The research in our laboratory focuses on understanding the molecular mechanisms that regulate neural stem cells and neurodevelopment with the goal of applying this knowledge in the treatment of neurological disorders and injuries
Stem cells have two fundamental properties: self-renewal and multipotency. During development, stem cells and resulting progenitor cells are responsible for generating all the tissues and cells of an organism. In the adult, stem cells exist in many tissues throughout life and may play critical roles in physiological functions and tissue regeneration. The maintenance of their “stemness” state and commitment to differentiation are tightly controlled by both intrinsic genetic and epigenetic programs and extrinsic stimuli.
Neural stem cells in the postnatal brain have significant roles in both normal brain functions, such as and learning, memory and the brain’s response to injuries. We are investigating the mechanisms governing the behaviors and functions of neural stem cells in both healthy conditions and in neurological diseases.
Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and noncoding RNAs have profound regulatory roles in controlling mammalian gene expression. Disturbance of these interacting systems can lead to inappropriate expression or silencing of genes, causing an array of multi-system disorders. A main focus of our research is to understand the epigenetic basis of cell fate specification and neurodevelopment.
Neurodevelopmental disorders are highly heterogeneous constellation of disorders, both in terms of etiology and clinical manifestations. Using neural stem cells as model systems, we are investigating the molecular mechanisms that regulate postnatal neuronal development during postnatal period and their implications in human neurodevelopmental disorders such as Rett Syndrome, Autism, and Fragile X syndrome.
- Guo W, Polich ED, Juan Su, J, Gao Y, Christopher, DM, Allan AM, Wang M, Wang F, Wang G, Zhao X. “Fragile X Proteins FMRP and FXR2P control synaptic GluA1 expression and neuronal maturation via distinct mechanisms,” Cell Reports, 2015. NIHMS690530, Publ.ID: CELREP1788
- Gao Y, Su J, Guo W, Polich ED, Magyar DP, Xing Y, Li H, Smrt RD, Chang Q, Zhao X. “Inhibition of miR-15a Promotes BDNF Expression and Rescues Dendritic Maturation Deficits in MeCP2-Deficient Neurons,” Stem Cells, 2015 May; 33(5):1618-29. PMID: 25639236; PMCID: PMC4409556
- Guo W, Zhang L , Christopher DM, Teng Z, Fausett SR, Klingensmith K, Jin P, and Zhao X. “RNA-binding Protein FXR2 Regulates Proliferation and Differentiation of Adult Hippocampal Neural Stem Cells by Reducing Noggin Expression,” Neuron, 2011. 70 (5):924-938
- Guo W, Allan AM, Zong R, Zhang L, Johnson EB, Schaller EG, Murthy A, Goggin SL, Eisch AJ, Oostra BA, Nelson DL, Jin P, and Zhao X. “Selective deletion of FMRP in adult neural stem cells disrupts hippocampal neurogenesis and learning,” Nature Medicine, 2011. 17(5):559-65. PMID: 21516088. (Cover story. Featured by Faculty1000 as top 2% of published articles in biology and medicine.).
- Smrt RD, Pfeiffer RL, and Zhao X. “Age-Dependent Expression of Mecp2 in a Novel Heterozygous Mosaic Mouse Model,” Hum. Mol. Genet., 2011. PMID: 21330301
- Smrt RD, Szulwach KE Pfeiffer RL, Li X, Guo W, Pathania M, Teng Z, Luo Y, Peng J, Wilson MC, Bordey A, Jin P and Zhao X. “MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase Mind Bomb-1,” Stem Cells, 2010. 28(6):1060-70. PMID: 20506192.
- Liu C, Teng Z, Santistevan NJ, Szulwach KE, Guo W, Jin P, and Zhao X. “Epigenetic regulation of miR-184 by Mbd1 governs neural stem cell proliferation and differentiation,” Cell Stem Cell, 2010. 6(5):433-44. PMID: 20452318.