Vanderbilt-Ingram Cancer Center

The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers

Fiona Elizabeth Yull, D.Phil.

Assistant Professor of Cancer Biology

Contact Information:

Vanderbilt-Ingram Cancer Center
2220 Pierce Ave., PRB 769
Nashvill, TN 37232-6840
615-343-2568
Fax: 615-343-2569

Research Specialty:

Generation of mouse models to investigate NF-kappaB in development and disease

Research Description:

The NF-kappaB family of transcription factors are regulators of many critical processes such as proliferation, apoptosis, immune responses and inflammation. It is, therefore, unsurprising that they play roles in basic development but also in most diseases including cancer. Our laboratory has generated a number of mouse models to investigate these roles in development; breast, lungs, limbs and immune system. We are also interested in the roles played by NF-kappaB signaling in disease. We are currently primarily interested in breast and lung cancer. We have generated a number of interesting models that we use for our research. Our new transgenic reporter mice express a GFP/luciferase fusion protein that can emit light in response to NF-kappaB activity. With these we can monitor activation in a living animal using a CCD camera and use immunohistochemical techniques to identify specific cell types in which NF-kappaB is active. We have also generated a modular inducible system that enables us to turn up or down NF-kappaB activity in specific cell types. Finally, we have two models in which we are analysing effects that resemble early stages of breast tumor development and determining the effects of modulating NF-kappaB activity on primary mammary tumor development and metastasis.

Publications:

