Email

deneen@bcm.edu

Positions

Professor and Dr. Russell J. and Marian K. Blattner Chair

Center for Stem Cells and Regenerative Medicine
Baylor College of Medicine
Houston, TX US

Professor and Dr. Russell J. and Marian K. Blattner Chair

Department of Neurosurgery
Baylor College of Medicine

Education

PhD from University Of California, Los Angeles

01/2003 - Los Angeles, CA United States

Post-Doctoral Fellowship at California Institute of Technology

01/2009 - Pasadena, California United States

Professional Interests

• Glial Development
• Astrocyte Regulation of Circuit Function
• Functional Genomics of Brain Tumors
• Reactive Astrocytes and Brain Injury

Professional Statement

My laboratory studies the molecular and cellular mechanisms that control the development, diversity, and physiological roles of glial cells in the embryonic and adult central nervous system (CNS). A primary focus of my lab has been elucidating the transcriptional mechanisms that oversee developmental gliogenesis, identifying the role of Nuclear Factor I-A (NFIA) and Sox9 during embryonic glial development. We have taken these core transcriptional paradigms of glial development and applied them to neurological disease, discovering roles for NFIA in glioma tumorigenesis and in diverse glial responses after brain injury. Leveraging our expertise in glial development, neuroscience, and cancer biology we developed several de novo, native mouse models of glioma. Combining these models, with high-throughput, in vivo functional genomics screens, we recently identified several novel oncogenic drivers of glioma that function through selective remodeling of the neuronal microenvironment towards hyperactivity and epileptic states.

Another area of interest in my laboratory is understanding the nature of astrocyte diversity in the adult brain. We developed intersectional labeling approaches that identified five molecularly and functionally distinct astrocyte subpopulations. These studies highlighted the expression of Sox9 and NFIA in mature astrocytes, leading us to examine their roles in astrocyte function in the adult brain. We developed mouse lines that enabled us to decipher the role of astrocytic-NFIA and Sox9 in the adult brain. Our studies on NFIA in mature astrocytes in the adult brain revealed that it plays a region-specific role in maintaining hippocampal circuit function and associated learning and memory. In contrast, our studies on Sox9 revealed that it is required in astrocytes to maintain olfactory bulb circuits function. These combined studies illustrate that astrocytes are endowed with brain region-specific transcriptional dependencies.

Websites

Selected Publications

• 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 Apr 12;74(1):79-94. Pubmed PMID: 22500632
• 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 Mar 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 Nov 1;20(11):1520-1528. Pubmed PMID: 28892058
• Yu K, Lin CJ, Hatcher A, Lozzi B, Kong K, Huang-Hobbs E, Cheng YT, Beechar VB, Zhu W, Zhang Y, Chen F, Mills GB, Mohila CA, Creighton CJ, Noebels JL, Scott KL, Deneen B. "PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis." Nature. 2020 Feb 6;578:166-171. Pubmed PMID: 31996845