Affiliations

Director, Shared Resources, Jonsson Comprehensive Cancer Center, Immunity, Inflammation, Infection, & Transplantation (I3T) Research Initiative

Associate Professor, Microbiology, Immunology, Molecular Genetics, Molecular & Medical Pharmacology

Member, Cell & Developmental Biology GPB Home Area, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, JCCC Signal Transduction and Therapeutics Program Area, Molecular Pharmacology GPB Home Area, themes

The Bensinger laboratory is focused on understanding how lipid metabolism influences the growth, survival and function of rapidly dividing normal and neoplastic cells. His laboratory recently revealed a lipid metabolic checkpoint that regulates cell cycle progression, cellular growth and viability in lymphocytes. Key ongoing studies include elucidating the signal transduction and regulatory networks that link growth receptor signaling to lipid anabolic programs in the adaptive immune system. We are also interested in understanding how lipid signals influence adaptive immune responses and self-tolerance. Current studies in the laboratory have found that dysregulation of lipid metabolism intrinsically influences adaptive immune cell function and autoimmune pathogenesis. Other important studies in the laboratory are focused on determining if lipid metabolic programs contribute to carcinogenesis, tumor growth and pathogenesis. Finally, we continue to seek out how to target key aspects of lipid metabolism to decrease tumor growth and alter immune cell function.