• Singh, MV, Kapoun, A, Higgins, L, Kutschke, W, Thurman, JM, Zhang, R, Singh, M, Yang, J, Guan, X, Lowe, JS, Weiss, RM, Zimmermann, K, Yull, FE, Blackwell, TS, Mohler, PJ, Anderson, ME Ca2+/calmodulin-dependent kinase II triggers cell membrane injury by inducing complement factor B gene expression in the mouse heart. J Clin Invest, 119(4), 986-96, 2009.
• Han, W, Joo, M, Everhart, MB, Christman, JW, Yull, FE, Blackwell, TS Myeloid cells control termination of lung inflammation through the NF-kappaB pathway. Am J Physiol Lung Cell Mol Physiol, 296(3), L320-7, 2009.
• Stathopoulos, GT, Sherrill, TP, Han, W, Sadikot, RT, Yull, FE, Blackwell, TS, Fingleton, B Host nuclear factor-kappaB activation potentiates lung cancer metastasis. Mol Cancer Res, 6(3), 364-71, 2008.
• Chen, SM, Cheng, DS, Williams, BJ, Sherrill, TP, Han, W, Chont, M, Saint-Jean, L, Christman, JW, Sadikot, RT, Yull, FE, Blackwell, TS The nuclear factor kappa-B pathway in airway epithelium regulates neutrophil recruitment and host defence following Pseudomonas aeruginosa infection. Clin Exp Immunol, 2008.
• Jin, RJ, Lho, Y, Connelly, L, Wang, Y, Yu, X, Saint Jean, L, Case, TC, Ellwood-Yen, K, Sawyers, CL, Bhowmick, NA, Blackwell, TS, Yull, FE, Matusik, RJ The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth. Cancer Res, 68(16), 6762-9, 2008.
• Stathopoulos, GT, Sherrill, TP, Han, W, Sadikot, RT, Polosukhin, VV, Fingleton, B, Yull, FE, Blackwell, TS Use of bioluminescent imaging to investigate the role of nuclear factor-kappaBeta in experimental non-small cell lung cancer metastasis. Clin Exp Metastasis, 25(1), 43-51, 2008.
• Connelly, L, Robinson-Benion, C, Chont, M, Saint-Jean, L, Li, H, Polosukhin, VV, Blackwell, TS, Yull, FE A transgenic model reveals important roles for the NF-kappa B alternative pathway (p100/p52) in mammary development and links to tumorigenesis. J Biol Chem, 282(13), 10028-35, 2007.
• Cheng, DS, Han, W, Chen, SM, Sherrill, TP, Chont, M, Park, GY, Sheller, JR, Polosukhin, VV, Christman, JW, Yull, FE, Blackwell, TS Airway epithelium controls lung inflammation and injury through the NF-kappa B pathway. J Immunol, 178(10), 6504-13, 2007.
• Park, GY, Hu, N, Wang, X, Sadikot, RT, Yull, FE, Joo, M, Stokes Peebles, R, Blackwell, TS, Christman, JW Conditional regulation of cyclooxygenase-2 in tracheobronchial epithelial cells modulates pulmonary immunity. Clin Exp Immunol, 150(2), 245-54, 2007.
• Stathopoulos, GT, Sherrill, TP, Cheng, DS, Scoggins, RM, Han, W, Polosukhin, VV, Connelly, L, Yull, FE, Fingleton, B, Blackwell, TS Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Proc Natl Acad Sci U S A, 104(47), 18514-9, 2007.
• Everhart, MB, Han, W, Sherrill, TP, Arutiunov, M, Polosukhin, VV, Burke, JR, Sadikot, RT, Christman, JW, Yull, FE, Blackwell, TS Duration and intensity of NF-kappaB activity determine the severity of endotoxin-induced acute lung injury. J Immunol, 176(8), 4995-5005, 2006.
• Stathopoulos, GT, Zhu, Z, Everhart, MB, Kalomenidis, I, Lawson, WE, Bilaceroglu, S, Peterson, TE, Mitchell, D, Yull, FE, Light, RW, Blackwell, TS Nuclear Factor-{kappa}B Affects Tumor Progression in a Mouse Model of Malignant Pleural Effusion. Am J Respir Cell Mol Biol, 34(2), 142-150, 2006.
• Stafforini, DM, Sheller, JR, Blackwell, TS, Sapirstein, A, Yull, FE, McIntyre, TM, Bonventre, JV, Prescott, SM, Roberts, LJ Release of free F2-isoprostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet-activating factor acetylhydrolases. J Biol Chem, 281(8), 4616-23, 2006.
• Sadikot, RT, Zeng, H, Joo, M, Everhart, MB, Sherrill, TP, Li, B, Cheng, DS, Yull, FE, Christman, JW, Blackwell, TS Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa. J Immunol, 176(8), 4923-30, 2006.
• Everhart, MB, Han, W, Parman, KS, Polosukhin, VV, Zeng, H, Sadikot, RT, Li, B, Yull, FE, Christman, JW, Blackwell, TS Intratracheal administration of liposomal clodronate accelerates alveolar macrophage reconstitution following fetal liver transplantation. J Leukoc Biol, 77(2), 173-80, 2005.
• O''Donnell, SM, Hansberger, MW, Connolly, JL, Chappell, JD, Watson, MJ, Pierce, JM, Wetzel, JD, Han, W, Barton, ES, Forrest, JC, Valyi-Nagy, T, Yull, FE, Blackwell, TS, Rottman, JN, Sherry, B, Dermody, TS Organ-specific roles for transcription factor NF-kappaB in reovirus-induced apoptosis and disease. J Clin Invest, 115(9), 2341-50, 2005.
• Ponnappan, U, Yull, FE, Soderberg, LS Inhaled isobutyl nitrite inhibited macrophage inducible nitric oxide by blocking NFkappaB signaling and promoting degradation of inducible nitric oxide synthase-2. Int Immunopharmacol, 4(8), 1075-82, 2004.
• Schneider, C, Strayhorn, WD, Brantley, DM, Nanney, LB, Yull, FE, Brash, AR Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice. J Invest Dermatol, 122(3), 691-8, 2004.
• Sadikot, RT, Zeng, H, Yull, FE, Li, B, Cheng, DS, Kernodle, DS, Jansen, ED, Contag, CH, Segal, BH, Holland, SM, Blackwell, TS, Christman, JW p47phox deficiency impairs NF-kappa B activation and host defense in Pseudomonas pneumonia. J Immunol, 172(3), 1801-8, 2004.
• Yull, FE, Han, W, Jansen, ED, Everhart, MB, Sadikot, RT, Christman, JW, Blackwell, TS Bioluminescent detection of endotoxin effects on HIV-1 LTR-driven transcription in vivo. J Histochem Cytochem, 51(6), 741-9, 2003.
