This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human epidermal growth factor receptor 2 (HER2) is a member of the human epidermal growth factor receptor kinases (other members include EGFR or HER1, HER3, and HER4) that is involved in signaling cascades for cell growth and differentiation. It is well established that HER2-mediated heterodimerization has important implications in cancer. Deregulation of signaling pathways and overexpression of HER2 is known to occur in cancer cells. We have designed peptidomimetics that inhibit signaling for cell growth. The central hypothesis is that peptidomimetics designed based on the structure of the HER2-herceptin complex will inhibit the HER2-mediated signal for cell growth. To understand the molecular mechanism of signaling mediated by HER2 protein, a peptidomimetic HERP5 was used. Thea objectives of this study are (a) to evaluate the binding properties of HERP5 to HER2 on the cell surface;(b) to evaluate the binding of fluorescently labeled HERP5 to domain IV of HER2 protein;c) to evaluate the binding of HERP5 and its analogs with HER2 extracellular domain using structural biology techniques;and d) to model the dimerization of HER2 with other receptors using computational methods. Binding of fluorescently labeled HERP5 to HER2 protein was evaluated by fluorescence assay, microscopy, and circular dichroism spectroscopy. Results indicated that HERP5 binds to the extracellular region of the HER2 protein. A model was proposed for HER2-EGFR dimerization and possible blocking by HERP5 peptidomimetic using a protein-protein docking method. Future studies will be focused on HER2 protein expression, purification, and blocking of HER2-EGFR interactions using surface plasmon resonance technique and structural biology methods.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
2P20RR016456-09
Application #
8168133
Study Section
Special Emphasis Panel (ZRR1-RI-7 (01))
Project Start
2010-07-15
Project End
2011-04-30
Budget Start
2010-07-15
Budget End
2011-04-30
Support Year
9
Fiscal Year
2010
Total Cost
$55,546
Indirect Cost
Name
Louisiana State University A&M Col Baton Rouge
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
075050765
City
Baton Rouge
State
LA
Country
United States
Zip Code
70803
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
Gu, Ying; Chen, Xin; Shang, Chaowei et al. (2014) Fusarochromanone induces G1 cell cycle arrest and apoptosis in COS7 and HEK293 cells. PLoS One 9:e112641
Patwardhan, Gauri A; Hosain, Salman B; Liu, David X et al. (2014) Ceramide modulates pre-mRNA splicing to restore the expression of wild-type tumor suppressor p53 in deletion-mutant cancer cells. Biochim Biophys Acta 1841:1571-80

Showing the most recent 10 out of 179 publications