21 results on '"Gehlhausen, Jeffrey R"'
Search Results
2. Cognitive bias in the patient encounter: Part I. Background and significance
- Author
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Ko, Christine J., Gehlhausen, Jeffrey R., Cohen, Jeffrey M., and Croskerry, Pat
- Published
- 2025
- Full Text
- View/download PDF
3. Rituximab
- Author
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Gehlhausen, Jeffrey R., primary, Heffernan, Michael P., additional, and Tomayko, Mary M., additional
- Published
- 2021
- Full Text
- View/download PDF
4. Contributors
- Author
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Adams, David R., primary, Adams, Stewart, additional, Amin, Mina, additional, Avashia-Khemka, Nidhi, additional, Beck, Kristen M., additional, Bhatia, Bhavnit K., additional, Bhatia, Sravya Mallam, additional, Bhutani, Tina, additional, Braue, Jonathan A., additional, Brodell, Robert T., additional, Brodland, David G., additional, Broussard-Steinberg, Candace, additional, Callen, Jeffrey P., additional, Camisa, Charles, additional, Chehade, Ahmad, additional, Chima, Margot, additional, Clark, Richard A., additional, Cline, Abigail, additional, Cordoro, Kelly M., additional, Cruz Ramón, Julio C., additional, Davis, Loretta S., additional, Feld, Salma de la, additional, M.C. DeKlotz, Cynthia, additional, Duprat, Gabrielle-Eugenie, additional, Eaglstein, William H., additional, Elston, Carly A., additional, Elston, Dirk M., additional, Emerson, Ashley N., additional, Fabbro, Stephanie K., additional, Feldman, Steven R., additional, Ferris, Laura K., additional, Foley, Kelly A., additional, Forman, Seth B., additional, Garofola, Craig, additional, Gehlhausen, Jeffrey R., additional, Gelfand, Joel M., additional, Girardi, Michael, additional, Goerge, Tobias, additional, Gordon, Kenneth B., additional, Greiling, Teri M., additional, Grinich, Erin E., additional, Grove, Daniel, additional, Gupta, Aditya K., additional, Haggstrom, Anita, additional, Haley, Christopher T., additional, Hall, Russell P., additional, Hamzavi, Iltefat, additional, Heffernan, Michael P., additional, Helfrich, Yolanda R., additional, Hessel, Adam B., additional, Higgins, Shauna, additional, High, Whitney A., additional, Hrynewycz, Katherine, additional, Hsu, Sylvia, additional, Huether, Michael J., additional, Isaacs, Michael J., additional, Kaminer, Michael S., additional, Kandula, Prasanthi, additional, Kandula, Swetha, additional, Kang, Sewon, additional, Kapp, Marshall B., additional, Kim, Hee Jin, additional, Kim, Sa Rang, additional, Kingsley, Melanie, additional, Knowles, Sandra R., additional, Koo, John Y.M., additional, Kulp-Shorten, Carol L., additional, Landis, Megan N., additional, Lebwohl, Mark G., additional, Lee, Erica B., additional, Lee, Katherine B., additional, Lewis, Amy B., additional, Lim, Geoffrey F.S., additional, Lim, Henry W., additional, Lockshin, Benjamin N., additional, Luger, Thomas A., additional, Majerowski, Jacquelyn, additional, Mark, Lawrence A., additional, Marshall, Dana, additional, Martell, David, additional, Mays, Rachel R., additional, McElhiney, Linda F., additional, Mirowski, Ginat W., additional, Mori, Shoko, additional, Motaparthi, Kiran, additional, Mui, Uyen Ngoc, additional, Murray, Christian, additional, Nielson, Colton, additional, Noe, Megan H., additional, Okoye, Ginette A., additional, Owen, Cindy England, additional, Patton, Timothy, additional, Piette, Warren W., additional, Rahnama-Moghadam, Sahand, additional, Ramachandran, Sarika Manoj, additional, Rancour, Elizabeth A., additional, Rao, Jaggi, additional, Rosenbach, Misha, additional, Roy, Katherine, additional, Sachs, Dana L., additional, Sami, Naveed, additional, Sawaya, Marty