Scripps Florida - The Scripps Research Institute Department of Neuroscience

Department of Neuroscience

FACULTY DIRECTORY

Baoji Xu, Ph.D.

Baoji Xu

Professor

Ph.D., Stanford University, 1995

Adjunct Professor, Department of Pharmacology and Physiology, Georgetown University

Department of Neuroscience
130 Scripps Way 3C1
Jupiter, Florida 33458
Telephone: 561-228-2340
Fax: 561-228-2341

Email: bxu@scripps.edu
Website: http://www.scripps.edu/xu/

Research Interests

We are interested in understanding how neural circuits are formed, modified, and maintained in the brain. Brain neural circuits are the structural basis for human behaviors. Abnormalities or degenerative changes in neural circuits have been shown to cause many disorders, including autism, mental retardation, depression, Alzheimer’s disease, and obesity. We use brain-derived neurotrophic factor (BDNF) as a model molecule to study how growth factors regulate the development and function of neural circuits. Our research employs a combination of mouse genetic, biochemical, molecular, histological, and behavioral approaches. There are three main ongoing research projects in the laboratory.

Local protein synthesis and dendritic spine plasticity: Hundreds of mRNA species are transported to dendrites, and their local translation in dendrites has been shown to be essential for lasting synaptic plasticity, which is believed to be the cellular basis of learning and memory. Our results indicate that local protein synthesis in dendrites also controls refinement of neuronal connections during development. Dendritic spines are the postsynaptic sites for the vast majority of excitatory synapses. We found that BDNF synthesized in dendrites was essential for elimination of excess dendritic spines and enlargement of the remaining spines in the brain. We are investigating the molecular mechanisms that control dendritic localization of mRNA and translation of dendritic mRNA. To this end, we have special interests in RNA-binding proteins, including fragile X mental retardation protein (FMRP), whose absence causes mental retardation and autism. We also search for molecular pathways through which dendritically synthesized BDNF regulates growth and elimination of dendritic spines.

Control of appetite and body weight: Obesity results from excess food intake and/or reduced energy expenditure. We and others have shown that BDNF is an important regulator of body weight. Mutations in the genes for BDNF and its receptor TrkB cause insatiable appetite and massive obesity in humans and mice. Furthermore, several Bdnf gene variants have been linked to human obesity. Many brain regions, such as the hypothalamus and the brainstem, play crucial roles in the control of appetite and energy expenditure. We put a lot of efforts into identifying the neural circuits that mediate the effect of BDNF on appetite and energy expenditure. We hope to understand how BDNF interacts with other appetite-controlling factors (e.g. leptin and insulin) to alter the structure and activity of these neural circuits. Identification of the neural circuits and elucidation of the BDNF action on them will greatly enhance our understanding of human obesity and hopefully bring us closer to a strategy for effective drug treatments of obesity.

Neurodegenerative diseases: Many neurodegenerative diseases (e.g. Alzheimer’s disease) are characterized by the progressive loss of synapses and, subsequently, neurons themselves. Since BDNF strongly promotes synaptogenesis, synaptic transmission, and neuronal survival, it could be a potent agent for treatment of neurodegenerative diseases. In fact, several studies, including ours, have shown that transgenic or viral BDNF overexpression ameliorates Alzheimer’s disease and Huntington’s disease in animal disease models. We aim to identify small molecules that can enhance Bdnf gene expression by stimulating either transcription or translation. These small molecules should be capable of increasing TrkB activity without altering the spatial and temporal specificity of the BDNF action. They have potentials as therapeutic agents for Alzheimer’s disease, Huntington’s disease, and other brain disorders.

Selected Publications

Xu B. and Xie X. (2016) Neurotrophic factor control of satiety and body weight. Nat. Rev. Neurosci. 17: 282-292.

An JJ, Liao GY, Kinney CE, Sahibzada N and Xu B. (2015) Discrete BDNF neurons in the paraventricular hypothalamus control feeding and energy expenditure. Cell Metab. 22: 175-188.

Orefice LL, Waterhouse EG, Partridge JG, Lalchandani RR, Vicini S, and Xu B. (2013) Distinct roles for somatically and dendritically synthesized BDNF in morphogenesis of dendritic spines. J. Neurosci.33: 11618-11632.

Waterhouse EG, An JJ, Orefice LL, Baydyuk M, Liao GY, Zheng K, Lu B, and Xu B. (2012) BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission. J. Neurosci. 32: 14318-14330.

Liao GY, An JJ, Gharami K, Waterhouse EG, Vanevski F, Jones KR, and Xu B. (2012) Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin. Nat. Med. 18: 564-571 (see comments here and here).

Kaneko M, Xie Y, An JJ, Stryker, MP, and Xu B. (2012) Dendritic BDNF synthesis is required for late-phase spine maturation and recovery of cortical responses following sensory deprivation. J. Neurosci. 32: 4790-4802.

Baydyuk M, Russell T, Liao GY, An JJ, Reichardt LF and Xu B. (2011) The TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons. Proc. Natl. Acad. Sci. USA 108: 1669-1674 (see comments here).

Xie Y, Hayden MR and Xu B. (2010) BDNF overexpression in the forebrain rescues Huntington’s disease phenotypes in YAC128 mice. J. Neurosci. 30: 14708-14718.

An JJ, Gharami K, Liao GY, Woo NH, Lau AG, Vanevski F, Torre ER, Jones KR, Feng Y, Lu B, and Xu B. (2008) Distinct role of long 3′ UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell 134: 175-187.

Xu B., Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, and Reichardt LF. (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat. Neurosci. 6: 736-742 (see comments here).

Awards, Recognition, Appointments, and Honors

1989-1994 Predoctoral Fellowship award, Rockefeller Foundation
2003-2006 Whitehall Foundation Grant Award

2004-2007 American Heart Association Scientist Development Grant Award
2008-present Ad hoc reviewer of NIH Study Sections (CNNT, IPOD, MNPS, NIBIB K, NSD-B, NSD-C, and ZRG1 EMNR-B)

2012-2016 Appointed member of NIH Neurological Sciences and Disorders C (NSD-C) Study Section