Bridget S. Wilson, Ph.D.

Figure 1. Transmission electron micrograph of rat peritoneal mast cells. Note abundance of large, dense granules. These organelles are really "secretory lysosomes".


	Bridget S. Wilson, Ph.D. Professor, Department of Pathology Co-Director, Hematalogic Malignancies Program, UNM Cancer Center


	Contact information: Bridget S. Wilson, Ph.D. Cancer Research Facility, Room 205 University of New Mexico School of Medicine Albuquerque, New Mexico 87131 phone (505) 272-8852 fax (505) 272-1435 e-mail: bwilson@salud.unm.edu


	Figure 2. GFP - labeled mast cell granules move on cytoskeletal "tracks" VIDEO (requires QuickTime Player)


	Figure 3. Immunogold particles (10 nm) mark antigen-stimulated high affinity IgE receptors in signaling microdomain. Note receptors also enter coated pits in this domain.


	Figure 5. Click on the movie to see a simulation of calcium release through clustered IP3 receptors (S. Means)

				Figure 7. Click on this movie to see a 3D reconstruction demonstrating the close proximity of the endoplasmic reticulum with mitochondria (J. Zhang, based upon tomographic data acquired at the National Center for Microscopy and Imaging Reaserch (NCMIR) at UCSD) .
	Figure 6. Click on this movie to see a simulation of calcium release through diffuse IP3 receptors (S. Means)

The Wilson laboratory combines an interest in both membrane trafficking and signal transduction, in normal and disease cells.

Membrane Microdomains. We use an innovative electron microscopic approach to follow the reorganization of plasma membrane signaling components --- including receptors, tyrosine kinases, phosphopholipases and adaptor proteins --- that occurs after activation. The high spatial resolution provided by electron microscopy is complemented by live cell imaging approaches for temporal resolution, in collaboration with Dr. Diane Lidke, We primarily focus on these classes of receptors:

1.    Fc receptors, particularly the high affinity IgE receptor, FceRI of mast cells and basophils.    Various aspects of FceRI receptor behavior -- including localization in “Protein Islands”, confinement in cytoskeletal corrals and internalization mechanisms -- are the focus of NIAID-funded studies.    In addition, “crosstalk” between FceRI and other mast cell/basophil receptors is a major focus of the NIGMS-funded New Mexico Spatiotemporal Modeling Center (Oliver, PI).

2.    ErbB family of receptors, particularly in the context of breast and ovarian cancer (UNM clinical partner, Dr. Carolyn Muller). This work is aligned with the Interagency Modeling and Analysis Group initiative for multi-scale modeling. For information on this program, go to http://www.nibib.nih.gov/Research/MultiScaleModeling/IMAG.

3.    Receptors and accessory molecules involved in growth and survival of pre-B acute lymphoblastic leukemia (UNM clinical partner, Dr. Stuart Winter). This project is supported by a Leukemia/Lymphoma Society SCOR award to a consortium of UNM investigators (Wilman, PI; Wilson, Project PI).

Organization and Dynamics of Calcium Stores. We use a combination of high resolution microscopy and mathematical modeling to study calcium mobilization in the context of cell geometry. See the movies on this page for a demonstration of some modeling results.   Continuation of this project is funded through the NIGMS-funded New Mexico Spatiotemporal Modeling Center.

Publications (Partial list from over 70)

·         Wilson BS , Deanin GG, Standefer JE, VanderJagt D, Oliver JM. (1989) Depletion of guanine nucleotides with mycophenolic acid suppresses IgE-mediated degranulation in rat basophilic leukemia cells. J. Immunol. 143:259-265.

·         Wilson BS , Palade GE, Farquhar MG. (1993) ER-to-Golgi transport assay based on 0-glycosylation of native glycophorin in permeabilized erythroleukemia cells: Role for G_i3. PNAS USA 90:1681-1685.

·         Wilson BS , Komuro M, Farquhar MG. (1994) Cellular variations in heterotrimeric G-protein localization and expression in rat pituitary. Endocrinology 134:233-244.

·         Wilson BS , Meinkoth JL, McCaffery M, Nuoffer C, Feramisco JR, Balch WE, Farquhar MG. (1994) A Rab1 mutant affecting guanine nucleotide exchange promotes disassembly of the Golgi apparatus. J. Cell Biology 125:557-571.

