Assistant Professor Department of Neuroscience Center for Cell and Gene Therapy

Contact Information:
deneen@bcm.edu
713-798-7897

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Education:
Ph.D., University of California Los Angeles, 2002

Research Interests:
My laboratory studies the molecular and cellular mechanisms that control the generation and differentiation of glial cells. While glia constitute roughly 90% of the central nervous system (CNS) and are associated with numerous neurological disorders and malignancies, the transcriptional mechanisms that control their development and diversity remain shrouded in mystery. Using prospective isolation of stem cell populations from different stages of embryonic spinal cord, coupled with microarray analysis, we have identified a family of transcription factors (the Nuclear Factor I family or NFI) that control the specification of glial cell identity. One line of investigation in the laboratory involves using similar methods of temporal profiling of spinal cord stem cell populations from knockout embryos to identify target genes of NFI family members that are required for the initiation of gliogenesis. Another, related line of investigation includes the identification of the mechanisms that control NFI gene induction during CNS development.

Many of the markers that are normally expressed in glial cells are also expressed in gliomas, glial based malignancies of the CNS and the most common and deadly form of adult brain cancer. Consistent with this, NFI genes are also expressed in gliomas and manipulation of NFI gene expression in established glioma cell lines impacts tumor formation. Currently we are validating and extending these studies in more contemporary, stem cell models of glioma. Lastly, given that NFI genes are expressed in gliomas and may be important for tumorigenesis, the biology surrounding their normal function during gliogenesis is therefore also implicated in glioma biology. Thus, any of the NFI target genes or mechanisms that control their induction identified in the developmental studies, may also be pertinent to glioma biology and will be examined in this context

Selected Publications:

Hochstim CJ, Deneen B, Lukaszewicz A, Zhou Q, Anderson DJ (2008) The spinal cord contains positionally distinct astrocyte subtypes whose identities are specified by a homeodomain transcriptional code. Cell 133:510-522

Deneen B, Ho R, Lukaszewicz A, Hochstim CJ, Gronostajski RM, Anderson DJ. (2006) The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord. Neuron 52:953-68.

Mukouyama YS, Deneen B, Lukaszewicz A, Novitch BG, Wichterle H, Jessell TM, Anderson DJ. (2006) Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo. Proc Natl Acad Sci USA 103:1551-6.

Deneen B, Hamidi H, Denny CT. (2003) Functional analysis of the EWS/ETS target gene uridine phosphorylase. Cancer Res. 63:4268-74.

Deneen B, Welford SM, Ho T, Hernandez F, Kurland I, Denny CT. (2003) PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Mol Cell Biol. 23:3897-908.

Deneen B, Denny CT. (2001) Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation. Oncogene 20:6731-41.

Welford SM, Hebert SP, Deneen B, Arvand A, Denny CT. (2001) DNA binding domain-independent pathways are involved in EWS/FLI1-mediated oncogenesis.
J Biol Chem. 276:41977-84.

 

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(Modified:August 15, 2006- SM)