PhD, UT Southwestern Medical Center, 2007
Child Health Institute of New Jersey
Tel: (732) 235-8074
Energy homeostasis is tightly regulated by the central nervous system which controls food intake and energy expenditure and the hypothalamus is the key neural circuit for energy homeostasis. Dysfunctions in hypothalamic circuitry result in obesity/anorexia and impairment of cognitive function. Information flow within neural circuitry relies on synaptic transmission, i.e. calcium-mediated synaptic vesicle release. The long-term goal of my laboratory is to understand the neural circuitry that controls feeding and obesity in the human brain. The hypothalamus is enriched with neuropeptides but has a complicated synaptic wiring pattern. To understand the cell type- and pathway-specific regulations of synaptic transmission by hormones controlling obesity and feeding such as leptin, synaptic outputs (axonal projections) from hypothalamus will be identified using neural tracers including fluorescent beads or viral-mediated expression of fluorescent proteins; synaptic inputs to hypothalamus will be identified using optogenetic manipulations. High-resolution electrophysiological and optical methods will be used for the readout of calcium triggered synaptic vesicle release. Molecular perturbations including mouse genetics will be utilized to manipulate specific proteins involved in synaptic functions, neuropeptide release and regulations. Research areas in my lab are to investigate several fundamental questions including: 1) how peptidergic hormones including leptin, ghrelin and insulin, and neuropeptides including neuropeptide Y and proopiomelanocortin regulate synaptic functions with defined synaptic connections within the hypothalamic region in control and obese states, and to evaluate the behavioral outcomes in animals; 2) to unravel the molecular mechanisms of peptidergic regulation of synaptic functions in the hypothalamus; 3) to elucidate the molecular mechanisms of neuropeptide release in hypothalamic neurons regulated by peptidergic hormones; and finally 4) to establish a cellular-based model using derived human neurons from pluripotent stem cells or fibroblasts for study of hormonal regulation on synaptic functions in human brain.
Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Südhof TC, Wernig M. Transcription factor-mediated induction of neurons from somatic and pluripotent human cells. Nature, 2011, 476(7359):220-223
Pang ZP, Bacaj T, Yang XF, Zhou P, Südhof TC. Doc2 supports spontaneous synaptic transmission by a Ca2+-independent mechanism. Neuron, 2011, 70:244-51.
Pang ZP, Xu W, Cao P and Südhof TC. Calmodulin suppresses synaptotagmin-2 transcription in cortical neurons. Journal of Biological Chemistry, 2010, 285: 33930-33939.
Pang ZP, Cao P, Xu W and Südhof TC. Calmodulin controls synaptic strength via presynaptic activation of CaM Kinase II. Journal of Neuroscience, 2010, 30:4132-4142.
Pang ZP, Südhof TC. Cell biology of Ca2+-triggered exocytosis. Current Opinion in Cell Biology, 2010 22:496-505.
Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined transcription factors. Nature, 2010, 463:1035-1041.
Xu J, Pang ZP, Shin O-H and Südhof TC. Synaptotagmin-1 functions as Ca2+-sensor for spontaneous synaptic miniature release. Nature Neuroscience, 2009, 12:759-766.
Sun J, Pang ZP, Qin D, Fahim AT, Adachi R, Südhof TC. A dual-Ca2+-sensor model for the neurotransmitter release in a central synapse. Nature, 2007, 450:676-682.
Wu H, Xu J, Pang ZP, Ge W, Kim KJ, Blanchi B, Chen C, Südhof TC, Sun YE. Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embryonic stem cell lines. Proceedings of the National Academy of Sciences of the USA, 2007, 104:13821-13826.
Pang ZP, Shin OK, Meyer A, Rosenmund C, Südhof TC. A gain-of-function mutation in synaptotagmin-1 reveals a critical role of Ca2+-dependent SNARE-complex binding in synaptic exocytosis. Journal of Neuroscience, 2006, 26:12556-12565.
Pang ZP, Melicoff E, Padgett D, Liu Y, Teich A, Dickey B, Lin W, Adachi R, Südhof TC. Synaptotagmin-2 is essential for survival and contributes to Ca2+-triggering of neurotransmitter release in central and neuromuscular synapses. Journal of Neuroscience, 2006, 26:13493-13504.
Pang ZP, Sun J, Rizo J, Maximov A, Südhof TC. Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release. EMBO Journal, 2006, 25:2039-2050.