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Ben Deneen

Benjamin Deneen

E-mail: deneen@bcm.edu

Assistant Professor, Baylor College of Medicine

B.S., University of California, Davis, 1997
Ph.D., University of California, Los Angeles, 2002
Postdoc, California Institute of Technology, 2003-08


Glial cell development and disease

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

Welford SM, Hebert SP, Deneen B, Arvand A, Denny CT (2001) DNA binding domain-independent pathways are involved in EWS/FLI1-mediated oncogenesis. Journal of Biological Chemistry 276:41977-41984.

Deneen B, Denny CT (2001) Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation. Oncogene 20:6731-6741.

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. Molecular and Cellular Biology 23:3897-3908.

Deneen B, Hamidi H, Denny CT (2003) Functional analysis of the EWS/ETS target gene uridine phosphorylase. Cancer Research 63:4268-4274.

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. Proceedings of the National Academy of Sciences USA 103:1551-1556.

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 52:953-968.

Hochstim C, Deneen B, Lukaszewicz A, Zhou Q, Anderson DJ (2008) Identification of positionally distinct astrocyte subtypes whose identities are specified by a homeodomain code. Cell 133:510-522.

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

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


Contact Information

Benjamin Deneen, Ph.D.
Department of Neuroscience
Center for Cell and Gene Therapy
Baylor College of Medicine
One Baylor Plaza N1120
Houston, Texas 77030, U.S.A.

Tel: (713) 798-7897
 
E-mail: deneen@bcm.edu

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