? Scientific Core Human induced pluripotent stem cells (iPSCs) offer a remarkable opportunity to study human tissue and organ development and to discover the molecular and cellular basis of human diseases. Capable of being differentiated into nearly any cell type in the human body, iPSCs have proven to be invaluable for studying previously inaccessible cell populations such as neural cells of the developing and mature brain. These populations are among the most relevant cell types in the study of neurotropic viruses such as Zika virus (ZIKV) and West Nile virus (WNV). ZIKV, a mosquito-borne flavivirus, is currently reported to be circulating in 26 countries and territories in Latin America and the Caribbean. While ZIKV infection has been linked to microcephaly in newborns and other brain abnormalities such as Guillain-Barr syndrome, how ZIKV impairs brain development and function is unknown. WNV, another member of flavivirus genus, can also lead to serious neurologic illnesses such as encephalitis or meningitis, with the underlying mechanism remains elusive and there is no reported studies using human cellular models. Since access to human brain tissue is very limited, generating new cellular models using human iPSCs can facilitate biological discovery and drug development. Recently developed technology to generate 3D cerebral organoids from iPSCs holds the promise of allowing for more accurate models that recapitulate key processes and features of human brain development. To model ZIKV and WNV infections of the central nervous system, the Scientific Core will optimize and standardize protocols for differentiation of disease-relevant specific cell types (Specific Aims 1 and 2), generate genetically-modified iPSC lines for functional studies (Specific Aim 1), supply cells and provide on-site training for all projects (Specific Aim 2), and perform bioinformatics analyses for transcriptomic profiling (Specific Aim 3). The Scientific Core plays an essential role in setting standards for reproducible conditions for cell culture through cross-training of personnel in Projects 2 & 3, which is a critical component of robust platform development. The Scientific Core will work closely with Project 1 on technology development and protocol optimization and the Administrative Core for documentation and dissemination of validated protocols.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI131130-02
Application #
9461006
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li (2018) A previously undetected pathology of Zika virus infection. Nat Med 24:258-259
Ho, Cheng-Ying; Castillo, Nicolas; Encinales, Liliana et al. (2018) Second-trimester Ultrasound and Neuropathologic Findings in Congenital Zika Virus Infection. Pediatr Infect Dis J 37:1290-1293
Yang, Shu; Xu, Miao; Lee, Emily M et al. (2018) Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry. Cell Discov 4:31
Lang, Jianshe; Cheng, Yichen; Rolfe, Alyssa et al. (2018) An hPSC-Derived Tissue-Resident Macrophage Model Reveals Differential Responses of Macrophages to ZIKV and DENV Infection. Stem Cell Reports 11:348-362
Song, Guang; Rho, Hee-Sool; Pan, Jianbo et al. (2018) Multiplexed Biomarker Panels Discriminate Zika and Dengue Virus Infection in Humans. Mol Cell Proteomics 17:349-356
Yoon, Ki-Jun; Vissers, Caroline; Ming, Guo-Li et al. (2018) Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence. J Cell Biol 217:1901-1914
Qian, Xuyu; Jacob, Fadi; Song, Mingxi Max et al. (2018) Generation of human brain region-specific organoids using a miniaturized spinning bioreactor. Nat Protoc 13:565-580
Ye, Fei; Kang, Eunchai; Yu, Chuan et al. (2017) DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis. Neuron 96:1041-1054.e5
Yoon, Ki-Jun; Song, Guang; Qian, Xuyu et al. (2017) Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins. Cell Stem Cell 21:349-358.e6
Wen, Zhexing; Song, Hongjun; Ming, Guo-Li (2017) How does Zika virus cause microcephaly? Genes Dev 31:849-861

Showing the most recent 10 out of 16 publications