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IMBS

Houston, Texas

CMB research is conducted at Baylor College of Medicine in the Texas Medical Center, Houston.
Integrative Molecular and Biomedical Sciences Graduate Program
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Benjamin Deneen, Ph.D.

Benjamin Deneen, Ph.D.

Assistant Professor, Department of Neuroscience
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 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.

Fig.1 Embryonic Glia. E18.5 mouse embryonic spinal cord section immunostained with antibodies against glial markers GFAP (red), Olig2 (green), and NFIA (blue).

Fig.2 Ectopic Astrocytes. Ectopic overexpression of NFIA in spinal cord progenitor culture promotes astrocyte differentiation. These cultures were immunostained with GFAP (red) and HA (green) to detect ectopic NFIA expression.

Fig.3 Glioma Formation. High resolution MRI image of an intracranial tumor caused by the implantation of a genetically modified glioma cell line. The yellow arrow denotes the tumor.

Selected Publications:

Kang P, Lee HK, Glasgow S, Finley M, Donti T, Gaber ZB, Graham BH, Foster AE, Novitch BG, Gronostajski RM, and Deneen B (2012) Sox9 and NFIA coordinate a transcriptional regulatory cascade during the initiation of gliogenesis. Neuron 74(1):79-94

Lee HK and Deneen B (2012) Daam2 is required for dorsal patterning via modulation of canonical Wnt signaling in the developing spinal cord. Developmental Cell 22(1):183-196.

Fancy SF, Glasgow S, Finley M, Rowitch DH, and Deneen B (2012) Evidence that NFIA inhibits repair after white matter injury. Annals of Neurology, in press.

Song H-R, Gonzalez-Gomez I, Suh GS, Commins DL, Sposto R, Ji L, Gilles FH, Deneen B* and Erdreich-Epstein A* (2010) Nuclear Factor I A is expressed in astrocytomas and is associated with improved progression-free survival. Neuro-Oncology 12(2):122-32. *Equal Contribution

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

For more publications, see listing on PubMed.

Contact Information:

Department of Neuroscience
Baylor College of Medicine
One Baylor Plaza, BCM 505
Houston, TX 77030

Phone: 713-798-7897
E-mail: deneen@bcm.edu


Updated: 7/12

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