Emory University School of Medicine
Department of Pharmacology
5029 Rollins Research Center
1510 Clifton Road
Atlanta, GA 30322-3090Phone :
Posttranscriptional regulation in normal brain function, development and brain diseases
We are interested in how RNA-binding proteins and microRNAs govern the normal brain development and function, and how posttranscriptional dysregulation at the steps of mRNA biogenesis and translation leads to malfunction of neurons and glia, which underlies many mental and neurological diseases. Taking a multidisciplinary strategy and a combination of molecular, cellular and pharmacological approaches, our current research focuses on the following directions:
(1) Translation regulation in neuronal development, synaptic plasticity and mental disorders
Rapid and accurate regulation of protein synthesis in brain neurons, especially at the synapses, is a critical mechanism that governs neuronal network development, synaptic plasticity, and cognitive function. We have a long standing interest in the fragile X mental retardation protein (FMRP), a selective RNA-binding protein controls mRNA translation whose absence leads to fragile X syndrome (FXS), the leading cause of inherited intellectual disability. We are currently investigating various mRNA targets of FMRP to elucidate how FMRP collaborates with microRNAs to control neuronal translation in response to developmental and synaptic signals and how FMRP deficiency leads to abnormal synaptic development and plasticity.
Moreover, we have recently launched on an exciting new project to delineate regulation of translation and homeostasis of the mRNAs encoding the brain derived neurotrophic factor (BDNF), which is a key factor controlling a broad spectrum of brain function whose dysregulation causes numerous neurological and cognitive disorders. We are currently investigating how RNA-binding proteins and microRNAs control BDNF production under physiological and pathological neuronal activity changes represented by that in epilepsy.
(2) mRNA homeostasis in myelination and white matter diseases
We currently focus on the selective RNA-binding protein QKI, a key factor controlling proliferation and differentiation of myelin producing glia and myelin formation in response to developmental signals. Emerging evidence indicated the involvement of QKI function in several human diseases, including myelin repair in multiple sclerosis, white matter defects in schizophrenia, and glioma tumorigenesis. We have established state-of-the-art molecular and cellular tools and genetically engineered animal models, which allowed us to identify a sophisticated molecular cascade that controls alternative splicing, stability, localization and translation of numerous mRNA targets of QKI in normal myelinogenesis, neural protection and pathogenesis of myelin disorders. Moreover, we are taking, genetic and pharmacological approaches to manipulate QKI function to promote myelin regeneration.
Ph.D., Vanderbilt University
Postdoctoral Fellow/Research Associate, Emory University
Research Assistant Professor, Emory University, 1995-1998
Assistant Professor, Emory University, 1999-2005
Associate Professor, Emory University, 2005—Present