericson K, Chen W, Hall WA, Low WC, Ohlfest JR. Expression of MHC I and NK ligands on human CD133+ glioma cells: possible targets of immunotherapy.
J Neurooncol. 2007 Jun;83(2):121-31. Epub 2006 Nov 1. Erratum in: J Neurooncol. 2007 Jun;83(2):133.

Candolfi M, Kroeger KM, Pluhar GE, Bergeron J, Puntel M, Curtin JF, McNiel EA, Freese AB, Ohlfest JR, Moore P, Lowenstein PR, Castro MG. Adenoviral-mediated gene transfer into the canine brain in vivo. Neurosurgery. 2007 Jan;60(1):167-77; discussion 178.

Candolfi M, Kroeger KM, Pluhar GE, Bergeron J, Puntel M, Curtin JF, McNiel EA, Freese AB, Ohlfest JR, Moore P, Lowenstein PR, Castro MG. Adenoviral-mediated gene transfer into the canine brain in vivo. Neurosurgery. 2007 Jan;60(1):167-77.

Current Graduate Students:

Stacy Decker (Neuroscience, University of Minnesota).