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Lyse A. Norian, PhD

Lyse Norian, PhD
 
Associate Professor
Department of Nutrition Sciences
WTI 320C
Phone: 996-0152
Email: lnorian@uab.edu
Full CV

Dr. Norian is an Associate Professor in the Department of Nutrition Sciences. She performed her doctoral research in the laboratory of Dr. Gary Koretzky at the University of Iowa, where she studied transcriptional regulation of the pro-apoptotic molecule Fas Ligand on CD8+ T cells. She then moved to the Washington University School of Medicine in St. Louis, where she studied tumor-induced T cell and dendritic cell dysfunction as a post-doctoral fellow in the laboratory of Dr. Paul Allen. Upon completion of her training, Dr. Norian was recruited back to the University of Iowa, where she was promoted to Assistant Professor and began to study the effects of obesity on immune responses to renal tumors in the Department of Urology.

Current Research Interests:

Immune-based therapies have shown tremendous clinical potential for treating advanced cancers in a subset of patients, but their broad clinical efficacy remains limited. As obesity is a known risk factor for increased cancer prevalence and mortality, it is critical to understand how obesity impacts anti-tumor immunity and immunotherapeutic efficacy. A major research focus in my lab is investigating how immune responses to solid tumors change in the presence of chronic, diet-induced obesity. We have found that in mice with renal tumors, obesity impairs protective anti-tumor immunity and leads to immunotherapeutic failure. We are now identifying the mechanistic basis for this failure, and have already described obesity-dependent defects in CD8+ T cells, dendritic cells, and myeloid-derived suppressor cells in mice with renal tumors. To better understand the broad applicability of our findings, we are extending our studies into murine models of metastatic breast cancer. In addition, we have begun to investigate the ways in which obesity alters immune responses in renal cancer patients. Finally, as our long-term goal is to apply the fundamental knowledge gained during the course of these studies into novel, immune-based therapies for advanced cancer patients, we also have an active line of research that seeks to develop new combinatorial immunotherapies for metastatic cancers. Our pre-clinical studies in this area use in vivo imaging of localized and disseminated tumor cells in lean and obese mice to track therapeutic responses in real time.

Publications

  1. LA Norian and RF Rosenbusch.  “Mycoplasma bovoculi-augmented bovine natural killer activity.”  Comp. Immunol. Microbiol. Infect. Dis.  1993. 16(2): 113-22.
     
  2. KM Latinis, LL Carr, EJ Peterson, LA Norian, SL Eliason, and GA Koretzky.  “Regulation of CD95 (Fas) ligand expression by TCR-mediated signaling events.”  J. Immunology.  1997. 158: 4602-4611.
     
  3. KM Latinis, LA Norian, SL Eliason, and GA Koretzky.  “Two NFAT transcription factor binding sites participate in the regulation of CD95 (Fas) ligand expression in activated T cells.”  J. Biological Chemistry.  1997. 272: 31427-31434.
     
  4. LA Norian, KM Latinis, and GA Koretzky.  “A newly identified response element in the CD95 (Fas) ligand promoter contributes to optimal inducibility in activated T lymphocytes.”  J. Immunology.  1998. 161: 1078-1082.
     
  5. JS Cowdery, NJ Boerth, LA Norian, PS Myung, and GA Koretzky.  “Differential regulation of the IL-12 p40 promoter and of p40 secretion by CpG DNA and lipopolysaccharide.”  J. Immunology.  1999. 162: 6770-6775.
     
  6. LA Norian and GA Koretzky.  “TCR-induced signaling for cytotoxicity: the regulation of CD95L (Fas ligand) expression in activated T lymphocytes.” In Cytotoxic Cells: Basic Mechanisms and Medical Applications.  MV Ditovsky and PA Henkart, eds. Lippincott Williams and Wilkins, Philadelphia, 1999, pp.229-239.
     