Gholkar Ankur A, Cheung Keith, Williams Kevin J, Lo Yu-Chen, Hamideh Shadia A, Nnebe Chelsea, Khuu Cindy, Bensinger Steven J, Torres Jorge Z Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division. The Journal of biological chemistry. 2016; 291(33): 17001-8. Kidani Yoko, Bensinger Steven J Modulating Cholesterol Homeostasis to Build a Better T Cell. Cell metabolism. 2016; 23(6): 963-4. Ribas Vicent, Drew Brian G, Zhou Zhenqi, Phun Jennifer, Kalajian Nareg Y, Soleymani Teo, Daraei Pedram, Widjaja Kevin, Wanagat Jonathan, de Aguiar Vallim Thomas Q, Fluitt Amy H, Bensinger Steven, Le Thuc, Radu Caius, Whitelegge Julian P, Beaven Simon W, Tontonoz Peter, Lusis Aldons J, Parks Brian W, Vergnes Laurent, Reue Karen, Singh Harpreet, Bopassa Jean C, Toro Ligia, Stefani Enrico, Watt Matthew J, Schenk Simon, Akerstrom Thorbjorn, Kelly Meghan, Pedersen Bente K, Hewitt Sylvia C, Korach Kenneth S, Hevener Andrea L Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Science translational medicine. 2016; 8(334): 334ra54. Meriwether David, Sulaiman Dawoud, Wagner Alan, Grijalva Victor, Kaji Izumi, Williams Kevin J, Yu Liqing, Fogelman Spencer, Volpe Carmen, Bensinger Steven J, Anantharamaiah G M, Shechter Ishaiahu, Fogelman Alan M, Reddy Srinivasa T Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux. Journal of lipid research. 2016; 57(7): 1175-93. Cunningham Cameron R, Champhekar Ameya, Tullius Michael V, Dillon Barbara Jane, Zhen Anjie, de la Fuente Justin Rafael, Herskovitz Jonathan, Elsaesser Heidi, Snell Laura M, Wilson Elizabeth B, de la Torre Juan Carlos, Kitchen Scott G, Horwitz Marcus A, Bensinger Steven J, Smale Stephen T, Brooks David G Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence. PLoS pathogens. 2016; 12(1): e1005356. York Autumn G, Williams Kevin J, Argus Joseph P, Zhou Quan D, Brar Gurpreet, Vergnes Laurent, Gray Elizabeth E, Zhen Anjie, Wu Nicholas C, Yamada Douglas H, Cunningham Cameron R, Tarling Elizabeth J, Wilks Moses Q, Casero David, Gray David H, Yu Amy K, Wang Eric S, Brooks David G, Sun Ren, Kitchen Scott G, Wu Ting-Ting, Reue Karen, Stetson Daniel B, Bensinger Steven J Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell. 2015; 163(7): 1716-29. Mercer Jacob L, Argus Joseph P, Crabtree Donna M, Keenan Melissa M, Wilks Moses Q, Chi Jen-Tsan Ashley, Bensinger Steven J, Lavau Catherine P, Wechsler Daniel S Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis. PloS one. 2015; 10(6): e0129776. Xie Letian X, Williams Kevin J, He Cuiwen H, Weng Emily, Khong San, Rose Tristan E, Kwon Ohyun, Bensinger Steven J, Marbois Beth N, Clarke Catherine F Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis. Journal of lipid research. 2015; 56(4): 909-19. Kidani Yoko, Bensinger Steven J Lipids rule: resetting lipid metabolism restores T cell function in systemic lupus erythematosus. The Journal of clinical investigation. 2014; 124(2): 482-5. Williams Kevin J, Argus Joseph P, Zhu Yue, Wilks Moses Q, Marbois Beth N, York Autumn G, Kidani Yoko, Pourzia Alexandra L, Akhavan David, Lisiero Dominique N, Komisopoulou Evangelia, Henkin Amy H, Soto Horacio, Chamberlain Brian T, Vergnes Laurent, Jung Michael E, Torres Jorge Z, Liau Linda M, Christofk Heather R, Prins Robert M, Mischel Paul S, Reue Karen, Graeber Thomas G, Bensinger Steven J An essential requirement for the SCAP/SREBP signaling axis to protect cancer cells from lipotoxicity. Cancer research. 2013; 73(9): 2850-62. Akhavan David, Pourzia Alexandra L, Nourian Alex A, Williams Kevin J, Nathanson David, Babic Ivan, Villa Genaro R, Tanaka Kazuhiro, Nael Ali, Yang Huijun, Dang Julie, Vinters Harry V, Yong William H, Flagg Mitchell, Tamanoi Fuyuhiko, Sasayama Takashi, James C David, Kornblum Harley I, Cloughesy Tim F, Cavenee Webster K, Bensinger Steven J, Mischel Paul S De-repression of PDGFRβ transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients. Cancer discovery. 2013; 3(5): 534-47. Ahler Ethan, Sullivan William J, Cass Ashley, Braas Daniel, York Autumn G, Bensinger Steven J, Graeber Thomas G, Christofk Heather R Doxycycline alters metabolism and proliferation of human cell lines. PloS one. 2013; 8(5): e64561. Argus Joseph P, Bensinger Steven J Immunology. Fueling function over expansion in T cells. Science (New York, N.Y.). 2013; 341(6141): 37-8. Schjerven Hilde, McLaughlin Jami, Arenzana Teresita L, Frietze Seth, Cheng Donghui, Wadsworth Sarah E, Lawson Gregory W, Bensinger Steven J, Farnham Peggy J, Witte Owen N, Smale Stephen T Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros. Nature immunology. 2013; 14(10): 1073-83. Kidani Yoko, Elsaesser Heidi, Hock M Benjamin, Vergnes Laurent, Williams Kevin J, Argus Joseph P, Marbois Beth N, Komisopoulou Evangelia, Wilson Elizabeth B, Osborne Timothy F, Graeber Thomas G, Reue Karen, Brooks David G, Bensinger Steven J Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nature immunology. 2013; 14(5): 489-99. York Autumn G, Bensinger Steven J Subverting sterols: rerouting an oxysterol-signaling pathway to promote tumor growth. The Journal of experimental medicine. 2013; 210(9): 1653-6. Hong Cynthia, Kidani Yoko, A-Gonzalez Noelia, Phung Tram, Ito Ayaka, Rong Xin, Ericson Katrin, Mikkola Hanna, Beaven Simon W, Miller Lloyd S, Shao Wen-Hai, Cohen Philip L, Castrillo Antonio, Tontonoz Peter, Bensinger Steven J Coordinate regulation of neutrophil homeostasis by liver X receptors in mice. The Journal of clinical investigation. 2012; 122(1): 337-47. Wilson Elizabeth B, Kidani Yoko, Elsaesser Heidi, Barnard Jennifer, Raff Laura, Karp Christopher L, Bensinger Steven, Brooks David G Emergence of distinct multiarmed immunoregulatory antigen-presenting cells during persistent viral infection. Cell host & microbe. 