·         Oliver JM, Burg DL, Wilson BS , McLaughlin JL and Geahlen RL. (1994) Inhibition of mast cell FceRI-mediated signaling and effector function by the Syk-selective inhibitor, piceatannol. J. Biol. Chem. 269:29697-29703.

·         Wilson BS , Kapp N, Lee RJ, Pfeiffer JR, Martinez AM, Platt Y, Letourneur F and Oliver JM. (1995) Distinct functions of the FceRI g and b subunits in the control of FceRI-mediated tyrosine kinase activation and signaling responses in RBL-2H3 mast cells. J. Biol. Chem. 270:4013-4022.

·         Barker S, Caldwell K, Hall A, Martinez AM, Pfeiffer JR, Oliver JM and Wilson BS. (1995) Wortmannin blocks lipid and protein kinase activities associated with PI 3-kinase and inhibits a specific subset of responses induced by FceRI crosslinking. Mol. Biol. Cell 6: 1145-1158.

·         Barker SA, Caldwell KK, Pfeiffer JR and Wilson BS. (1998) Wortmannin-sensitive phosphorylation, translocation and activation of PLCg1, but not PLCg2, in antigen-stimulated RBL-2H3 mast cells. Mol. Biol. Cell. 9: 483-496.

·         Wilson, BS , Pfeiffer JR, Smith AJ, Oliver, JM, Oberdorf, J, and Wojicikiewicz, RJH. (1998) Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors. Mol. Biol. Cell. 9: 1465-1478.

·         Kepley CL, Wilson BS and Oliver JM. (1998) Roles for the protein tyrosine kinases Lyn, Syk and Zap-70 in FceRI-mediated human basophil degranulation. J. Allergy Clin. Immunol. 102:304-310.

·         Graham TE, Pfeiffer JR, Lee RJ, Kusewitt DF, Martinez AM, Foutz T, Wilson BS and Oliver JM. (1998) MEK/ERK activation in ras-disabled RBL-2H3 mast cells and novel roles for geranylgeranylated and farneyslated proteins in FceR1-mediated signalling. J. Immunol. 161:6733-6744.

·         Ortega EM, Lara M, Lee, I, Santana C, Martinez AM, Pfeiffer JR, Lee RJ, WilsonBS and Oliver JM. (1999) Lyn dissociation from phosphorylated FceRI subunits: a new regulatory step in the FceR1 signaling cascade revealed by studies of FceR1 dimer signaling activity. J. Immunol. 162:176-185.

·         Kepley CL, Youssef L, Andrews RP, Wilson BS and Oliver JM. (1999) Syk deficiency in nonreleaser basophils. J. Allergy Clin. Immunol. 104:279-284.

·         Wilson BS , Pfeiffer JR and Oliver JM. (2000) Observing FceRI signalling from the inside of the mast cell membrane. J. Cell Biology 149:1131-1142.

·         Kepley CL, Cambier J, Lujan D, Ortega E, Morel PA, Wilson BS, Oliver JM. (2000) Negative regulation of FceRI : signaling by co-crosslinking to FceRII in basophils. J. Allergy Clin Immunol. 106: 337-348.

·         Oliver JM, Kepley CL, Ortega E and Wilson BS. (2000) Immunologically-mediated signaling in basophils and mast cells: finding therapeutic targets for allergic diseases in the human FceRI signaling pathway. Immunopharm. 48:269-281.

·         Kepley CL, Youssef L, Andrews RP, Wilson BS and Oliver JM. (2000) Turning off IgE-mediated signaling Nature’s way: reversible Syk deficiency in non-releaser basophils. Allergy Clinical Immunol. Intl. 12:11-17

·         Kepley CL, Youssef L, Andrews RP, Wilson BS , Oliver JM. (2000) Multiple defects in FceRI-mediated signaling in Syk-deficient nonreleaser basophils & IL-3-induced recovery of Syk expression & secretion. J. Immunol. 165:5913-5920.

