Raquel Sitcheran, PhD
Education and Post-Graduate Training
Dr. Raquel Sitcheran received her Bachelor of Arts in biology from Columbia University in 1992 and her PhD in physiology and genetics from the University of California, San Francisco in 2000 working with Dr. Keith Yamamoto. Her postdoctoral work was with Dr. Albert Baldwin at the University of North Carolina, Chapel Hill. She was a research associate at the Lineberger Comprehensive Cancer Center at UNC Chapel Hill from 2006 to 2009 before joining the faculty at the Texas A&M College of Medicine in September 2009.
A key feature of all aggressive tumors, such as high-grade gliomas, is their ability to invade healthy tissue. Indeed, the infiltrative growth of cancer cells is a major impediment to efficacious treatment. We study the role of NF-κB regulatory proteins in regulating cancer cell behavior, particularly how they acquire motility and invasive potential. 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. Aberrant NF-κB activity or expression is associated with many cancers, as it can promote tumorigenesis, tumor progression and resistance to therapy. We are taking interdisciplinary approaches in cell imaging, in vitro 3-D invasion assays, biochemistry and animal models to study how different signals regulate NF-κBNF-κB and how de-regulation of the NF-κB pathway impacts cancer cell growth, self-renewal and survival.
NF-κB-inducing kinase (NIK) is known to play an important role in immunity, and misregulation of NIK has been associated with many hematological and solid cancers. However, although NIK is expressed in the brain, its role in the CNS in general, and in brain tumors specifically, is poorly understood. My laboratory has established a critical role for NIK and noncanonical NF-κB signaling in promoting the migratory and invasive potential of glioma cells. More recently, we made the novel and intriguing observation that NIK is localized to mitochondria, which are important organelles for cellular energy production and survival. Current research efforts are focused on elucidating mediators of NIK signaling in the mitochondria in both cancer cells and normal, pluripotent cells to gain new insight into how mitochondrial dysfunction contributes to disease and cancer progression.
- Jung JU, Ravi S, Lee DW, McFadden K, Kamradt ML, Toussaint LG, Sitcheran R* (2016). NIK/MAP3K14 regulates mitochondrial dynamics and trafficking to promote cell invasion. Current Biology (In Press)
- Duran CL, Lee DW, Jiung JU, Ravi S, Pogue CB, Toussaint LG, Bayless KJ, Sitcheran R*. (2016). NIK regulates MT1-MMP activity and promotes glioma cell invasion independently of the canonical NF-κB pathway. Oncogenesis, 5(6):e231. PMID: 27270613. http://www.ncbi.nlm.nih.gov/pubmed/27270613
- Cherry EM, Lee DW, Jung JU, Sitcheran R. (2015) Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes glioma cell invasion through induction of NF-kB-inducing kinase (NIK) and noncanonical NF-kB
signaling. Mol Cancer. 14(1):9. [Epub ahead of print] PMID: 25622756. http://www.ncbi.nlm.nih.gov/pubmed/25622756
- Lee DW, Ramakrishnan D, Valenta J, Parney IF, Bayless KJ, SitcheranR. 2013) The NF-κB RelB protein is an oncogenic driver of mesenchymal glioma. PLoS One. 8(2):e57489. doi: 10.1371/journal.pone.0057489. Epub 2013 Feb 25. PMID: 23451236. http://www.ncbi.nlm.nih.gov/pubmed/23451236 http://dx.plos.org/10.1371/journal.pone.0057489
- Comb WC, Cogswell P, Sitcheran R, Baldwin AS. (2011) IKK-dependent, NF-κB-independent control of autophagic gene expression. Oncogene. 30(14):1727-1732. Epub 2010 Dec 13. PMID: 21151171. http://www.ncbi.nlm.nih.gov/pubmed/21151171
- O'Shaughnessy MJ, Vogtenhuber C, Sun K, Sitcheran R, Baldwin AS, Murphy WJ, Dang L, Jaffee B, Palmer E, Serody JS, Blazar BR. (2009) Ex vivo inhibition of NF-kappaB signaling in alloreactive T-cells prevents graft-versus-host disease. Am J Transplant. 9(3):452-462 PMID: 19260829. http://www.ncbi.nlm.nih.gov/pubmed/19260829
- Lord CA, Savitsky D, Sitcheran R, Calame K, Wright JR, Ting JP, Williams KL. (2009) Blimp-1/PRDM1 mediates transcriptional suppression of the NLR gene NLRP12/Monarch-1. J Immunol. 182(5):2948-2958. PMID: 19234190. http://www.ncbi.nlm.nih.gov/pubmed/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. PMID: 18541671. http://www.ncbi.nlm.nih.gov/pubmed/18541671
- 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. PMID: 18250470. http://www.ncbi.nlm.nih.gov/pubmed/18250470
- 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. PMID: 15660126. http://www.ncbi.nlm.nih.gov/pubmed/15660126
- 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. PMID: 15374962. http://www.ncbi.nlm.nih.gov/pubmed/15374962
- 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. PMID: 14522944. http://www.ncbi.nlm.nih.gov/pubmed/14522944