2012; 11(5): 481-91. Kidani Yoko, Bensinger Steven J Liver X receptor and peroxisome proliferator-activated receptor as integrators of lipid homeostasis and immunity. Immunological reviews. 2012; 249(1): 72-83. Bensinger Steven J, Christofk Heather R New aspects of the Warburg effect in cancer cell biology. Seminars in cell & developmental biology. 2012; 23(4): 352-61. Wolkers Monika C, Bensinger Steven J, Green Douglas R, Schoenberger Stephen P, Janssen Edith M Interleukin-2 rescues helpless effector CD8+ T cells by diminishing the susceptibility to TRAIL mediated death. Immunology letters. 2011; 139(1-2): 25-32. Beaven Simon W, Wroblewski Kevin, Wang Jiaohong, Hong Cynthia, Bensinger Steven, Tsukamoto Hide, Tontonoz Peter Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease. Gastroenterology. 2011; 140(3): 1052-62. Ribas Vicent, Drew Brian G, Le Jamie A, Soleymani Teo, Daraei Pedram, Sitz Daniel, Mohammad Laila, Henstridge Darren C, Febbraio Mark A, Hewitt Sylvia C, Korach Kenneth S, Bensinger Steven J, Hevener Andrea L Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108(39): 16457-62. Bensinger, S. J. Tontonoz, P. A Nurr1 pathway for neuroprotection. Cell. 2009; 137(1): 26-8. A. Gonzalez N Bensinger, S. J. Hong, C. Beceiro, S. Bradley, M. N. Zelcer, N. Deniz, J. Ramirez, C. Diaz, M. Gallardo, G. de Galarreta, C. R. Salazar, J. Lopez, F. Edwards, P. Parks, J. Andujar, M. Tontonoz, P. Castrillo, A. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity. 2009; 31(2): 245-58. A-Gonzalez Noelia, Bensinger Steven J, Hong Cynthia, Beceiro Susana, Bradley Michelle N, Zelcer Noam, Deniz Jose, Ramirez Cristina, Díaz Mercedes, Gallardo German, de Galarreta Carlos Ruiz, Salazar Jon, Lopez Felix, Edwards Peter, Parks John, Andujar Miguel, Tontonoz Peter, Castrillo Antonio Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity. 2009; 31(2): 245-58. Frank, M. J. Dawson, D. W. Bensinger, S. J. Hong, J. S. Knosp, W. M. Xu, L. Balatoni, C. E. Allen, E. L. Shen, R. R. Bar-Sagi, D. Martin, G. R. Teitell, M. A. Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas. Blood. 2009; 113(11): 2478-87. Hummasti, S. Hong, C. Bensinger, S. J. Tontonoz, P. HRASLS3 is a PPARgamma-selective target gene that promotes adipocyte differentiation. J Lipid Res. 2008; 49(12): 2535-44. Chao, L. C. Bensinger, S. J. Villanueva, C. J. Wroblewski, K. Tontonoz, P. Inhibition of adipocyte differentiation by Nur77, Nurr1, and Nor1. Mol Endocrinol. 2008; 22(12): 2596-608. Bensinger, S. J. Tontonoz, P. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature. 2008; 454(7203): 470-7. Bensinger, S. J. Bradley, M. N. Joseph, S. B. Zelcer, N. Janssen, E. M. Hausner, M. A. Shih, R. Parks, J. S. Edwards, P. A. Jamieson, B. D. Tontonoz, P. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell. 2008; 134(1): 97-111. Eck, S. C. Zhu, P. Pepper, M. Bensinger, S. J. Freedman, B. D. Laufer, T. M. Developmental alterations in thymocyte sensitivity are actively regulated by MHC class II expression in the thymic medulla. J Immunol. 2006; 176(4): 2229-37. Saleh, M. Mathison, J. C. Wolinski, M. K. Bensinger, S. J. Fitzgerald, P. Droin, N. Ulevitch, R. J. Green, D. R. Nicholson, D. W. Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature. 2006; 440(7087): 1064-8. Walsh, P. T. Buckler, J. L. Zhang, J. Gelman, A. E. Dalton, N. M. Taylor, D. K. Bensinger, S. J. Hancock, W. W. Turka, L. A. PTEN inhibits IL-2 receptor-mediated expansion of CD4+ CD25+ Tregs. J Clin Invest. 2006; 116(9): 2521-31. Janssen, E. M. Droin, N. M. Lemmens, E. E. Pinkoski, M. J. Bensinger, S. J. Ehst, B. D. Griffith, T. S. Green, D. R. Schoenberger, S. P. CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death. Nature. 2005; 434(7029): 88-93. Bensinger, S. J. Walsh, P. T. Zhang, J. Carroll, M. Parsons, R. Rathmell, J. C. Thompson, C. B. Burchill, M. A. Farrar, M. A. Turka, L. A. Distinct IL-2 receptor signaling pattern in CD4+CD25+ regulatory T cells. J Immunol. 2004; 172(9): 5287-96. Wu, Z. Bensinger, S. J. Zhang, J. Chen, C. Yuan, X. Huang, X. Markmann, J. F. Kassaee, A. Rosengard, B. R. Hancock, W. W. Sayegh, M. H. Turka, L. A. Homeostatic proliferation is a barrier to transplantation tolerance. Nat Med. 2004; 10(1): 87-92. Biju, M. P. Neumann, A. K. Bensinger, S. J. Johnson, R. S. Turka, L. A. Haase, V. H. Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes. Mol Cell Biol. 2004; 24(20): 9038-47. Burchill, M. A. Goetz, C. A. Prlic, M. O'Neil, J. J. Harmon, I. R. Bensinger, S. J. Turka, L. A. Brennan, P. Jameson, S. C. Farrar, M. A. Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells. J Immunol. 2003; 171(11): 5853-64. Adler, S. H. Bensinger, S. J. Turka, L. A. Stemming the tide of rejection. Nat Med. 2002; 8(2): 107-8. Bensinger, S. J. Bandeira, A. Jordan, M. S. Caton, A. J. Laufer, T. M. Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells. J Exp Med. 2001; 194(4): 427-38. Wekerle, T. Kurtz, J. Sayegh, M. Ito, H. Wells, A. Bensinger, S. Shaffer, J. Turka, L. Sykes, M. Peripheral deletion after bone marrow transplantation with costimulatory blockade has features of both activation-induced cell death and passive cell death. J Immunol. 2001; 166(4): 2311-6. Schiaffella, E. Fuschiotti, P. Bensinger, S. J. Mage, R. G. High RAD51 mRNA levels in young rabbit appendix. A role in B-cell gene conversion?. Immunogenetics. 1998; 48(2): 108-15. Callahan, H. L. Portal, I. F. Bensinger, S. J. Grogl, M. Leishmania spp: temperature sensitivity of promastigotes in vitro as a model for tropism in vivo. Exp Parasitol. 1996; 84(3): 400-9.