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Department of Neuroscience

Baoji Xu, Ph.D.

Department of Neuroscience
Florida Campus
Laboratory Website
(561) 228-2340

Scripps Research Joint Appointments

Faculty, Graduate Program

Other Joint Appointments

Adjunct Professor, Department of Pharmacology and Physiology, Georgetown University

Research Focus

The goal of our laboratory is to understand how both healthy and diseased brains work. We focus on the mechanisms by which growth factors such as brain-derived neurotrophic factor (BDNF) regulate the development and function of brain neural circuits that control body weight, learning, mood, and social behaviors. We hope that our research will lead to discovery of novel therapeutics for neurodegenerative diseases, neurodevelopmental disorders, and obesity.

Research Projects

Central control of eating behavior and obesity

Obesity has become a leading worldwide health problem because of its high prevalence. Obese children and adults are developing type-2 diabetes at high rates, and are at significant risk for life-threatening cardiovascular disease and cancer. Despite the enormous economic cost of obesity, there is currently no effective and safe treatment available for this health issue. Understanding the central mechanism that controls food intake and energy expenditure will provide opportunities to develop novel interventions for obesity.

Our group has played a leading role in discovering brain-derived neurotrophic factor (BDNF) as a key regulator of body weight by suppressing food intake and promoting energy expenditure. We and others have shown that disruption in BDNF-to-TrkB signaling leads to severe obesity in humans and mice. We are conducting studies to identify neural circuits that control appetite and energy expenditure in mice by using biochemical, behavioral, genetic, physiological and viral approaches. Identification of the circuits will allow us to further investigate what signals are generated upon eating to stimulate BDNF release from neurons in the brain, how the released BDNF alters the activity of the circuits, and how the circuits stop eating and stimulate energy utilization. This research project will help us understand not only how our body controls eating, a fundamental behavior, but also how the brain functions.

Autism spectrum disorders

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with deficits in two core domains: social interaction and communication, and repetitive behaviors or restrictive behaviors. Prevalence of ASD is 1 in 68 children under 8 years of age in the USA and is higher in males (1 in 42) than in females (1 in 189). There is a strong genetic basis for ASD. Mutations in hundreds of genetic loci, including both germline and de novo mutations, have been implicated in underlying ASD. Because of this high genetic heterogeneity, it is essential to find common pathophysiology pathways in order to develop therapeutic strategies for ASD. One common pathophysiology pathway underlying ASD is likely to be exaggerated protein synthesis, as mutations in several negative regulators of protein synthesis, such as PTEN, TSC1, TSC2 and FMRP, cause ASD. We are interested in identifying groups of cells in which exaggerated translation causes ASD-like behaviors and elucidating molecular mechanisms by which exaggerated translation alters the function of the cells. 

Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease that causes problems with memory, thinking and behavior. Recent human genomic studies have implicated dysfunction of microglial cells, the resident immune cells in the brain, as an important cause for AD. Microglial dysfunction likely leads to deficits in clearance of toxic protein aggregates such as beta-amyloid (Ab) polymers and cell debris. We are interested in the cellular and biochemical process by which microglia sense and remove cell debris and protein aggregates in the brain. In addition, aging is the largest risk factor for AD and is associated with a reduction in uptake and metabolism of glucose, the main fuel source of the brain. We are also interested in elucidating biochemical pathways that regulate glucose metabolism in the brain and investigating how the activity of these pathways is reduced in aging brain.

Drug discovery

No disease-modifying treatment is currently available for AD. In light of the failure of recent clinical trials that target Ab, there is an urgent need to develop drugs that target the AD pathophysiology, i.e. dysfunction and loss of synapses followed by neuronal loss. It is well documented that BDNF promotes neuronal survival and stimulates synaptogenesis and synaptic plasticity. Thus, increasing BDNF levels could halt or reverse the progress of AD by enhancing the function of existing synapses, inducing formation of new synapses, and preventing additional neuronal loss. The proof of principle for this concept has been shown in AD animal models. However, BDNF is a poor therapeutic agent due to its pharmacological properties. It is also difficult to find small-molecule compounds (~500 Da) that mimic the action of 56-fold larger BDNF protein (~28 kDa in dimer). We are searching for small-molecule compounds that stimulate production of endogenous BDNF in neurons. Because reduced levels of BDNF are also associated with obesity, anxiety and other brain disorders, these BDNF-boosting compounds could be useful for other diseases. 



Ph.D., Molecular Biology, Stanford University, Stanford, California
B.S., Biology, Xiamen University, Xiamen, Fujian, China

Awards & Professional Activities

Rockefeller Foundation Predoctoral Fellowship
American Heart Association Scientist Development Award
Whitehall Foundation Award
Georgetown University Annual IPN Junior Faculty Award
Ad hoc member of NIH CNNT, MNPS, ZRG1 EMNR-B, and NSD-C Study Sections
Regular member of NIH Neurological Sciences and Disorders C (NSD-C) Study Section

Ongoing Support

R01 DK089237 (PI: Xu)
Regulation of energy homeostasis by BDNF
The major goals of this project are to elucidate how BDNF controls energy homeostasis by regulating the formation of neural circuits in the hypothalamus using a unique mouse mutant that is deficient in local BDNF synthesis.

R01 DK103335 (PI: Xu)
Unraveling the role of PVH BDNF neurons in energy balance
The major goals of this project are to determine the role of BDNF-expressing neurons in the paraventricular hypothalamus in the control of food intake and energy expenditure and to elucidate the neural circuits linking these neurons.

R01 DK112759 (PI: Yang)
Astrocytic target mechanisms in obesity
The major goals of this project are to investigate the role of astrocytes in the control of food intake and energy expenditure by modulating the function of neurons in the arcuate nucleus of the hypothalamus. Role: co-investigator

R21 NS095425 (PI: Xu)
Astrocytic TrkB in diet-induced obesity
The major goals of this project are to investigate the role of the truncated TrkB receptor expressed in hypothalamic astrocytes and astrogliosis in diet-induced obesity

R21 MH108046 (PI: Xu)
Neural basis underlying autistic behaviors
The major goals of this project are to determine whether increasing protein synthesis in neurons or astrocytes leads to autistic-like behaviors in mice.


Selected References

Xu B and Xie X. (2016) Neurotrophic 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.

Baydyuk M, Xie Y, Tessarollo L, and Xu B. (2013) Midbrain-derived neurotrophins support survival of immature striatal projection neurons. J. Neurosci. 33: 3363-3369.

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.

Kang Z, An JJ, Yang F, Xu W, Xu Z, Wu J, Hökfelt T, Fisahn A, Xu B, and Lu B. (2011) TrkB signaling in parvalbumin-positive interneurons is critical for gamma-band network synchronization in hippocampus.  Proc. Natl. Acad. Sci. USA 108: 17201-17206.

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).


Department of Neuroscience

If the Splice Is Right – BDNF to Dendrites, APP to Endosomes

Brain Protein Tied to Retardation – ABC News

BBC News – Obesity gene’s role revealed in mice study

One gene mutation causes uncontrolled obesity