Raquel Sitcheran
Assistant Professor
Department of Molecular and Cellular Medicine
Room 105 Reynolds Medical Building
College Station,
Texas 77843
Phone: (979) 845-6353
Fax: (979) 847-9481
Email: sitcheran@medicince.tamhsc.edu
Lab Webpage: http://sitcheranlab.wordpress.com/
Education and Post-Graduate Training
Research Interests
The goal of our research is to understand the molecular mechanisms that control NF-κB regulatory networks in the central nervous system (CNS). NF-κB is a ubiquitously expressed, evolutionarily conserved transcription factor that responds to a variety of signals and regulates fundamental processes, including cell growth and proliferation, inflammation, invasion and angiogenesis. Indeed, aberrant NF-κB activity or expression is associated with many cancers, as it can promote tumorigenesis, tumor progression and resistance to therapy. Our focus is on glioblastoma, a common and highly lethal CNS tumor that is very resistant to current treatment strategies. Previously, we demonstrated that in glioblastoma cells, signaling crosstalk between metabotropic glutamate receptors and EGFR leads to increased activation of NF-κB. We are taking a multidisciplinary approach to investigate how different signals regulate NF-κB and how de-regulation of the NF-κB pathway impacts cancer cell growth, self-renewal and survival.
Specifically, we are employing 1) biochemical, cellular and molecular strategies to compare how different signals regulate NF-κB activity in normal neural cells and cancer cells, 2) bioinformatics analysis of NF-κB-dependent genes and microRNAs involved in glioblastoma survival and pathogenesis, and 3) mouse models to investigate NF-κB signaling in glioblastoma and normal neural cells in vivo.
Our studies are relevant to understanding the role of NF-κB in both normal and cancer stem cells and will facilitate identifying components of this regulatory network that can be targeted for therapeutic strategies of glioblastoma, as well as other diseases.
Selected Publications
Comb WC, Cogswell P, Sitcheran R, Baldwin AS. IKK-dependent, NF-κB-independent control of autophagic gene expression. Oncogene. 2011 Apr 7;30(14):1727-32. Epub 2010 Dec 13. PMID: 21151171
Ex vivo inhibition of NF-kappaB signaling in alloreactive T-cells prevents graft-versus-host disease. Am J Transplant. 2009 Mar;9(3):452-62. O'Shaughnessy MJ, Vogtenhuber C, Sun K, Sitcheran R, Baldwin AS, Murphy WJ, Dang L, Jaffee B, Palmer E, Serody JS, Blazar BR. PMID: 19260829
Blimp-1/PRDM1 mediates transcriptional suppression of the NLR gene NLRP12/Monarch-1. J Immunol. 2009 Mar 1;182(5):2948-58. Lord CA, Savitsky D, Sitcheran R, Calame K, Wright JR, Ting JP, Williams KL. PMID: 19234190
Sitcheran, R., Comb, W.C., Cogswell, P.C., and Baldwin, A.S. (2008) Essential role for epidermal growth factor receptor in glutamate receptor signaling to NF-kappaB. Mol Cell Biol. 28(16):5061-5070. Epub 2008 Jun 9.
Steinbrecher, K.A., Harmel-Laws, E., Sitcheran, R., and Baldwin, A.S. (2008) Loss of epithelial RelA results in deregulated intestinal proliferative/apoptotic homeostasis and susceptibility to inflammation. J Immunol. 180(4):2588-2599.
Sitcheran, R., Gupta, P., Fisher, P.B., and Baldwin, A.S. (2005) Positive and negative regulation of EAAT2 by NF-kappaB: a role for N-myc in TNFalpha-controlled repression. EMBO J. 24(3):510-520. Epub 2005 Jan 20.
Loercher, A., Lee, T.L., Ricker, J.L., Howard, A., Geoghegen, J., Chen, Z., Sunwoo, J.B., Sitcheran, R., Chuang, E.Y., Mitchell, J.B., Baldwin, A.S. Jr, and Van Waes. C. (2004) Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma.Cancer Res. 64(18):6511-6523. Erratum in: Cancer Res. 2004 Nov 1; 64(21):8130-8132.
Sitcheran R., Cogswell P., Baldwin, A.S. (2003). NF-kappaB mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism. Genes & Development. 17(19):2368-2373.