  7. LA Norian and GA Koretzky.  “Intracellular Adapter Molecules.”  Sem. Immunol.  2000. 12: 43-54.
     
  8. LA Norian, KM Latinis, SL Eliason, K Lyson, C Yang, T Ratliff, and GA Koretzky.  “The regulation of CD95 (Fas) ligand expression in primary T cells: induction of promoter activation in CD95LP-Luc transgenic mice.”  J. Immunology.  2000. 164: 4471-4480.
     
  9. LA Norian and GA Koretzky.  “Lymphocyte signaling.” In Samter’s Immunologic Diseases.  KF Austin, MM Frank, JP Atkinson, and H Cantor, eds.  Lippincott Williams and Wilkins, Philadelphia, 2001, pp. 82-93.
     
  10. HL Hanson, SS Kang, LA Norian, K Matsui, LA O’Mara, and PM Allen.  “CD4-directed peptide vaccination augments an antitumor response, but efficacy is limited by the number of CD8+ T cell precursors.”  J. Immunology.  2004. 172: 4215-4224.
     
  11. LA Norian and PM Allen.  “No intrinsic deficiencies in CD8+ T cell-mediated antitumor immunity with aging.”  J. Immunology.  2004.  173: 835-844.
     
  12. LA O’Mara, LA Norian, D. Kreamalmeyer, JM White, and PM Allen.  “T cell mediated delay of spontaneous mammary tumor onset: Increased efficacy with in vivo versus in vitro activation.”  J. Immunology.  2005.  174: 4662-4669.
     
  13. LA Norian and PM Allen.  “Rapid maturation of effector T cells in tumors, but not lymphoid organs, during tumor regression” PLoS ONE.  2007.  2(9): e821.  doi:10.1371/journal.pone.0000821.
     
  14. SS Kang, SM Bloom, LA Norian, MJ Geske, RA Flavell, TS Stappenbeck and PM Allen.  “An antibiotic responsive mouse model of fulminant ulcerative colitis”  PLoS Medicine.  2008. 5(3): e41. 
     
  15. LA Norian, LA O’Mara, PC Rodriguez, J Zabaleta, A Ochoa, M Cella, and PM Allen.  “Tumor-infiltrating regulatory dendritic cells suppress CD8+ T cell function via L-arginine metabolism.”  Cancer Research.  2009. 69(7):3086-94. PMID: 19293186.
     
  16. TS Griffith, B Stokes, TA Kucaba, JK Earel Jr., RL vanOosten, EL Brincks, and LA Norian. “TRAIL gene therapy: From pre-clinical development to clinical application.”  Current Gene Therapy. 2009. 9(1): 9-19. PMID: 19275567
     
  17. LA Norian, JK Earel Jr., TA Kucaba, T Knutson, RL vanOosten, and TS Griffith.  “Synergistic induction of apoptosis in primary B-CLL cells after treatment with recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Histone Deacetylase Inhibitors.”  J. Oncology. 2009: 408038. PMID: 19547714.
     
  18. LA Norian, BR James, and TS Griffith. “Advances in viral vector-based TRAIL gene therapy for cancer.” Cancers. 2011. 3: 603-620.
     
  19. LA Norian, TP Kresowik, HM Rosevear, AJ Lightfoot, TA Kucaba, TR Rosean, BR James, C Schwarz, CJ Weydert, MD Henry, and TS Griffith.  “Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF-related apoptosis-inducing ligand (TRAIL) /CpG immunotherapy.” PLoS ONE. 2012: 7(2):e31085. PMID: 22312440.
     
  20. BR James, TA Kucaba, TS Griffith, and LA Norian.  “Diet-induced obesity alters dendritic cell function in the presence and absence of tumor growth.”  J. Immunology.  2012. 189(3): 1311-21. PMID: 22745381.
     
