Benjamin Deneen, Ph.D.
Associate Professor, Center for Cell and Gene Therapy, Department of Neuroscience, Baylor College of Medicine
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.Using the induction of NFI genes at the onset of gliogenesis as a starting point, my laboratory has begun to unravel the upstream and downstream mechanisms that encompass NFI gene function during this crucial developmental interval. Another focal point of my laboratory is to translate the molecular mechanisms that control glial fate determination to neurological disease. We have found that NFI genes are also expressed in human gliomas and and human white matter injury (HIE and Multiple Sclerosis) and contributes to the associated pathology of these diseases in animal models. Therefore the goal of my research program is identify novel paradigms controlling gliogenesis and determine whether they contribute to neurological disease.
1. Lee HK, Chaboub LS, Zhu W, Zollinger D, Rasband MN, Fancy SF, and Deneen B. (2015) Daam2-PIP5K is a novel regulatory pathway for Wnt signaling and therapeutic target for remyelination in the CNS. Neuron (In Press)
2. Glasgow S, Zhu W, Stolt CC, Huang TW, Chen F, LoTurco JJ, Neul JL, Wegner M, Mohila C, and Deneen B. (2014) Mutual Antagonism Between Sox10 and NFIA Regulates Diversification of Glial Lineages and Glioma Sub-Types. Nature Neuroscience 17(10): 1322-1329. PMID:25151262
3. Garcia I, Bhullar PK, Tepe B, Ortiz-Guzman J, Huang L, Herman AM, Chaboub LS, Deneen B, Justice NJ, Arenkiel BR (2014) Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the olfactory bulb. Brain Structure Function Sep 16. [Epub ahead of print] PMID: 25224546
4. Glasgow S, Laug D, Brawley V, Zhang Z, Corder A, Yin Z , Wong STC, Li XN, Foster AE, Ahmed A, and Deneen B. (2013) The miR223-NFIA Axis Regulates Glial Precursor Proliferation and Tumorigenesis in the CNS. Journal of Neuroscience 33(33):13560-13568. PMID: 23946414
**Featured in Science “Editors Choice” http://www.sciencemag.org/content/341/6150/1044.4.short
5. Lee JS, Xiao J, Patel P, Schade J, Wang J, Deneen B, Erdreich-Epstein A, Song H-R. (2013) A novel tumor-promoting role for Nuclear Factor I A (NFIA) in glioblastomas is mediated through negative regulation of p53, p21, and PAI1. Neuro-Oncology 16(2):191-203 PMID: 24305710
6. Molofsky A, Glasgow S, Chaboub L, Tsai H-H, Murnen AT, Fancy SF, Yuen T, Mahireddy L, Baranzini S, Deneen B, Rowitch DH, Oldham M. (2013) Expression profiling of putative astrocyte precursors in the developing spinal cord identifies Sox9-Nfe2l1 interactions. Glia 61(9):1518-1532.