E., additional, Schadt, Courtney R., additional, Schaffenburg, William, additional, Schlosser, Bethanee J., additional, Sekhon, Sahil, additional, Shah, Vidhi V., additional, Shapiro, Lori E., additional, Shear, Neil H., additional, Sheehan, Michael, additional, Simpson, Eric L., additional, Snodgrass, Alexandra, additional, Solish, Nowell, additional, Somani, Ally-Khan, additional, Somani, Najwa, additional, Strober, Bruce, additional, Sulk, Mathias, additional, Suozzi, Kathleen C., additional, Tharp, Michael D., additional, Tomayko, Mary M., additional, Tyring, Stephen K., additional, Vogt-Schiavo, Kaitlin, additional, Vuppalanchi, Raj, additional, Wang, Steve Q., additional, Weston, Gillian, additional, Wolverton, Stephen E., additional, Wu, Jashin J., additional, Wysong, Ashley, additional, Zic, John, additional, and Zwerner, Jeffrey P., additional
- Published
- 2021
- Full Text
- View/download PDF
5. 40 - Autoantibodies Encountered in Patients with Autoimmune Connective Tissue Diseases
- Author
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Gehlhausen, Jeffrey R., Jacobe, Heidi T., Sontheimer, Richard D., and Ramachandran, Sarika
- Published
- 2025
- Full Text
- View/download PDF
6. A case of eosinophilic dermatosis of hematologic malignancy with tissue-based Th2 cytokine profiling
- Author
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Xu, Suzanne, primary, Singh, Katelyn, additional, McNiff, Jennifer, additional, Damsky, William, additional, and Gehlhausen, Jeffrey R., additional
- Published
- 2022
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7. The importance of nerve microenvironment for schwannoma development
- Author
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Schulz, Alexander, Büttner, Robert, Hagel, Christian, Baader, Stephan L., Kluwe, Lan, Salamon, Johannes, Mautner, Victor-Felix, Mindos, Thomas, Parkinson, David B., Gehlhausen, Jeffrey R., Clapp, D. Wade, and Morrison, Helen
- Published
- 2016
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8. 30 - Rituximab
- Author
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Gehlhausen, Jeffrey R., Heffernan, Michael P., and Tomayko, Mary M.
- Published
- 2021
- Full Text
- View/download PDF
9. Normal hematopoiesis and neurofibromin-deficient myeloproliferative disease require Erk
- Author
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Staser, Karl, Park, Su-Jung, Rhodes, Steven D., Zeng, Yi, He, Yong Zheng, Shew, Matthew A., Gehlhausen, Jeffrey R., Cerabona, Donna, Menon, Keshav, Chen, Shi, Sun, Zejin, Yuan, Jin, Ingram, David A., Nalepa, Grzegorz, Yang, eng-Chun, and Clapp, D. Wade
- Subjects
Hematopoiesis -- Physiological aspects -- Research ,Myeloproliferative disorders -- Complications and side effects -- Prevention -- Risk factors -- Research -- Genetic aspects ,Protein kinases -- Genetic aspects -- Research -- Physiological aspects ,Health care industry - Abstract
Neurofibromatosis type 1 (NF1) predisposes individuals to the development of juvenile myelomonocytic leukemia (JMML), a fatal myeloproliferative disease (MPD). In genetically engineered murine models, nullizygosity of Nf1, a tumor suppressor [...]
- Published
- 2013
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10. A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation
- Author
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Gehlhausen, Jeffrey R., Park, Su-Jung, Hickox, Ann E., Shew, Matthew, Staser, Karl, Rhodes, Steven D., Menon, Keshav, Lajiness, Jacquelyn D., Mwanthi, Muithi, Yang, Xianlin, Yuan, Jin, Territo, Paul, Hutchins, Gary, Nalepa, Grzegorz, Yang, Feng-Chun, Conway, Simon J., Heinz, Michael G., Stemmer-Rachamimov, Anat, Yates, Charles W., and Wade Clapp, D.
