Vanderbilt University School of Medicine

Yull, Fiona Elizabeth , D.Phil.
Associate Professor of Cancer Biology

Lab Url: N/A

Phone Number: 615-343-2568

Email Address:fiona.yull@Vanderbilt.Edu

Yull, Fiona's picture

Office Address   Mailing Address

B3302 MCN (office)/325 PRB (lab)

B3302 Medical Center North 6840

Research Keywords
NF-kappaB, transgenic models, inducible models, breast and lung cancer,Cancer,Knockout,Mouse,Transcription factor

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 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 eg. mammary or lung epithelium or macrophages. We are using multiple models to study the effects of modulating NF-kappaB activity on normal breast development, early stages of primary breast tumor development and on metastasis to the lungs.

Jin, R, Yi, Y, Yull, FE, Blackwell, TS, Clark, PE, Koyama, T, Smith, JA, Matusik, RJ. NF-??B gene signature predicts prostate cancer progression. Cancer Res, 74(10), 2763-72, 2014.

Shi, C, Washington, MK, Chaturvedi, R, Drosos, Y, Revetta, FL, Weaver, CJ, Buzhardt, E, Yull, FE, Blackwell, TS, Sosa-Pineda, B, Whitehead, RH, Beauchamp, RD, Wilson, KT, Means, AL. Fibrogenesis in pancreatic cancer is a dynamic process regulated by macrophage-stellate cell interaction. Lab Invest, 94(4), 409-21, 2014.

Stouch, AN, Zaynagetdinov, R, Barham, WJ, Stinnett, AM, Slaughter, JC, Yull, FE, Hoffman, HM, Blackwell, TS, Prince, LS. I??B Kinase Activity Drives Fetal Lung Macrophage Maturation along a Non-M1/M2 Paradigm. J Immunol, , , 2014.

Edwards, JR, Perrien, DS, Fleming, N, Nyman, JS, Ono, K, Connelly, L, Moore, MM, Lwin, ST, Yull, FE, Mundy, GR, Elefteriou, F. Silent information regulator (Sir)T1 inhibits NF-??B signaling to maintain normal skeletal remodeling. J Bone Miner Res, 28(4), 960-9, 2013.

Han, W, Li, H, Cai, J, Gleaves, LA, Polosukhin, VV, Segal, BH, Yull, FE, Blackwell, TS. NADPH oxidase limits lipopolysaccharide-induced lung inflammation and injury in mice through reduction-oxidation regulation of NF-??B activity. J Immunol, 190(9), 4786-94, 2013.

Li, H, Han, W, Polosukhin, V, Yull, FE, Segal, BH, Xie, CM, Blackwell, TS. NF-??B inhibition after cecal ligation and puncture reduces sepsis-associated lung injury without altering bacterial host defense. Mediators Inflamm, 2013, 503213, 2013.

Yu, SS, Lau, CM, Barham, WJ, Onishko, HM, Nelson, CE, Li, H, Smith, CA, Yull, FE, Duvall, CL, Giorgio, TD. Macrophage-specific RNA interference targeting via "click", mannosylated polymeric micelles. Mol Pharm, 10(3), 975-87, 2013.

Barham, W, Sherrill, T, Connelly, L, Blackwell, TS, Yull, FE. Intraductal injection of LPS as a mouse model of mastitis: signaling visualized via an NF-??B reporter transgenic. J Vis Exp, (67), e4030, 2012.

Zaynagetdinov, R, Stathopoulos, GT, Sherrill, TP, Cheng, DS, McLoed, AG, Ausborn, JA, Polosukhin, VV, Connelly, L, Zhou, W, Fingleton, B, Peebles, RS, Prince, LS, Yull, FE, Blackwell, TS. Epithelial nuclear factor-??B signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes. Oncogene, 31(26), 3164-76, 2012.

Blackwell, TS, Hipps, AN, Yamamoto, Y, Han, W, Barham, WJ, Ostrowski, MC, Yull, FE, Prince, LS. NF-??B signaling in fetal lung macrophages disrupts airway morphogenesis. J Immunol, 187(5), 2740-7, 2011.

