Xiaojia (Sasha) Guo, PhD
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Research Summary
We are interested in the control of vascular remodeling. Endothelial and smooth muscle cell-derived neuropilin-like protein (ESDN) is up-regulated in the neointima of remodeling arteries and modulates vascular smooth muscle cell (VSMC) growth. Receptor tyrosine kinases (RTKs) constitute a family of cell-surface receptors, including PDGFR, EGFR, VEGFR, and FGFR, controlling a variety of cellular processes, such as proliferation, differentiation, migration, and survival. RTKs are activated by binding of extracellular ligands, resulting in increased tyrosine kinase activity and phosphorylation of target proteins. Once activated, RTKs are ubiquitinated, internalized and targeted for degradation to the lysosomal compartment or locally destroyed in proteasomes. Many of these processes are regulated by ubiquitination, a post-traslational modifi cation where the small protein ubiquitin is covalently attached to a target protein by ubiquitin ligases such as c-Cbl. While polyubiquitination marks proteins for proteasomal degradation, mono- or multi-ubiquitination is sufficient to direct endocytosis and lysosomal degradation of membrane receptors.
Specialized Terms: vascular remodeling, receptor tyrosine kinases (RTKs)
Extensive Research Description
Continued detailed analyses of the involvement of ESDN in the regulation of RTK-driven pathologies is thus predicted to pave the way for therapeutic strategy for vascular diseases and other diseases involving RTK-driven tissue remodeling.
Coauthors
Research Interests
Nephrology; Vascular Remodeling
Selected Publications
- Endothelial and smooth muscle-derived neuropilin-like protein regulates platelet-derived growth factor signaling in human vascular smooth muscle cells by modulating receptor ubiquitination.Guo X, Nie L, Esmailzadeh L, Zhang J, Bender JR, Sadeghi MM. Endothelial and smooth muscle-derived neuropilin-like protein regulates platelet-derived growth factor signaling in human vascular smooth muscle cells by modulating receptor ubiquitination. The Journal Of Biological Chemistry 2009, 284: 29376-82. PMID: 19696027, PMCID: PMC2785569, DOI: 10.1074/jbc.M109.049684.
- ESDN is a marker of vascular remodeling and regulator of cell proliferation in graft arteriosclerosis.Sadeghi MM, Esmailzadeh L, Zhang J, Guo X, Asadi A, Krassilnikova S, Fassaei HR, Luo G, Al-Lamki RS, Takahashi T, Tellides G, Bender JR, Rodriguez ER. ESDN is a marker of vascular remodeling and regulator of cell proliferation in graft arteriosclerosis. American Journal Of Transplantation : Official Journal Of The American Society Of Transplantation And The American Society Of Transplant Surgeons 2007, 7: 2098-105. PMID: 17697260, DOI: 10.1111/j.1600-6143.2007.01919.x.
- Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival.Guo X, Schmitz JC, Kenney BC, Uchio EM, Kulkarni S, Cha CH. Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival. Cancer Science 2012, 103: 1474-80. PMID: 22625651, PMCID: PMC7659195, DOI: 10.1111/j.1349-7006.2012.02341.x.
- Automated quantitative analysis of tissue microarray of 443 patients with colorectal adenocarcinoma: low expression of Bcl-2 predicts poor survival.Nicholson AD, Guo X, Sullivan CA, Cha CH. Automated quantitative analysis of tissue microarray of 443 patients with colorectal adenocarcinoma: low expression of Bcl-2 predicts poor survival. Journal Of The American College Of Surgeons 2014, 219: 977-87. PMID: 25127509, DOI: 10.1016/j.jamcollsurg.2014.07.007.
- The novel tumor angiogenic factor, adrenomedullin-2, predicts survival in pancreatic adenocarcinoma.Hollander LL, Guo X, Salem RR, Cha CH. The novel tumor angiogenic factor, adrenomedullin-2, predicts survival in pancreatic adenocarcinoma. The Journal Of Surgical Research 2015, 197: 219-24. PMID: 25982376, DOI: 10.1016/j.jss.2014.11.002.
- Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis.Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Li X, Kim JD, Woolls M, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM. Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. The Journal Of Clinical Investigation 2013, 123: 5082-97. PMID: 24177422, PMCID: PMC3859420, DOI: 10.1172/JCI67752.
- Renalase: its role as a cytokine, and an update on its association with type 1 diabetes and ischemic stroke.Guo X, Wang L, Velazquez H, Safirstein R, Desir GV. Renalase: its role as a cytokine, and an update on its association with type 1 diabetes and ischemic stroke. Current Opinion In Nephrology And Hypertension 2014, 23: 513-8. PMID: 24992568, PMCID: PMC4383282, DOI: 10.1097/MNH.0000000000000044.