- Published
- 2015
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11. Contributors
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Abdallah, M. Abdel Rahim, Abdallah, Mahmoud M.A., Abdallah, Marwa, Adler, Brandon L., Adusumilli, Nagasai C., Akaike, Tomoko, Alavi, Afsaneh, Amagai, Masayuki, Ambros-Rudolph, Priv.-Doz. Dr. Christina M., Rox Anderson, R., Antaya, Richard J., Ardigò, Marco, Argenyi, Zsolt B., Argenziano, Giuseppe, Avram, Marc R., Avram, Mathew M., Baker, Christopher, Barete, Stéphane, Barnhill, Raymond L., Baselga, Eulalia, Baugh, Erica G., Bayliss, Susan J., Beck, Lisa A., Bergqvist, Christina, Bernhard, Jeffrey D., Blanton, Lucas S., Bodemer, Apple, Bolognia, Jean L., Borradori, Luca, Dominik Braun, Andreas, Bravo, Francisco G., Brodland, David G., Brownell, Isaac, Bruckner, Anna L., Bruckner-Tuderman, Leena, Burkhart, Craig G., Burkhart, Craig N., Burrows, Nigel P., Callen, Jeffrey P., Camacho, Francisco M., Cameli Carley, Alexandra, Carruthers, Alastair, Carruthers, Jean, Cartee, Todd V., Cerroni, Lorenzo, Chan, Roy K.W., Wu Chang, Mary, Chio, Martin T.W., Chosidow, Olivier, Christiano, Angela M., Clayton, Anna S., Cockerell MD MBA JD, Clay J., Cohen, Bernard A., Cohen, David E., Coleman, Kyle M., Coleman, William P., Kari Connolly, M., Cooper, Susan M., Corey, Kristen, Cowen, Edward W., Cribier, Bernard, Darling, Thomas N., Davis, Mark D.P., de Berker, David, De Leo, Vincent A., Detmar, Michael, Diana Draelos, Zoe, Duncan, Karynne O., Elewski, Boni E., Elias, Peter M., Elston, Dirk M., Eming, Sabine A., España, Agustín, Fairley, Janet A., Feingold, Kenneth R., Fine, Jo-David, Flowers, Franklin P., Fox, Matthew, Fraitag, Sylvie, Franceschini, Chiara, Frank, Jorge, French, Lars E., Fried, Isabella, Frieden, Ilona J., Garzon, Maria C., Gasslitter, Irina, Gattorno, Marco, Gehlhausen, Jeffrey R., Ghoreschi, Kamran, Goldman, Mitchel P., Goldsmith, Charya B., Gollnick, Harald P., Grattan, Clive E.H., Groves, Richard W., Guillén-Navarro, Encarna, Haemel, Anna K., Hafner, Ariela, Haggstrom, Anita N., Hand, Jennifer L., Hannam, Sarah, Hausauer, Amelia K., Hay, Roderick J., Helfrich, Yolanda R., Hernández-Martín, Ángela, Hertl, Michael, Heymann, Warren R., High, Whitney A., Hirakawa, Satoshi, Hivnor, Chad M., Hohl, Prof. Dr. med. Daniel M., Hönigsmann, Herbert, Hötzenecker, Wolfram, Howard, Josie, Howard, Renee