·         Smith AJ, Surviladze Z, Gaudet EA, Backer JM, Mitchell CA, Wilson BS. (2001) p110b and p110d PI-3 kinases upregulate upregulate FceRI-activated Ca²⁺ influx by enhancing IP₃ production. J. Biol. Chem. 276:17213-17220

·         Wilson, BS. J.R. Pfeiffer, Z. Surviladze, E.A. Gaudet and J.M. Oliver. (2001) High resolution mapping reveals distinct FceRI and LAT domains in activated mast cells. J. Cell Biology 154:645-658.

·         Lara M, Ortega E, Pecht I, Pfeiffer JR, Martinez AM, Lee RJ, Surviladze Z, Wilson BS, Oliver JM. (2001) Overcoming the signaling defect of Lyn-sequestering, signal-curtailing FceRI dimers. J. Immunol. 167:4329-4337.

·         Wilson BS , Pfeiffer JR and Oliver JM. (2002) FceRI signaling observed from the inside of the mast cell membrane. Mol. Immunol. 38:1259-1268.

·         Smith AJ, Pfeiffer JR, Zhang J, Martinez AM, Griffiths GM and Wilson BS. (2003) Microtubule-dependent transport of secretory vesicles in RBL-2H3 cells. Traffic 4: 302-312.

·         Lam V, Kalesnikoff J, Lee CWK, Hernandez-Hansen V, Wilson BS, Oliver JM and Krystal G. (2003) IgE alone stimulates mast cell adhesion to fibronectin via pathways similar to those used by IgE + antigen but distinct from those used by Steel factor. Blood 102:1405-1413.

·         Wilson, BS , SL Steinberg, K Liederman, JR Pfeiffer, Z Surviladze, J Zhang, LE Samelson, LH Yang, PG Kotula and JM Oliver. (2004) Markers for detergent-resistant lipid rafts occupy distinct and dynamic domains in native membranes. Mol. Biol Cell 15: 2580-2592.

·         Hernandez-Hansen, V, AJ Smith, Z Surviladze, T Maizel, A Chigaev, J Kalesnikoff, CA Lowell, LA Sklar, G Krystal, BS Wilson and JM Oliver. (2004) Dysregulated FceRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells. J. Immunology 173: 100-112.

·         Valna P, Ledbduska P, Draberova L, Henegerg P, Boubelik M, V, Malissen M, Wilson BS, Horejsi V and Draber P. (2004) Negative regulatory role of the non-T cell activation linker in mast cell signaling. J. Exp. Medicine. 200:1001-1013

·         Kim J-H, L Cramer, H Mueller, BS Wilson and B. Vilen. (2005) Independent trafficking of Ig-a/b and mIg is facilitated by dissociation of the BCR complex. J. Immunology. 175: 147-154.

·         H ernandez-Hansen,V, JDJ Bard, JA Wilder, CA Lowell, BS Wilson and JM Oliver. (2005) Increased expression of genes linked to FceRI signaling and to chemokine and cytokine production in Lyn-deficient mast cells. J. Immunology. 175: 7880 - 7888.

·         Zhang, J, K Leiderman, JR Pfeiffer, BS Wilson, JM Oliver and SL Steinberg. (2006) Characterizing the topography of membrane receptors and signaling molecules from spatial patterns obtained using nanometer-scale electron –dense probes and electron microscopy. Micron 37:14-34.

·         D. J. Frankel, J. Pfeiffer, J. M. Oliver, BS Wilson and A. R. Burns. (2006) Revealing the topography of cellular membrane domains by combined Atomic Force Microscopy/fluorescence Imaging. Biophysical J. 90: 2404-2413 (Cover).

·         Mean, S, T Mazel, A Smith, J Shadid, J Shepard, RJH Wojicikiewicz, G. Smith and BS Wilson. (2006) Reaction diffusion modeling of calcium dynamics with realistic ER geometry. Biophysical J. 91:537-557.

·         BF Lillemeier, JR. Pfeiffer, Z Surviladze, BS Wilson and MM Davis. (2006) Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton.Proc. Natl. Acad. Sci. USA 103: 18992-18997.

·         M Xue, G Hsieh, M Raymond-Stintz, S Steinberg, E Prossnitz , JM Oliver, D Lidke and BS Wilson. (2007) FPR and FceRI occupy common domains for signaling and internalization. Mol. Biol. Cell 18:1410-1420.

