David A Fruman

Professor, Molecular Biology and Biochemistry
School of Biological Sciences

Associate Director, Cancer Research Institute

Director, UCI-GPS program for biomedical graduate professional development


B.S., Stanford University


PH.D., Harvard University

Phone: (949) 824-1947
Fax: (949) 824-8551
Email: dfruman@uci.edu

University of California, Irvine
Department of Molecular Biology and Biochemistry
3242 McGaugh Hall
Mail Code: 3900
Irvine, CA 92697

picture of David A Fruman

Research
Interests
signal transduction, immunology, cancer, leukemia, kinase, microarray
   
URL faculty.sites.uci.edu/frumanlab/
   
Academic
Distinctions
AAAS Fellow
Howard Hughes Medical Institute Predoctoral Fellow
Leukemia & Lymphoma Society Special Fellow
   
Appointments Postdoctoral Fellowship, Damon Runyon Cancer Research Fund (www.damonrunyon.org), 1995-1998
Special Fellowship, Leukemia & Lymphoma Society, 1998-2000
   
Research
Abstract
Lymphocytes circulate through the blood and lymphoid tissues in a resting state. Upon encountering antigens, they become activated to proliferate and differentiate. Lymphocytes also respond to other environmental cues, including cytokines and cell surface proteins on neighboring cells. The transmission of signals from outside the cell to the inside to modulate cell behavior is termed signal transduction.

Activation of phosphoinositide 3-kinase (PI3K) is a critical step in signal transduction pathways triggered by a variety of extracellular stimuli. The lipid products of PI3K serve as second messengers to recruit specific phospholipid-binding proteins to the plasma membrane. Excessive activation of PI3K signaling can cause transformation of certain cell types in vitro and has been observed in many tumors. Many isoforms of PI3K are expressed in mammalian cells, and many putative effector proteins have been identified. One crucial protein kinase downstream of PI3K is the mammalian target of rapamycin (mTOR). My laboratory is interested in the role of PI3K and mTOR in the function of normal cells and in the development of cancer cells. We are particularly interested in cells of the immune system, both normal lymphocytes and their transformed counterparts. Using gene targeting and pharmacological approaches we study the role of PI3K and mTOR in lymphocyte development, activation, and transformation.
   
Publications Deng, C, Lipstein, MM, Scott, L, Serrano, XO, Mangone, MA, Li, S, Vendome, J, Hao, Y, Xu, X, Deng, SX, Realubit, RB, Tatonetti, NP, Karan, C, Lentzsch, S, Fruman, DA, Honig, B, Landry, DW, O’Connor, OA. Silencing c-Myc translation as a therapeutic strategy through targeting PI3Kdelta and CK1epsilon in hematological malignancies. 2016. Blood, Epub Oct. 26.
   
  Pai, C, Walsh, CM, Fruman, DA. Context-specific function of S6K2 in helper T cell differentiation. 2016. J. Immunol., Epub Sept. 9.
   
  Hong, CA, Cho, SK, Edson, JA, Kim, J, Ingato, D, Pham, B, Chuang, A, Fruman D, Kwon, YJ. Viral/Nonviral chimeric nanoparticles to synergistically suppress leukemia proliferation via simultaneous gene transduction and silencing. 2016. ACS Nano, Epub Aug 5.
   
  Zeng, Z, Wang, RY, Qiu, YH, Mak, DH, Coombes, K, Yoo, SY, Zhang, Q, Jessen, K, Liu, Y, Rommel, C, Fruman, DA, Kantarjian, HM, Kornblau, SM, Andreeff, M, Konopleva, M. MLN0128, a novel mTOR kinase inhibitor, disrupts survival signaling and triggers apoptosis in AML and AML stem/progenitor cells. 2016. Oncotarget, Epub July 4
   
  So, L, Lee, J, Palafox, M, Mallya, S, Woxland, C, Arguello, M, Truitt, M, Sonenberg, N, Ruggero, D, Fruman, DA. The 4E-BP/eIF4E axis promotes rapamycin-sensitive growth and proliferation in lymphocytes. 2016. Science Signaling, 9: ra57
   
  Fruman, DA. mTOR signaling: New networks for ALL. 2016. Blood, 127:2658-9.
   
  Lee, JS, Vo, TT, Fruman, DA. Targeting mTOR for the treatment of B cell malignancies. 2016. Br. J. Clin. Pharmacol., 82: 1213-1228
   
  Lee, JS, Tang, SS, Ortiz, V, Vo, TT, Fruman, DA. MCL-1-independent mechanisms of synergy between dual PI3K/mTOR and BCL-2 inhibition in diffuse large B cell lymphoma. 2015. Oncotarget, 6: 35202-17.
   
  Beagle, BR, Nguyen, D, Mallya, S, Tang, SS, Lu, M, Zeng, A, Konopleva, M, Vo, TT, Fruman, DA. mTOR inhibitors synergize with histone deacetylase inhibitors to kill B-cell acute lymphoblastic leukemia cells. 2015. Oncotarget, 6: 2088-100.
   