• Sadikot, RT, Han, W, Everhart, MB, Zoia, O, Peebles, RS, Jansen, ED, Yull, FE, Christman, JW, Blackwell, TS Selective I kappa B kinase expression in airway epithelium generates neutrophilic lung inflammation. J Immunol, 170(2), 1091-8, 2003.
• Gray, KD, Simovic, MO, Chapman, WC, Blackwell, TS, Christman, JW, Washington, MK, Yull, FE, Jaffal, N, Jansen, ED, Gautman, S, Stain, SC Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis. J Surg Res, 110(1), 310-4, 2003.
• Sadikot, RT, Wudel, LJ, Jansen, DE, Debelak, JP, Yull, FE, Christman, JW, Blackwell, TS, Chapman, WC Hepatic cryoablation-induced multisystem injury: bioluminescent detection of NF-kappaB activation in a transgenic mouse model. J Gastrointest Surg, 6(2), 264-70, 2002.
• Sadikot, RT, Jansen, ED, Blackwell, TR, Zoia, O, Yull, F, Christman, JW, Blackwell, TS High-dose dexamethasone accentuates nuclear factor-kappa b activation in endotoxin-treated mice. Am J Respir Crit Care Med, 164(5), 873-8, 2001.
• Bushdid, PB, Chen, CL, Brantley, DM, Yull, F, Raghow, R, Kerr, LD, Barnett, JV NF-kappaB mediates FGF signal regulation of msx-1 expression. Dev Biol, 237(1), 107-15, 2001.
• Brantley, DM, Chen, CL, Muraoka, RS, Bushdid, PB, Bradberry, JL, Kittrell, F, Medina, D, Matrisian, LM, Kerr, LD, Yull, FE Nuclear factor-kappaB (NF-kappaB) regulates proliferation and branching in mouse mammary epithelium. Mol Biol Cell, 12(5), 1445-55, 2001.
• Hao, CM, Yull, F, Blackwell, T, K??mhoff, M, Davis, LS, Breyer, MD Dehydration activates an NF-kappaB-driven, COX2-dependent survival mechanism in renal medullary interstitial cells. J Clin Invest, 106(8), 973-82, 2000.
• Brantley, DM, Yull, FE, Muraoka, RS, Hicks, DJ, Cook, CM, Kerr, LD Dynamic expression and activity of NF-kappaB during post-natal mammary gland morphogenesis. Mech Dev, 97(1-2), 149-55, 2000.
• Chen, CL, Singh, N, Yull, FE, Strayhorn, D, Van Kaer, L, Kerr, LD Lymphocytes lacking I kappa B-alpha develop normally, but have selective defects in proliferation and function. J Immunol, 165(10), 5418-27, 2000.
• Muraoka, RS, Bushdid, PB, Brantley, DM, Yull, FE, Kerr, LD Mesenchymal expression of nuclear factor-kappaB inhibits epithelial growth and branching in the embryonic chick lung. Dev Biol, 225(2), 322-38, 2000.
• Blackwell, TS, Yull, FE, Chen, CL, Venkatakrishnan, A, Blackwell, TR, Hicks, DJ, Lancaster, LH, Christman, JW, Kerr, LD Multiorgan nuclear factor kappa B activation in a transgenic mouse model of systemic inflammation. Am J Respir Crit Care Med, 162(3 Pt 1), 1095-101, 2000.
• Sohur, US, Chen, CL, Hicks, DJ, Yull, FE, Kerr, LD Nuclear factor-kappaB/Rel is apoptogenic in cytokine withdrawal-induced programmed cell death. Cancer Res, 60(5), 1202-5, 2000.
• Chen, CL, Yull, FE, Cardwell, N, Singh, N, Strayhorn, WD, Nanney, LB, Kerr, LD RAG2-/-, I kappa B-alpha-/- chimeras display a psoriasiform skin disease. J Invest Dermatol, 115(6), 1124-33, 2000.
• Chen, CL, Yull, FE, Kerr, LD Differential serine phosphorylation regulates IkappaB-alpha inactivation. Biochem Biophys Res Commun, 257(3), 798-806, 1999.
• Blackwell, TS, Yull, FE, Chen, CL, Venkatakrishnan, A, Blackwell, TR, Hicks, DJ, Lancaster, LH, Christman, JW, Kerr, LD Use of genetically altered mice to investigate the role of nuclear factor-kappa B activation and cytokine gene expression in sepsis-induced ARDS. Chest, 116(1 Suppl), 73S-74S, 1999.
• Bushdid, PB, Brantley, DM, Yull, FE, Blaeuer, GL, Hoffman, LH, Niswander, L, Kerr, LD Inhibition of NF-kappaB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis. Nature, 392(6676), 615-8, 1998.
• Clark, AJ, Harold, G, Yull, FE Mammalian cDNA and prokaryotic reporter sequences silence adjacent transgenes in transgenic mice. Nucleic Acids Res, 25(5), 1009-14, 1997.
• Clark, AJ, Iwobi, M, Cui, W, Crompton, M, Harold, G, Hobbs, S, Kamalati, T, Knox, R, Neil, C, Yull, F, Gusterson, B Selective cell ablation in transgenic mice expression E. coli nitroreductase. Gene Ther, 4(2), 101-10, 1997.
• Yull, F, Binas, B, Harold, G, Wallace, R, Clark, AJ Transgene rescue in the mammary gland is associated with transcription but does not require translation of BLG transgenes. Transgenic Res, 6(1), 11-7, 1997.
• Yull, F, Harold, G, Wallace, R, Cowper, A, Percy, J, Cottingham, I, Clark, AJ Fixing human factor IX (fIX): correction of a cryptic RNA splice enables the production of biologically active fIX in the mammary gland of transgenic mice. Proc Natl Acad Sci U S A, 92(24), 10899-903, 1995.
• Yull, FE, Wallace, RM, Clark, AJ Restricted tissue-specific but correct developmental expression mediated by a short human alpha 1AT promoter fragment in transgenic mice. Transgenic Res, 4(1), 70-4, 1995.
• Clark, AJ, Bissinger, P, Bullock, DW, Damak, S, Wallace, R, Whitelaw, CB, Yull, F Chromosomal position effects and the modulation of transgene expression. Reprod Fertil Dev, 6(5), 589-98, 1994.
• Dobson, MJ, Yull, FE, Molina, M, Kingsman, SM, Kingsman, AJ Reconstruction of the yeast 2 micron plasmid partitioning mechanism. Nucleic Acids Res, 16(14B), 7103-17, 1988.