M., Hruza, George J., Hrynewycz, Katherine, Hsiao, Jennifer L., Huang, Jennifer T., Hughey, Lauren C., Hull, Christopher M., Marchiony Hunt, Katherine, Ingen-Housz-Oro, Saskia, Irvine, Alan D., Iversen, Lars, Mark Jackson, J., Jackson, Scott M., Jacobe, Heidi T., Jebain, Joseph, Jessri, Maryam, Jones, Derek H., Jorizzo, Joseph L., Kaddu, Steven, Kalia, Sunil, Kang, Sewon, Kelly, Kristen M., Kelly, Robert, Kempf, Werner, Kim, Brian, Kirnbauer, Reinhard, Kirsner, Robert S., Kittler, Nicole W., Knowles BSc Phm, Sandra R., Ko, Christine J., Kocatürk, Emek, Koch, Priv.-Doz. Dr. Lukas, Koch, Peter J., Koh, Hong Yi, Koo, John Y.M., Koss, Tamara, Koster, Maranke I., Kroshinsky, Daniela, G. Kumar, Monique, Kutzner, Heinz H., Kwong, Bernice Y., Lalor, Leah E.B., Lam, Charlene, Latheef, Faheem, Lee, Lela A., Lenormand, Cédric, Lenz, Petra, Lesher, Jack L., Jr., Leslie, Kieron S., Lev-Tov, Hadar, Liegl-Atzwanger, Bernadette, Lim, Henry W., Hua Liang Lim, Joel, Linos, Eleni, Lio, Peter, Lipsker, Dan, Loomis, Cynthia A., Lui, Harvey, Luo, Su, Maari, Catherine, Machan, Salma, Madigan, Lauren M., Maguiness, Sheilagh M., Maiberger, Mary P., Mancini, Anthony J., Marchitto, Mark, Marks Jr, James G., Martínez-Menchón, Teresa, Mascaró, José M., Jr., Trent Massengale, William, Massone, Cesare, Mauro, Theodora M., Mc Aleer, Maeve A., Mc Calmont, Timothy H., Carol Mc Connell, R., Mc Govern, Thomas W., Matthew Mc Larney, R., Mc Meniman, Erin K., Mc Murray, Stacy L., Mc Namara, Kristin K., Mc Niff, Jennifer M., Mellerio, Jemima E., Menon, Gopinathan K., Metze, Dieter, Meyer, Jason, Micheletti, Robert G., Milam, Emily C., Millard-Garcia, Ashley N., Miller, Jami L., Mizukawa, Yoshiko, Molho-Pessach, Vered, Molina-Ruiz, Ana María, Monheit, Gary D., Morrell, Dean S., Mowad, Christen M., Mahindra Nayyar, Priya, Nelson, Amanda M., Nghiem, Paul, Ní Raghallaigh, Síona, Nixon AM, Rosemary L., Noguera-Morel, Lucero, North, Paula E., Nunley, Julia R., Nyström, Alexander, Teresa Ochoa, Maria, Oji, Vinzenz, Olbricht, Suzanne, Orlow, Seth J., Ortega-Loayza, Alex G., Ortonne, Jean-Paul, Oschmann, Anna, Paller, Amy S., Pasquali, Paola, Passeron, Thierry, Patterson, James W., P. Pereira, Manuel, Pfisterer, Karin, Piette, Warren W., Pincus, Laura B., Maria Piraccini, Bianca, Pittelkow, Mark R., Plewig, Gerd, Pollack, Sheldon