  Limon, JJ, So, L, Jellbauer, S, Chiu, H, Corado, J, Sykes, S, Raffatellu, M, Fruman, DA. mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition. 2014. PNAS, Epub Nov. 10
   
  Yea, SS, So, L, Mallya, S, Lee, J, Rajasekaran, K, Malarkannan, S, Fruman, DA. Effects of novel isoform-selective phosphoinositide 3-kinase inhibitors on natural killer cell function. 2014. PLOS ONE, 9(6): e99486.
   
  Zhang, Z, Eckert, MA, Ali, MM, Liu, L, Kang, DK, Chang, E, Pone, EJ, Sender, L, Fruman, DA, Zhao, W. DNA-Scaffolded Multivalent Ligands to Modulate Cell Function. 2014. ChemBioChem, 15:1268-73.
   
  Walsh, CM, Fruman, DA. Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling. 2014. J. Clin. Invest., 124: 3688-90.
   
  Fruman, DA, Cantley, LC. Idelalisib: a PI3K delta inhibitor for B cell malignancies. 2014. New Engl. J. Med., 370: 1061-2.
   
  Mallya, S, Fitch, BA, Lee, JS, So, L, Janes, MR, Fruman, DA. Resistance to mTOR kinase inhibitors in lymphoma cells lacking 4EBP1. 2014. PLOS ONE, 9(2): e88865.
   
  Fruman, DA, Rommel, C. PI3K and cancer: lessons, challenges, and opportunities. 2014. Nat. Rev. Drug Discov., 13:140-56.
   
  Conley, ME, Fruman, DA. Can cancer drugs treat immunodeficiency? 2013. Science, 342:814-5.
   
  Yea, SS, Fruman, DA. Achieving cancer cell death with PI3K/mTOR-targeted therapies. 2013. Ann. NY Acad. Sci., 1280: 15-18.
   
  Zhang, Z, Ali, MM, Eckert, MA, Kang, DK, Chen, YY, Sender, L, Fruman, DA, Zhao, W. A polyvalent aptamer system for targeted drug delivery. 2013. Biomaterials. 34:9728-35.
   
  Lim, S, Saw, J, Zhang, M, Janes, MR, Lim, AQ, Chang, CT, Fruman, DA, Rizzieri, DA, Tan, SY, Fan, H, Chuah, CTH, Ong, ST. Targeting of the MNK-eIF4E axis in blast crisis chronic myelogenous leukemia inhibits leukemia stem cell function. 2013. PNAS Plus, 110: E2298-307.
   
  So, L, Yea, SS, Oak, JS, Manmadhan, A, Ke, QH, Janes, MR, Kessler, L, Kucharski, J, Li, LS, Martin, MB, Ren, P, Jessen, K, Rommel, C, Fruman, DA. Selective inhibition of phosphoinositide 3-kinase p110? preserves lymphocyte function. 2012. J. Biol. Chem., Epub Dec. 28
   
  Janes, MR, Vu, C, Mallya, S, Shieh, M, Limon, JJ, Lilly, MB, Sender, L, Si, LS, Martin, MB, Ren, P, Liu, Y, Rommel, C, Fruman, DA. Efficacy of the mTOR kinase inhibitor MLN0128/INK128 in models of B-cell acute lymphoblastic leukemia. 2012. Leukemia, Epub Oct. 23
   
  Zeng, Z, Shi, YX, Tsao, T, Qui, Y, Kornblau, SM, Baggerly, KA, Liu, W, Jessen, K, Liu, Y, Kantarjian, H, Rommel, C, Fruman, DA, Andreeff, M, Konopleva, M. Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. 2012. Blood, 120: 2679-89.
   
  Limon, JJ, Fruman, DA. Akt and mTOR in B cell activation and differentiation. 2012. Front. Immunol., 3: 228-240.
   
  So, L, Fruman, DA. PI 3-kinase signaling in the immune system. 2012. Biochem J, 442: 465-481.
   
  Current publications from Pubmed
   
  Fruman, DA, Rommel, C. PI3Kdelta inhibitors in cancer: rationale and serendipity merge in the clinic. 2011. Cancer Discovery, 1: 562-72.
   
  Romero Rosales, KR, Singh, G, Wu, K, Chen, J, Janes, MR, Lilly, MB, Peralta, ER, Siskind, LJ, Bennett, MJ, Fruman, DA, Edinger, AL. Sphingolipid-based drugs selectively kill cancer cells by downregulating nutrient transporters. 2011. Biochem. J., 439: 299-311.
   
  Janes, MR, Fruman, DA. The in vivo evaluation of active-site TOR inhibitors in models of BCR-ABL+ leukemia. In Thomas Weichhart, editor: Methods in Molecular Biology volume entitled “mTOR: Methods and Protocols”. 2012. Meth. Mol. Biol. 821: 251-65.
   
  Casey, SC, Nelson, EL, Turco, GM, Janes, MR, Fruman, DA, Blumberg, B. B-1 Cell Lymphoma in Mice Lacking the Steroid and Xenobiotic Receptor, SXR. 2011. Mol. Endocrinol., 25: 933-43.
   
