Bassil Kublaoui, MD PhD

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Assistant Professor of Clinical Pediatrics
Department: Pediatrics

Contact information
Division of Endocrinology and Diabetes
The Children's Hospital of Philadelphia
34th and Civic Center Blvd, 11NW30
Philadelphia, PA 19104
Philadelphia, PA 19104
Office: 215-590-3174
Fax: (267) 426-8777
Lab: (267) 426-5789
Education:
BA (Biochemistry)
Rutgers University, 1990.
BA (Psychology)
Rutgers University, 1990.
MD (Medicine)
Boston University School of Medicine, 1997.
PhD (Biochemistry)
Boston University School of Medicine, 1997.
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Description of Research Expertise

My laboratory studies the paraventricular nucleus of the hypothalamus (PVH), and the hypothalamic regulation of feeding, energy expenditure and body weight. We are currently using various mouse lines, to examine the importance of each PVH neuron subtype in feeding, energy expenditure, and body weight regulation. We use various methods including surgical and pharmacological methods as well as in-vivo neuron-specific ablation, activation and inhibition.

PVH neurons in energy homeostasis regulation: The paraventricular nucleus of the hypothalamus (PVH) functions to integrate peripheral adiposity signals such as leptin and is important in meal termination. Its ablation results in hyperphagic obesity. The PVH harbors the cell bodies of second order neurons that receive projections from leptin responsive Pomc and Npy/Agrp neurons in the arcuate. PVH Oxytocin (OXT), corticotropin releasing hormone/factor CRH/CRF and thyrotropin releasing hormone (TRH) neurons are leptin and melanocortin responsive and project to brain regions regulating satiation and energy expenditure. We aim define the role of each of the above neuron subtypes in the PVH to examine the effect on feeding regulation, energy expenditure and body weight.

Mechanism of hyperphagia in Prader-Willi Syndrome (PWS): PWS is a genetic disorder that causes neonatal feeding difficulties and failure to thrive followed by a switch to severe hyperphagia in childhood. The pathogenesis of every aspect of feeding regulation in PWS is unknown. In fact, basic elements of our understanding of the hypothalamic regulation of feeding are missing. PWS is caused by loss of several paternally inherited genes on a small locus on chromosome 15. The mouse PWS locus contains the same genes in the same order as the human locus. Like humans, mouse models of PWS also display neonatal failure to thrive with the larger deletions leading to earlier neonatal lethality. Unlike humans, PWS mice do not develop hyperphagic obesity. Many of the genes in the PWS locus are expressed in the hypothalamus and PWS is characterized by hypothalamic dysfunction. Importantly, patients with PWS have a reduced number of oxytocin neurons in the PVH of the hypothalamus as well as low circulating levels of oxytocin. We aim to define the role of the PVH and oxytocin in feeding regulation in PWS.

Selected Publications

Lai M, Roizen J, Kublaoui B: Exenetide (Byetta) Prevents Obesity in Mouse Model of Hypothalamic Obesity. Pediatric Academic Society and Pediatric Endocrine Society Annual Meeting, Vancouver, BC May 2014.

Iaumi K, Housam R, Kapadia C, Stallings VA, Medne L, Shaikh TH, Kublaoui BM, Zackai EH, Grimberg A: Endocrine phenotype of 6q16.1-q21 deletion involving SIM1 and Prader-Willi syndrome-like features. Am J Med Genet A 161A(12): 3137-43, Dec 2013.

Xi D, Roizen J, Lai M, Gandhi N, Kublaoui B: Paraventricular nucleus Sim1 neuron ablation mediated obesity is resistant to high fat diet. PLoS One 8(11): e81087, Nov 19 2013.

Kublaoui BM, Levine MA: Receptor Transduction of Hormone Action. Sperling Pediatric Endocrinology. 4th edition. Mark Sperling (eds.). Elsevier, 2013.

Xi, D, Gandhi, N. Lai, M., Kublaoui BM. : Ablation of Sim1 Neurons Causes Hyperphagia, Reduced Energy Expenditure and Obesity. Pediatric Academic Societies Annual Meeting Boston 2012.

Xi, D, Gandhi, N. Lai, M., Kublaoui BM. : Ablation of Sim1 Neurons Causes Hyperphagia, Reduced Energy Expenditure and Obesity. Pediatric Endocrine Society Annual Meeting Philadelphia 2012.

Xi Dong, Gandhi Nilay, Lai Meizan, Kublaoui Bassil M: Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. PloS one 7(4): e36453, 2012.

Xi, D, Gandhi, N. Lai, M., Kublaoui BM. : Hyperphagic obesity, reduced energy expenditure, disrupted MC4R signaling, and abnormal response to high fat diet after ablation of PVH Sim1 neurons. Society for Neuroscience annual meeting 2012.

Tolson Kristen P, Gemelli Terry, Gautron Laurent, Elmquist Joel K, Zinn Andrew R, Kublaoui Bassil M: Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression. The Journal of neuroscience : the official journal of the Society for Neuroscience 30(10): 3803-12, Mar 2010.

Shah Shuchi, Kublaoui Bassil M, Oden Jon D, White Perrin C: Screening for type 2 diabetes in obese youth. Pediatrics 124(2): 573-9, Aug 2009.

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Last updated: 07/18/2014
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