  21. G Wald, KT Barnes, MT Bing, TP Kresowik, A Tomanek-Chalkley, T Kucaba, TS Griffith, JA Brown, LA Norian.Minimal changes in the systemic immune response after nephrectomy of localized renal masses.”  2014. Urologic Oncology. 32(5): 589-600. PMID: 24768357. ** Note: article featured on the Uro Today website, an internet-based Urology News and Education Resource for clinicians and researchers.
     
  22. BR James, KG Anderson, EL Brincks, TA Kucaba, LA Norian, D Masopust, TG Griffith.  “CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy.”  2014.  Cancer Immunology, Immunotherapy. 63(11):1213-1227. PMID: 25143233.
     
  23. VB Joshi, BP Gross, SM Geary, A Wongrakpanich, LA Norian*, AK Salem*. “Tumor lysate loaded biodegradable particles as cancer vaccines.” Commissioned Review for Expert Review of Vaccines. 2014. 13(1): 9-15. PMID: 24219096 *Co-corresponding authors.
     
  24. BP Gross, A Wongrakpanich, MB Francis, AK Salem, LA Norian. “A therapeutic microparticle-based tumor lysate vaccine reduces spontaneous metastases in murine breast cancer.”  2014.  The American Association of Pharmaceutical Sciences Journal.  16(6):1194-1203. PMID: 25224145.
     
  25. SH Khan, EA Hemann, KL Legge, LA Norian, VP Badovinac.  “Diet-induced obesity does not impact the generation or maintenance of memory CD8 T cells.” 2014. J. Immunology.  193(12):5873-5882. PMID: 25378592.
     
  26. BM Schickling, AK England, N Aykin-Burns, LA Norian, KK Leslie, VP Freiden-Korovkina. “BKCa channel inhibitor modulates the tumorigenic ability of hormone-independent breast cancer cells via the Wnt pathway.” 2014.  Oncology Reports. doi: 10.3892/or.2014.3617.  PMID: 25422049.
     
  27. V Chehval and LA Norian.  “Effects of obesity on immune responses to renal tumors.”  Invited review for Immunologic Research.  2014. 59(103): 211-219. PMID: 24838144.
     
  28. TR Rosean, VS Tompkins, AK Olivier, R Sompallae, LA Norian, HC Morse III, TJ Waldschmidt, S Janz.  “The tumor microenvironment is the main source of IL-6 for plasma cell tumor development in mice.”  2015.  Leukemia. 29(1):233-7. PMID: 25257990.  
     
  29. M Hale, F Itani, G Wald, A Tomanek-Chalkley, M Bing, LA Norian.  “Obesity triggers enhanced MDSC accumulation in renal tumors via elevated local production of CCL2.” 2015.  PLoS ONE.  Mar 13;10(3):e0118784. PMID: 25769110.
     
  30. MT Kim, MJ Richer, BP Gross, LA Norian, VP Badovinac, JT Harty.  “Enhancing dendritic cell-based immunotherapy with IL-2/mAB complexes for control of established tumors.”  2015. J. Immunology.  Nov 1; 195(9):4537-44. PMID: 26408669.
     
  31. SK Boi*, CM Buchta*, NA Pearson, MB Francis, D Meyerholz, JL Grobe, and LA Norian.  “Obesity alters immune and metabolic profiles: new insight from obese-resistant mice.”  2016. Obesity.  Aug 12 doi: 10.1002/oby.21620.  Featured article on Obesity and Energetics Offerings.
     
  32. ER Craig, AI Londono, LA Norian, and RC Arend.  “Metabolic risk factors and mechanisms of disease in epithelial ovarian cancer: A review.” 2016. Gynecologic Oncology. Dec;143(3):674-683. PMID: 27751590
     
  33. AM Janowski, OC Colegio, Em Hornick, JM McNiff, MD Martin, VP Badovinac, LA Norian, W Zhang, SL Cassel, and FS Sutterwala.  “Inflammasome-independent role of NLRC4 in suppressing melanoma progression.”  2016. Journal of Clinical Investigation.  2016 Oct 3;126(10):3917-3928. PMID: 27617861.
     