V., Powell, Julie, Prausnitz, Mark R., Quist, Jennifer E., Quist, Sven R., Qureshi, Abrar A., Raimer, Ben G., Raimer, Sharon S., Raimer-Goodman, Lauren, Ramachandran, Sarika, Ramos-e-Silva, Marcia, Rapini, Ronald P., Ratner, Désirée, Reboli, Annette C., Reider, Norbert, Reizner, George T., Requena, Celia, Requena, Luis, Reynolds, Rachel, Cristina Ribeiro de Castro, Maria, Rich, Phoebe, Richard, Gabriele, Richards, Shawn W., Richert, Bertrand, Ringpfeil, Franziska, Röcken, Martin, Rogers MD FAAD, Nicole E., Rohrer, Thomas E., Rongioletti, Franco, Rosen, Cheryl F., Rosenbach, Misha A., Rudnicka, Lidia, Rünger, Thomas M., Saggini, Andrea, Saini, Sarbjit S., Sakamoto, Fernanda H., Saurat, Jean-Hilaire, Schadt, Courtney R., Ann Mc Leish, Stephanie, Schaffer, Julie V., Schaller, Martin, Schmuth, Matthias, Schwarz, Thomas, Schwarzenberger, Kathryn, Seneschal, Julien, Shani-Adir, Ayelet, Shapiro, Lori E., Shear, Neil H., Shi, Vivian Y., Shields, Bridget E., Shiohara, Tetsuo, Sidbury, Robert, Siller, Alfredo, Jr., Sivamani, Raja, Smith, Gideon P., Smith, Michael L., Smoller, Bruce R., Sommer, Lacy L., Sontheimer, Richard D., Sorg, Olivier, Peter Soyer, H., Sprecher, Eli, Ständer, Sonja, Stary, Angelika, Stary, Georg, Steadmon, Matthew, Stefanato, Catherine M., Seabury Stone, Mary, Stratman, Erik J., Süßmuth, Kira, Swetter, Susan M., Sybert, Virginia P., Hoon Tan, Suat, Tanzi, Elizabeth, Liang Tey, Hong, Tharp, Michael D., Tomasini, Carlo F., Torrelo, Antonio, Tosti, Antonella, Travelute, Christie R., Treister, Nathaniel, Trindade de Almeida, Ada Regina, Tsao, Hensin, Tschandl, Philipp, Tüting, Thomas, Tyring, Stephen K., Uitto, Jouni, van de Kerkhof, Peter C.M., Vandergriff, Travis W., Veness, Michael J., Verhave, Brendon, Vidimos, Allison T., Virós, Amaya, Ann Vleugels, Ruth, Walker, David H., Wanat, Karolyn A., Wang, Etienne C.E., Wang, Jennifer Y., Watsky, Kalman L., Weber, Benedikt, Weiss, Robert A., Weisshaar, Elke, Weninger, Wolfgang, Werth, Victoria P., Wesley, Naissan O., Weston, Gillian K., Whittaker, Sean, Wiesner, Thomas, Mark Wilkinson, S., Willemze, Rein, Winfield, Harry L., Wolf, Ingrid H., Wolf, Peter, Wolverton, Stephen E., Wood, Gary S., Yancey, Kim B., Yang, Eric J., Yang, Yul W., Yosipovitch, Gil, Rasar Young, Melissa, Zaba, Lisa C., Zachary, Christopher B., Zaenglein, Andrea L., Zalaudek, Iris, and Zone, John J.
