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 goal of the research in my laboratory is to dissect the cellular activities of NR4A nuclear receptors in the genetic model organism C. elegans. The cellular activities of NR4A, including mechanisms of transcriptional regulation and interactions with signal transduction pathways, are poorly understood. Previous studies have supported our central hypothesis that NHR-6, the NR4A ortholog in C. elegans, has distinct, dualistic functions in regulating cell proliferation and cell differentiation during organogenesis.
The aims of the current project are focused on identifying the specific pathways by which NHR-6 regulates these distinct processes. We are addressing this question through two specific aims: 1) Identify NHR-6 target genes using whole-animal chromatin immunoprecipitation (ChIP);and 2) Identify candidate signaling pathways regulating NHR-6 using genetic interaction studies. For the first aim, we have been successful in optimizing a protocol for performing whole-animal ChIP, a technique that to date has not been extensively performed for C. elegans. Using a functional GFP-tagged NHR-6 fusion, we have been successful in initial attempts to IP NHR-6-bound DNA. Additionally, we have also generated the necessary genetic reagents (stable transgenic lines) for the analysis. Additional IP experiments are underway with the goal of analyzing the DNA using ChIP-seq. A long-term plan for this study will be to use these approaches to identify proliferation- and differentiation-specific NHR-6 target genes. For the second specific aim, we have established an RNAi-based genetic interaction screen. The screen is a combinatorial approach where RNAi against nhr-6 is combined with RNAi against candidate signaling genes. The screen is underway and has identified candidate interactors. We plan to identify and characterize these candidate signaling pathways with the goal of identifying proteins that regulate distinct activities of NHR-6.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-7 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Louisiana State University A&M Col Baton Rouge
Schools of Veterinary Medicine
Baton Rouge
United States
Zip Code
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

Showing the most recent 10 out of 179 publications