Zhiping Pang, PhD

Zhiping Pang is a professor at the Department of Neuroscience and Cell Biology. For more information about the Pang lab, visit its dedicated website. Learn more details about graduate programs in the department.

His laboratory studies the neural basis of the regulation of feeding, satiety, metabolism, and obesity. His studies may provide insights into the neural causes and consequences of childhood obesity. He has also developed novel techniques for deriving neuronal cells from primary skin cells and pluripotent stem cells, providing novel opportunities to study the pathogenesis of neurological disorders, including pediatric developmental disorders and autism spectrum disorders.

Energy homeostasis is tightly regulated by the central nervous system, which controls food intake and energy expenditure. 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 their 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 the hypothalamus will be identified using neural tracers including fluorescent beads or viral-mediated expression of fluorescent proteins; synaptic inputs to the 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 their 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 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
4. To establish a cellular-based model using derived human neurons from pluripotent stem cells or fibroblasts for the study of hormonal regulation on synaptic functions in the human brain.

Current funding: NIAAA and NIMH

Education

• PhD, UT Southwestern Medical Center, 2007
• Postdoc, Univ and year: Stanford University, 2011

1. Scanati MS, Boreland AJ, Joel M, Hat RP, Pang ZP. Differential sensitivity of human neurons carrying μ opioid receptor (MOR) N40D variants in response to ethanol. Alcohol. 2020 Sep;87:97-109. doi: 10.1016/j.alcohol.2020.05.004. Epub 2020 Jun 17.
2. Halikere A, Popova D, Scarnati M, Hamod A, Swerdel MR, Moores JC, Tischfield JA, Hart RP, and Pang ZP. Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons. Mol Psychiatry 2019 doi: 10.1038/s41380-019-0507-0
3. Popova D, Desai N, Blendy J, Pang ZP. Synaptic regulation by OPRM1 variants in reward neurocircuitry. J Neurosci. 2019 May 20. pii: 2317-18. doi: 10.1523/JNEUROSCI.2317-18.2019. PMID: 31109961
4. Liu JJ, Mirabella VR, Pang ZP. Cell type- and pathway-specific synaptic regulation of orexin neurocircuitry. Brain Res. 2018 Oct 5. pii: S0006-8993(18)30507-9. doi: 10.1016/j.brainres.2018.10.003.
5. McGowan H, Mirabella V, Hamod A, Karakhanyan A, Mlynark N, Moore JC, Tischfield JA, Hart RP and Pang ZP. hsa-let-7c miRNA regulates synaptic and neuronal function in human neurons, Front Synaptic Neurosci.2018,10:19.doi:10.3389/fnsyn.2018.00019
6. Fantuzzo J, Mirabella V, Hamod A, Hart RP, Zahn J, Pang ZP. Intellicount: Highthroughput quantification of synaptic protein puncta by machine learning, eNeuro, 2017, 4(6). pii: ENEURO.0219-17.2017. doi: 10.1523/ENEURO.0219-17.2017.
7. Liu J, Conde K, Zhang P, Lilascharoen V, Lim BK, Seeley R, Zhu JJ, Scott MM, Pang ZP. Enhanced AMPA receptor trafficking mediates the anorexigenic effect of endogenous glucagon like peptide-1 in the paraventricular hypothalamus, Neuron, 2017, 96(4):897-909. (preview highlighted by: Lefort S, Tschöp MH, García-Cáceres C. A Synaptic Basis for GLP-1 Action in the Brain, Neuron, 2017, 96 (4): 713-715)
8. Fantuzzo JA, De Filippis L, McGowan H, Yang N, Ng YH, Halikere A, Liu JJ, Hart RP, Wernig M, Zahn JD, Pang ZP. Neurocircuitry: establishing in vitro models of neurocircuits with human neurons, Technology 2017; 5(2):87-95 Doi: 10.1142/S2339547817500054
9. DeFilippis L, Halikere A, McGowan H, Moore, JC, Tischfield JA, Hart RP, Pang ZP. Ehtanol-mediated activation of the NLRP3 inflammasome in iPS cells and iPS cellsderived neuronal progenitor cells. Mol Brain, 2016; 9(1):51. doi: 10.1186/s13041-016-0221-7.
10. Wang XF, Xia J, Liu JJ, Liu J, Mirabella, V, Pang ZP. Endogenous Glucagon-like peptide-1 suppresses high-fat food intake by reducing synaptic drive onto mesolimbic dopamine neurons. Cell Reports, 2015, doi:10.1016/j.celrep.2015.06.062