- Published
- 2025
- Full Text
- View/download PDF
12. VEXAS Syndrome: Histiocytoid Cells With Feathery Cytoplasm as a Clue to the Diagnosis.
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Ko, Christine J., Odell, Ian, Gehlhausen, Jeffrey R., Leventhal, Jonathan, McNiff, Jennifer M., and Zubek, Amanda
- Subjects
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SWEET'S syndrome , *CYTOPLASM , *DIAGNOSIS , *SYNDROMES , *ENZYMES - Abstract
ABSTRACT VEXAS (
V acuoles,E 1‐ubiquitin activating enzyme UBA1 variant,X ‐linked,A utoinflammatory,S omatic) syndrome was initially described as having mature neutrophil‐predominant infiltrates. More recent reports suggest that infiltrates can be composed of variable cell types. We report three cases of VEXAS syndrome with seven total biopsies having in common histiocytoid cells with feathery cytoplasm; these cells may be a potential clue to the diagnosis. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
13. Ketotifen Modulates Mast Cell Chemotaxis to Kit-Ligand, but Does Not Impact Mast Cell Numbers, Degranulation, or Tumor Behavior in Neurofibromas of Nf1-Deficient Mice
- Author
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Burks, Ciersten A., primary, Rhodes, Steven D., additional, Bessler, Waylan K., additional, Chen, Shi, additional, Smith, Abbi, additional, Gehlhausen, Jeffrey R., additional, Hawley, Eric T., additional, Jiang, Li, additional, Li, Xiaohong, additional, Yuan, Jin, additional, Lu, Qingbo, additional, Jacobsen, Max, additional, Sandusky, George E., additional, Jones, David R., additional, Clapp, D. Wade, additional, and Blakeley, Jaishri O., additional
- Published
- 2019
- Full Text
- View/download PDF
14. Toxoplasmosis: The Heart of the Diagnosis
- Author
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England, James H, primary, Bailin, Samuel S, additional, Gehlhausen, Jeffrey R, additional, and Rubin, Donald H, additional
- Published
- 2018
- Full Text
- View/download PDF
15. A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas
- Author
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Gehlhausen, Jeffrey R, primary, Hawley, Eric, additional, Wahle, Benjamin Mark, additional, He, Yongzheng, additional, Edwards, Donna, additional, Rhodes, Steven D, additional, Lajiness, Jacquelyn D, additional, Staser, Karl, additional, Chen, Shi, additional, Yang, Xianlin, additional, Yuan, Jin, additional, Li, Xiaohong, additional, Jiang, Li, additional, Smith, Abbi, additional, Bessler, Waylan, additional, Sandusky, George, additional, Stemmer-Rachamimov, Anat, additional, Stuhlmiller, Timothy J, additional, Angus, Steven P, additional, Johnson, Gary L, additional, Nalepa, Grzegorz, additional, Yates, Charles W, additional, Wade Clapp, D, additional, and Park, Su-Jung, additional
- Published
- 2018
- Full Text
- View/download PDF
16. Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2
- Author
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Wahle, Benjamin M., primary, Hawley, Eric T., additional, He, Yongzheng, additional, Smith, Abbi E., additional, Yuan, Jin, additional, Masters, Andi R., additional, Jones, David R., additional, Gehlhausen, Jeffrey R., additional, Park, Su-Jung, additional, Conway, Simon J., additional, Clapp, D. Wade, additional, and Yates, Charles W., additional
- Published
- 2017
- Full Text
- View/download PDF
17. proteasome-resistant fragment of NIK mediates oncogenic NF- κ B signaling in schwannomas.
- Author
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Gehlhausen, Jeffrey R, Hawley, Eric, Wahle, Benjamin Mark, He, Yongzheng, Edwards, Donna, Rhodes, Steven D, Lajiness, Jacquelyn D, Staser, Karl, Chen, Shi, Yang, Xianlin, Yuan, Jin, Li, Xiaohong, Jiang, Li, Smith, Abbi, Bessler, Waylan, Sandusky, George, Stemmer-Rachamimov, Anat, Stuhlmiller, Timothy J, Angus, Steven P, and Johnson, Gary L
- Published
- 2019
- Full Text
- View/download PDF
18. A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation
- Author
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Gehlhausen, Jeffrey R., primary, Park, Su-Jung, additional, Hickox, Ann E., additional, Shew, Matthew, additional, Staser, Karl, additional, Rhodes, Steven D., additional, Menon, Keshav, additional, Lajiness, Jacquelyn D., additional, Mwanthi, Muithi, additional, Yang, Xianlin, additional, Yuan, Jin, additional, Territo, Paul, additional, Hutchins, Gary, additional, Nalepa, Grzegorz, additional, Yang, Feng-Chun, additional, Conway, Simon J., additional, Heinz, Michael G., additional, Stemmer-Rachamimov, Anat, additional, Yates, Charles W., additional, and Wade Clapp, D., additional
- Published
- 2014
- Full Text
- View/download PDF
19. Normal hematopoiesis and neurofibromin-deficient myeloproliferative disease require Erk
- Author
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Staser, Karl, primary, Park, Su-Jung, additional, Rhodes, Steven D., additional, Zeng, Yi, additional, He, Yong Zheng, additional, Shew, Matthew A., additional, Gehlhausen, Jeffrey R., additional, Cerabona, Donna, additional, Menon, Keshav, additional, Chen, Shi, additional, Sun, Zejin, additional, Yuan, Jin, additional, Ingram, David A., additional, Nalepa, Grzegorz, additional, Yang, Feng-Chun, additional, and Clapp, D. Wade, additional
