- Ctr Stem Cell & Regen
- Baylor College of Medicine
- Houston, TX, US
- Dan L Duncan Comprehensive Cancer Center
- Baylor College of Medicine
- Houston, Texas, United States
- PhD from University Of California, Los Angeles
- Post-Doctoral Fellowship at California Institute of Technology
- 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.
- Kang P, Lee HK, Glasgow SM, Finley M, Donti T, Gaber ZB, Graham BH, Foster AE, Novitch BG, Gronostajski RM, Deneen B. "Sox9 and NFIA Coordinate a Transcriptional Regulatory Cascade during the Initiation of Gliogenesis.." Neuron. 2012 April 12;74(1):79-94. Pubmed PMID: 22500632
- Glasgow S, Zhu W, Stolt CC, Huang TW, Chen F, LoTurco JJ, Neul JL, Wegner M, Mohila C, and Deneen B. "Mutual Antagonism Between Sox10 and NFIA Regulates Diversification of Glial Lineages and Glioma Sub-Types." Nature Neuroscience. 2014 October 1;17(10):1322-1329. Pubmed PMID: 25151262
- Lee HK, Chaboub LS, Zhu W, Zollinger D, Rasband MN, Fancy SP, Deneen B.. "Daam2-PIP5K Is a Regulatory Pathway for Wnt Signaling and Therapeutic Target for Remyelination in the CNS.." Neuron. 2015 March 18;85(6):1227-1243. Pubmed PMID: 25754822
- John Lin CC, Yu K, Hatcher A, Huang TW, Lee HK, Carlson J, Weston MC, Chen F, Zhang Y, Zhu W, Mohila CA, Ahmed N, Patel AJ, Arenkiel BR, Noebels JL, Creighton CJ, Deneen B.. "Identification of diverse astrocyte populations and their malignant analogs.." Nature Neuroscience. 2017 March 1;20(2):396-405. Pubmed PMID: 28166219
- Glasgow SM, Carlson JC, Zhu W, Chaboub LS, Kang P, Lee HK, Clovis YM, Lozzi BE, McEvilly RJ, Rosenfeld MG, Creighton CJ, Lee SK, Mohila CA, and Deneen B. "Glia-specific enhancers and chromatin structure regulate NFIA expression and glioma tumorigenesis." Nature Neuroscience. 2017 November 1;20(11):1520-1528. Pubmed PMID: 28892058