·         LA Youssef, M Schuyler, L Gilmartin, G Pickett, C Tarleton, T Archibeque, C Qualles, BS Wilson and JM Oliver. (2007) “Non-releaser” and “cycler” basophils occur in both control and asthmatic subjects: distinct basal and FceRI-activated gene expression profiles in the non-releaser and releaser phenotypes. J. Immunology 178: 4584 - 4594.

·         Z Surviladze, HA Harrison, RC Murphy and BS Wilson. (2007) FceRI and Thy-1 domains have unique protein and lipid compositions. J. of Lipid Research. 48: 1325-1335

·         BS Wilson, JR Pfeiffer, M Raymond-Stintz, D Lidke, K Lidke, N Andrews and JM Oliver. (2007) Exploring membrane domains using native membrane sheets and transmission electron microscopy. Methods in Molecular Biology, Lipid Rafts. T. McIntosh, Ed. Humana Press 398:247-263.

·         S.Yang, M.A. Raymond-Stintz, W. Ying, J. Zhang, D.S. Lidke, S.L. Steinberg, L. Williams, J.M. Oliver, B.S. Wilson. (2007) Mapping ErbB receptors on breast cancer cell membranes during signal transduction. J. Cell Science 120: 2763-2773.

·         BA Stout, K. Melendez, JC Seagrave, MJ Holtzman, B. Wilson, J Xiang, Y Tesfagzi. (2007) STAT1 activation causes translocation of Bax to the ER during the resolution of airway mucous cell hyperplasia by IFN-g. J. Immunology 178:8107-8116.

·         L. Gilmartin, CA Tarleton, M Schuyler, BS Wilson and J.M. Oliver (2008) A Comparison of Inflammatory Mediators Released by Basophils of Asthmatic and Control Subjects in Response to High Affinity IgE Receptor Aggregation. Inter. Archives of Allergy & Immun. 145:182-192

·         J. Zhang, S.L. Steinberg, B.S. Wilson, J.M. Oliver, L. R. Williams. (2008) Markov Random Field modeling of the spatial distribution of proteins on cell membranes. Bulletin of Mathematical Biology 70:297-321

·         JI Kashiwakura, S Xiao, J Kitaura, Y Kawakami, M Maeda-Yamamoto, JR Pfeiffer, BS Wilson, U Blank and T Kawakami. (2008) IgE accelerates in vitro development of mast cells and modifies their phenotype. J. Leukocyte Biol. In press. (Cover)

·         T Russell, JM Oliver, BS Wilson, SS Winter and X Meng. (2008) Ikaros splice variants in monozygotic twins with MLL-rearranged precursor-B acute lymphoblastic leukemia. J. Pediatric Hem Onc 30:941-944.

·         NL Andrews, K Lidke, AR Burns, JM Oliver, BS Wilson and D Lidke. (2008) Actin restricts FceRI diffusion and facilitates antigen-induced receptor immobilization. Nature Cell Biology 10:955-963.

·         Hsieh, W Shu, S Yang, M Raymond-Stintz, D Vlahos, S Steinberg, BS Wilson* and J Edwards. (2008) Stochastic simulations of ErbB homo and hetero-dimerization: potential impacts of receptor conformational state and spatial segregation. IET Systems Biology 2(5): 256-272.             * corresponding author

·         T Mazel, R Raymond, M Raymond-Stinz, S Jett and BS Wilson. (2009) Stochastic modeling of calcium in 3D geometry. Biophysical Journal 96:1691-1706.

·         MN Costa, K Radhakrishnan, BS Wilson, DG Vlachos and JS Edwards. (2009) Coupled stochastic spatial and non-spatial simulations of ErbB1 signaling pathways demonstrate the importance of spatial organization in signal transduction. PLoS One, in press.

·         L Andrews, JR Pfeiffer, AM Martinez, DM Haaland, RW Davis, T Kawakami, JM Oliver, BS Wilson, DS Lidke. Small, mobile FceRI aggregates are signaling competent. Immunity, in press.

·         M Oliver, CA Tarleton, L Gilmartin, T Archigeque, CR Qualls, L Diehl, BS Wilson, M Schuyler. (2009) Reduced FceRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during Omalizumab therapy. Internat. Archives Allergy Immunology, in press.