  34. RM Orlandella and LA Norian.  “Obesity-induced defects in dendritic cell and T cell functions: implications for immunotherapeutic efficacy.”  Invited book Chapter for Immunology, Volume 1. Elsevier/Academic Press. Eric Hayat, Editor. 2017. In press.
     
  35. CM Tobert, JM Hamilton-Reeves, LA Norian, C Hung, NA Brooks, JM Hozbeierlein, TM Downs, DP Robertson, R Grossman, KG Nepple. The emerging impact of malnutrition on surgical patients: literature review and potential implications on cystectomy for bladder cancer. 2017.  Journal of Urology. Mar 9. pii: S0022-5347(17)39247-9. doi: 10.1016/j.juro.2017.01.087.
     
  36. CM Buchta*, SK Boi*, BJ Miller, MM Milhem, and LA Norian.  “Obesity does not exacerbate the pro-tumorigenic systemic environment in sarcoma subjects.”  2017. ImmunoHorizons.1:20-28.
     
  37. TB Turner, S Mesa-Perez, A Londono, A Katre, LA Norian, DJ Buchsbaum, JM Straughn, A Forero, AF LoBuglio, TD Randall, and RC Arend.  “Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth.”  2017.  Oncotarget. 2017 Apr 24. doi: 10.18632/oncotarget.17395.
     
  38. LA Bertrand, LJ Thomas, P Li, CM Buchta, SK Boi, RM Orlandella, JA Brown, KG Nepple, and LA Norian.  “Obesity as defined by waist circumference but not body mass index is associated with higher renal mass complexity” 2017.  Urologic Oncology. doi: 10.1016/j.urolonc.2017.06.058. [Epub ahead of print]. PMID:28797586. ** Note: article featured on the Uro Today website, an internet-based Urology News and Education Resource for clinicians and researchers.
     
  39. W Demark-Wahnefried, S Rais-Bahrami, RA Desmond, JB Gordetsky, GR Hunter, ES Yang, M Azrad, AD Fruge, JW Nix, S Sudarshan, Y Tsruta, LA Norian, SA Tully, R Segal, and WE Grizzle. “Effects of a pre-surgical weight loss intervention on tumor characteristics and circulating biomarkers in men with prostate cancer.”  2017. British Journal of Cancer.  In press.
     
  40. HJ Smith, TR McCaw, AI Londono, AA Katre, S Meza-Perez, A Forero, DJ BUchsbaum, TD Randall, JM Straughn, Jr., LA Norian, and RC Arend. “The anti-tumor effects of entinostat in ovarian cancer require adaptive immunity.” 2017. Submitted.
     
  41. H Sadahiro, KD Kang, SYamaguchi, M Minata, J Wang, J Shi, LA Norian, EW Newell, D Hambardzumyan, B DasGupta, M Nakada, LJ Lee, B Nabors, and I Nakano. “Activation of the receptor tyrosine kinase AXL mediates the immune microenvironment in glioblastoma.” 2017. Submitted.
     
  42. SJ Carter, GR Hunter, LA Norian, B Turan, LQ Rogers.  “Ease of walking associates with greater free-living physical activity and reduced depressive symptomology in breast cancer survivors: pilot randomized trial.” 2017. Submitted.
     
  43. SK Boi, RM Orlandella, JT Gibson, LA Norian. “Endogenous T cell priming upstream of checkpoint blockade enhances tumor clearance in lean but not obese mice.” 2017. In preparation.
     
  44. KE Norris, G Wald, LJ Thomas, CM Buchta, LA Bertrand, SK Boi, AS Salem, D Lubaroff, KG Nepple, JA Brown, and LA Norian.  “Obesity induces selective changes in the immune landscape in human renal cell carcinoma subjects.” 2017.  In preparation.