This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term objective of this research project is to understand the role of extracellular domains of proteins in protein-protein interactions for cell signaling. The short-term objective of this project is to understand the role of domain-4 of HER2 extracellular domain in protein-protein interactions (PPI) with other epidermal growth factor receptors in signaling for cell growth. The hypothesis is that protein-protein interaction surfaces have small core regions that are hydrophobic in nature and protein-protein interactions can be modulated by small molecules that interact with core regions to modulate the signaling for cell growth. As a model system we investigate the protein-protein interaction of human epidermal growth factor receptor extracellular domains. The extracellular domain of EGFRs consists of four domains, of which domain-2 and domain-4 are known to be involved in dimerization process. The importance of domain-4 in dimerization is not understood. Hence, these proteins will serve as a good model for understanding protein-protein interactions for cell signaling. Blocking of domain-4 of HER2 protein has clinical significance and thus the results from the proposed research can be applicable as """"""""translational research."""""""" Using computational docking methods, a model was proposed for HER2-EGFR heterodimer. The disruption of protein-protein interactions between EGFR-HER2, HER2-HER3 were investigated by surface plasmon resonance studies. A small hydrophobic molecule that was targeted towards the hydropbobic core region in PPI was also studied using spectroscopic and fluorescence assasys. Results suggested that a small molecule targeted to the hydrophobic part of domain-4 of HER2 protein disrupts the PPI between EGFR-HER2 and HER2-HER3. Future studies will be carried out to understand the hydrophobic core regions of the PPI in EGFR, HER2 and HER3 using experimental and computational methods.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-7 (01))
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Louisiana State University A&M Col Baton Rouge
Schools of Veterinary Medicine
Baton Rouge
United States
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Hosain, Salman B; Khiste, Sachin K; Uddin, Mohammad B et al. (2016) Inhibition of glucosylceramide synthase eliminates the oncogenic function of p53 R273H mutant in the epithelial-mesenchymal transition and induced pluripotency of colon cancer cells. Oncotarget 7:60575-60592
Pogue, A I; Dua, P; Hill, J M et al. (2015) Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD transgenic mice. J Inorg Biochem 152:206-9
Zhang, Cheng; Rissman, Robert A; Feng, June (2015) Characterization of ATP alternations in an Alzheimer's disease transgenic mouse model. J Alzheimers Dis 44:375-8
Gu, Ying; Barzegar, Mansoureh; Chen, Xin et al. (2015) Fusarochromanone-induced reactive oxygen species results in activation of JNK cascade and cell death by inhibiting protein phosphatases 2A and 5. Oncotarget 6:42322-33
Pasluosta, Cristian F; Chiu, Alan W L (2015) Modulation of grasping force in prosthetic hands using neural network-based predictive control. Methods Mol Biol 1260:179-94
Ibrahim, Sulaimon; Chowriappa, Pradeep; Dua, Sumeet et al. (2015) Classification of diabetes maculopathy images using data-adaptive neuro-fuzzy inference classifier. Med Biol Eng Comput 53:1345-60
Babu, Sainath; Uppu, Sannihith N; Martin, Brittany et al. (2015) Unusually high levels of bisphenol A (BPA) in thermal paper cash register receipts (CRs): development and application of a robust LC-UV method to quantify BPA in CRs. Toxicol Mech Methods 25:410-6
El-Saadi, Madison Wynne; Williams-Hart, Tara; Salvatore, Brian A et al. (2015) Use of in-silico assays to characterize the ADMET profile and identify potential therapeutic targets of fusarochromanone, a novel anti-cancer agent. In Silico Pharmacol 3:6
McFerrin, Harris E; Olson, Scott D; Gutschow, Miriam V et al. (2014) Rapidly self-renewing human multipotent marrow stromal cells (hMSC) express sialyl Lewis X and actively adhere to arterial endothelium in a chick embryo model system. PLoS One 9:e105411
Mahdavian, Elahe; Marshall, Monique; Martin, Patrick M et al. (2014) Caspase-dependent signaling underlies glioblastoma cell death in response to the fungal metabolite, fusarochromanone. Int J Mol Med 34:880-5

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