Connelly, L, Barham, W, Onishko, HM, Chen, L, Sherrill, TP, Zabuawala, T, Ostrowski, MC, Blackwell, TS, Yull, FE. NF-kappaB activation within macrophages leads to an anti-tumor phenotype in a mammary tumor lung metastasis model. Breast Cancer Res, 13(4), R83, 2011.

Connelly, L, Barham, W, Onishko, HM, Sherrill, T, Chodosh, LA, Blackwell, TS, Yull, FE. Inhibition of NF-kappa B activity in mammary epithelium increases tumor latency and decreases tumor burden. Oncogene, 30(12), 1402-12, 2011.

Lawson, WE, Cheng, DS, Degryse, AL, Tanjore, H, Polosukhin, VV, Xu, XC, Newcomb, DC, Jones, BR, Roldan, J, Lane, KB, Morrisey, EE, Beers, MF, Yull, FE, Blackwell, TS. Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs. Proc Natl Acad Sci U S A, 108(26), 10562-7, 2011.

Zaynagetdinov, R, Sherrill, TP, Polosukhin, VV, Han, W, Ausborn, JA, McLoed, AG, McMahon, FB, Gleaves, LA, Degryse, AL, Stathopoulos, GT, Yull, FE, Blackwell, TS. A critical role for macrophages in promotion of urethane-induced lung carcinogenesis. J Immunol, 187(11), 5703-11, 2011.

Connelly, L, Barham, W, Pigg, R, Saint-Jean, L, Sherrill, T, Cheng, DS, Chodosh, LA, Blackwell, TS, Yull, FE. Activation of nuclear factor kappa B in mammary epithelium promotes milk loss during mammary development and infection. J Cell Physiol, 222(1), 73-81, 2010. PMCID:2783968

Segal, BH, Han, W, Bushey, JJ, Joo, M, Bhatti, Z, Feminella, J, Dennis, CG, Vethanayagam, RR, Yull, FE, Capitano, M, Wallace, PK, Minderman, H, Christman, JW, Sporn, MB, Chan, J, Vinh, DC, Holland, SM, Romani, LR, Gaffen, SL, Freeman, ML, Blackwell, TS. NADPH oxidase limits innate immune responses in the lungs in mice. PLoS One, 5(3), e9631, 2010. PMCID:2838778

Stathopoulos, GT, Sherrill, TP, Karabela, SP, Goleniewska, K, Kalomenidis, I, Roussos, C, Fingleton, B, Yull, FE, Peebles, RS, Blackwell, TS. Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion. Am J Respir Crit Care Med, 182(10), 1273-81, 2010.

Yang, J, Splittgerber, R, Yull, FE, Kantrow, S, Ayers, GD, Karin, M, Richmond, A. Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J Clin Invest, 120(7), 2563-74, 2010. PMCID:2898608

Chiang, SH, Bazuine, M, Lumeng, CN, Geletka, LM, Mowers, J, White, NM, Ma, JT, Zhou, J, Qi, N, Westcott, D, Delproposto, JB, Blackwell, TS, Yull, FE, Saltiel, AR. The protein kinase IKKepsilon regulates energy balance in obese mice. Cell, 138(5), 961-75, 2009. PMCID:2756060

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. PMCID:2660215

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. PMCID:2662543

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. PMCID:2527362

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.

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.

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.

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.

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. PMCID:2219354

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. PMCID:2141808

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.

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.

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.

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. PMCID:2644178

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. PMCID:1184036

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.

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.

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.

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, 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.

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, 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.

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. PMCID:34596

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.

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.

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.

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.

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.

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. PMCID:314340

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.

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.

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.

Chen, CL, Yull, FE, Kerr, LD. Differential serine phosphorylation regulates IkappaB-alpha inactivation. Biochem Biophys Res Commun, 257(3), 798-806, 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. PMCID:146529

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. PMCID:40538

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. PMCID:338354

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