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Faculty Detail    
Name SUSAN E NOZELL
Assistant Professor
 
Campus Address MCLM 310 Zip 0005
Phone 205-996-9468
E-mail snozell@uab.edu
Other websites
     

Education
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  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Assistant Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Assistant Professor
Center  Medicine  Ctr Cardiovasc Bio Assistant Professor

Society Memberships
Organization Name Position Held Org Link
American Association of Cancer Research    http://www.aacr.org 
American Society of Cell Biology    http://www.ascb.org 
Society for NeuroOncology    http://www.soc-neuro-onc.org/ 

Research/Clinical Interest
Title
Role of Inflammation and Inflammatory Mediators in the Pathogenesis of Glioblastoma
Description
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.
 
18779315 
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.
 
19668231 
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.
 
20367209 
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.
 
20870728 
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.
 
21279667 
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.
 
22027691 
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.
 
23226414  
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  

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