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Faculty Detail    
Associate Professor
Campus Address 176F 2222
Phone  205-975-0521
Other websites

Undergraduate  Clemson University    1997  B.S., Biochemistry 
Graduate  Medical College of Georgia    2001  Ph.D., Biochemistry and Molecular Biology 

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Radiation Oncology   Rad Onc - Preclinical Research Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Associate Professor
Center  Medicine  Ctr Cardiovasc Bio (Org Ret) Associate Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 

Society Memberships
Organization Name Position Held Org Link
American Association of Cancer Research 
American Society of Cell Biology 
Society for NeuroOncology 

Research/Clinical Interest
Role of Inflammation and Inflammatory Mediators in the Pathogenesis of Glioblastoma
Malignant gliomas are an aggressive, neurologically destructive and deadly tumor of the CNS. Glioblastoma (GBM), also known as grade IV astrocytoma, is the most malignant, common and deadly brain tumor, and accounts for ~two-thirds of primary malignant brain tumors in adults. GBMs are incurable by surgical resection alone, as this procedure is often followed by the growth of secondary tumors that are non-responsive to radiation or chemotherapy. Once diagnosed, patients usually succumb within 12 to 18 months. The NF-κB proteins are a family of transcription factors that mediate immune and inflammatory responses. Specifically, NF-κB induces the expression of genes that mediate inflammation, cellular proliferation, resistance to apoptosis, migration and invasion, and angiogenesis. Recently it was demonstrated that manipulations in just NF-κB activity or 3 other key pathways, were sufficient to alter gene expression and drive glioma progression. In GBM, we and others have shown that NF-κB is constitutively activated. MicroRNAs (miRs) are a class of short, single-stranded, non-coding RNA molecules that regulate gene expression. miRs are transcribed in the nucleus, cleaved, exported to the cytosol, and cleaved again before being incorporated into an RNA-induced silencing complex (RISC). The association between the RISC and an mRNA inhibits the translation of target mRNAs and/or promotes their degradation. Many miRs function as tumor suppressors or oncogenes, and the genes encoding miRs are frequently dysregulated in cancer. Currently, at least 4 miRNAs, miR-21, miR-26a, miR-128 and miR-34a, are associated with GBMs, and are present in ~9% of GBM. Mir-31 is a recently characterized orphan microRNA with tumor suppressive properties. The gene encoding miR-31, MIR31HG, is located at chromosomal position 9p21.3, adjacent to three tumor suppressor genes: CDKN2B (p15/INK4B) and the CDKN2A locus, which encodes both INK4A/p16 and ARF/p14. Homozygous deletion of the CDKN2A locus is the most frequent chromosomal number variation (CNV) (>65%) within GBMs. We have determined that miR-31 is homozygously co-deleted with CDKN2A in >37% of GBMs, and that >70% of all GBM lose at least 1 copy of miR-31HG. In GBM, reduced miR-31 levels are part of a 10 miR expression signature that correlates with poor patient prognosis and independently predicts patient survival. Currently, we are investigating a) the molecular mechanisms underlying miR-31 dysregulation GBM, b) the mode(s) of miR-31 mediated tumor suppression and c) the function of additional dysregulated microRNAs in the pathogenesis of GBM. Ultimately, we would like to understand how microRNAs impact the activities of NF-kB and other inflammatory mediators and processes in the development and progression of GBM.

Selected Publications 
Publication PUBMEDID
Nozell, S., Laver, T., Moseley, D., Nowaslowski, L., DeVos, M., Atkinson, G. P., Harrison, K., Nabors, L.B., and Benveniste, E. N. 2008. The ING4 tumor suppressor attenuates NF-kB signaling at the promoter of target genes. Mol Cell Biol. 28: 6632-6645.
Atkinson, G. P., Nozell, S. E., Harrison, K., Stonecypher, M., and Benveniste, E. N. 2009. The prolyl isomerase Pin1 regulates the NF-kB signaling pathway and IL-8 expression in glioblastomas. Oncogene. 28: 3735-45.
Atkinson, G. P., Nozell, S. E., and Benveniste, E. N. 2010. NF-kB and STAT3 signaling in glioma: targets for future therapies. Expert Rev Neurother. 10: 575-86.
Olivia, C. R., Nozell, S., Diers, A., McClugage, S. G. 3rd, Sarkaria, J. N., Markert, J. M., Darley-Usmar, V. M., Bailey, S. M., Gillespie, G. Y., Landar, A., and Griguer, C. E. 2010. Acquisition of temozolomide chemoresistance in gliomas leads to remodeling of mitochondrial electron transport chain. J Biol Chem. 285: 39579-67.
Zhao, X., Laver, T., Hong, S., DeVos, A., Twitty, G., DeVos, M., Benveniste, E. N., and Nozell, S. E. 2011. An NF-kB p65-cIAP2 link is necessary for mediating apoptotic resistance to TNF-a in gliomas. J Neurooncol. 102: 367-81.
McFarland, B. C., Ma, J. Y., Langford, C. P., Gillespie, G. Y., Yu, H., Zheng, Y., Nozell, S. E., Huszar, D., and Benveniste, E. N. 2011. Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther. 10(12): 2384-93.
Park, K. W., Nozell, S. E., and Benveniste, E. N. 2012. Protective role of STAT3 in NMDA and glutamate-induced neuronal death: negative regulatory effect of SOCS3. PLoS One. 7(11) e50874.
McFarland, B. C., Hong, S. W., Rajbhandari, R., Twitty, G. B., Gray, G. K., Yu, H., Benveniste, E. N., and Nozell, S. E. 2013. NF-kB-induced IL-6 ensures STAT3 activation and tumor aggressiveness in glioblastoma. PLosOne. 8(11): e78728.  24244348  
Rajbhandari, R., McFarland, B.C., Patel, A., Gerigk, M., Gray, G.K., Fehling, S.C., Bredel, M., Berbari, N.F., Kim, H., Marks, M.P., Meares, G.P., Sinha, T., Chuang, J., Benveniste, E.N., Nozell, S.E. 2015. Loss of tumor suppressive microRNA-31 enhances TRADD/NF-kB signaling in glioblastoma. Oncotarget. 6(19): 17805-16.  26164206 

Glioblastoma, NF-kappaB, microRNA, signal transduction, epigenetics, gene expression