- Published
- 2012
- Full Text
- View/download PDF
20. Toxoplasmosis: The Heart of the Diagnosis.
- Author
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England, James H, Bailin, Samuel S, Gehlhausen, Jeffrey R, and Rubin, Donald H
- Abstract
Toxoplasma gondii is a common parasite that infects warm-blooded animals, including humans, and is a foodborne pathogen. We report a case of acute toxoplasmosis in a 76-year-old man after ingestion of the undercooked heart of a white-tailed deer (Odocoileus virginianus) in Tennessee. The patient's adult grandson, who also consumed part of the heart, became ill with nearly identical symptoms, though he did not seek medical care. This case highlights important public health concerns about deer-to-human transmission of Toxoplasma. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
21. A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas.
- Author
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Gehlhausen JR, Hawley E, Wahle BM, He Y, Edwards D, Rhodes SD, Lajiness JD, Staser K, Chen S, Yang X, Yuan J, Li X, Jiang L, Smith A, Bessler W, Sandusky G, Stemmer-Rachamimov A, Stuhlmiller TJ, Angus SP, Johnson GL, Nalepa G, Yates CW, Wade Clapp D, and Park SJ
- Subjects
- Animals, Autocrine Communication genetics, Carcinogenesis genetics, Caspase 1 genetics, Cell Proliferation genetics, Disease Models, Animal, Gene Expression Regulation, Neoplastic, Hepatocyte Growth Factor genetics, Humans, Mice, Molecular Targeted Therapy, NF-kappa B genetics, Neurilemmoma complications, Neurilemmoma drug therapy, Neurilemmoma pathology, Neurofibromatosis 2 complications, Neurofibromatosis 2 drug therapy, Neurofibromatosis 2 pathology, Proteasome Endopeptidase Complex genetics, Proto-Oncogene Mas, Proto-Oncogene Proteins c-met genetics, Schwann Cells, Signal Transduction genetics, NF-kappaB-Inducing Kinase, Neurilemmoma genetics, Neurofibromatosis 2 genetics, Neurofibromin 2 genetics, Protein Serine-Threonine Kinases genetics
- Abstract
Schwannomas are common, highly morbid and medically untreatable tumors that can arise in patients with germ line as well as somatic mutations in neurofibromatosis type 2 (NF2). These mutations most commonly result in the loss of function of the NF2-encoded protein, Merlin. Little is known about how Merlin functions endogenously as a tumor suppressor and how its loss leads to oncogenic transformation in Schwann cells (SCs). Here, we identify nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-inducing kinase (NIK) as a potential drug target driving NF-κB signaling and Merlin-deficient schwannoma genesis. Using a genomic approach to profile aberrant tumor signaling pathways, we describe multiple upregulated NF-κB signaling elements in human and murine schwannomas, leading us to identify a caspase-cleaved, proteasome-resistant NIK kinase domain fragment that amplifies pathogenic NF-κB signaling. Lentiviral-mediated transduction of this NIK fragment into normal SCs promotes proliferation, survival, and adhesion while inducing schwannoma formation in a novel in vivo orthotopic transplant model. Furthermore, we describe an NF-κB-potentiated hepatocyte growth factor (HGF) to MET proto-oncogene receptor tyrosine kinase (c-Met) autocrine feed-forward loop promoting SC proliferation. These innovative studies identify a novel signaling axis underlying schwannoma formation, revealing new and potentially druggable schwannoma vulnerabilities with future therapeutic potential.
- Published
- 2019
- Full Text
- View/download PDF
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