  Yea, SS, Fruman, DA. New mTOR targets Grb attention. 2011. Science, 332: 1270-1.

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Summary: http://www.sciencemag.org/cgi/content/summary/332/6035/1270?ijkey=QbPRf76.puQqM&keytype=ref&siteid=sci

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Full Text: http://www.sciencemag.org/cgi/content/full/332/6035/1270?ijkey=QbPRf76.puQqM&keytype=ref&siteid=sci
   
  Beagle, B, Fruman, DA. Lipid kinase cousins cooperate to promote cancer. 2011. Cancer Cell, 19: 693-5.
   
  Fruman, DA. Regulatory subunits of class IA PI3K. In Peter K. Vogt, Christian Rommel, and Bart Vanhaesebroeck, editors: CTMI volume on “Phosphoinositide 3-kinase in health and disease”, 2010. Pp. 225-244. Also available on PubMed as Curr. Top. Microbiol. Immunol., 346: 225-244 (2011).
   
  Okkenhaug, K, Fruman, DA. PI3Ks in lymphocyte signaling and development. In Peter K. Vogt, Christian Rommel, and Bart Vanhaesebroeck, editors: CTMI volume on “Phosphoinositide 3-kinase in health and disease”, Springer-Verlag, 2010. Pp. 57-85. Also available on PubMed as Curr. Top. Microbiol. Immunol., 346: 57-85 (2011).
   
  Vu, C, Fruman, DA. Targeting TOR signaling in leukemia and lymphoma. 2010. Clin. Cancer Res. 16: 5374-80.
   
  Janes, MR, Fruman, DA. Targeting TOR dependency in cancer. 2010. Oncotarget 1: 69-76.
   
  Limon, JJ, Fruman, DA. B cell receptor signaling: Picky about PI3Ks. 2010. Sci. Signal. 3: pe25.

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Full Text: http://stke.sciencemag.org/cgi/content/full/sigtrans;3/134/pe25?ijkey=zWqqea0ay9YX2&keytype=ref&siteid=sigtrans
   
  Janes, MR, Limon, JJ, So, L, Chen, J, Lim, RJ, Chavez, MA, Vu, C, Lilly, MB, Mallya, S, Ong, ST, Konopleva, M, Martin, MB, Ren, P, Liu, Y, Rommel, C, Fruman, DA. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. 2010. Nat. Med. 16: 205-213.
   
  Chen, J, Blanc, C, Peng, SL, Fruman, DA. Foxo1 regulates marginal zone B cell development. 2010 Eur. J. Immunol., Epub May 6
   
  Alcazar, I, Barber, DF, Cortes, I, Fruman, DA, Carrera, AC. p85beta phosphoinositide 3-kinase regulates CD28 co-receptor function. 2009. Blood, 113: 3198-208.
   
  Janes, MR, Fruman, DA. Immune regulation by rapamycin: moving beyond T cells. 2009. Sci. Signal. 2: pe25.
   
  Oak, JS, Chen, J, Peralta, RQ, Deane, JA, Fruman, DA. The p85beta regulatory subunit of phosphoinositide 3-kinase has unique and redundant functions in B cells. 2009. Autoimmunity, 42: 447-458.
   
  Fabre, S, Carrette, F, Chen, J, Lang, C, Semichon, M, Denoyelle, C, Lazar, V, Cagnard, N, Dubart-Kupperschmitt, A, Mangeney, M, Fruman, DA, Bismuth, G. FOXO1 regulates L-selectin and a network of human T-cell homing molecules downstream of PI3K. 2008 J. Immunol., 181: 2980-9.
   
  Fruman, DA, Bismuth, G. Fine tuning the immune response with PI3K. 2009. Immunol. Rev. 228: 253-272.
   
  De Souza, AJ, Oak, JS, Jordanhazy, R, DeKruyff, RH, Fruman, DA, Kane, LP. Tim-1-mediated T cell activation requires recruitment and activation of PI 3-Kinase. 2008. J. Immunol., 180: 6518-26.
   
  Kharas, MG, Janes, MR, Scarfone, VM, Lilly, MB, Knight, ZA, Shokat, KS, Fruman, DA. Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of BCR-ABL+ leukemia cells. 2008. J. Clin. Invest., 118: 3038-50.
   
  Yusuf, I, Kharas, MG, Chen, J, Maruniak, A, Sareen, P, Tomayko, M, Shlomchik, MJ, Yang, VW, Kaestner, KH, Fruman, DA. KLF4 is a FOXO target gene that suppresses B cell proliferation. 2008. Int. Immunol, 20: 671-81.
   
  Oak, JS, Matheu, MP, Parker, I, Cahalan, MD, Fruman, DA. Lymphocyte cell motility: the twisting, turning tale of phosphoinositide 3-kinase. 2007. Biochem. Soc. Trans., 35: 1109-13.
   
  Donahue, AC, Kharas, MG, Fruman, DA. Measuring phosphoAkt and other PI3K-regulated phosphoproteins in primary lymphocytes. 2007. Methods Enzymol.,434: 131-54.
   
  Oak, JS, Fruman, DA. Role of phosphoinositide 3-kinase signaling in autoimmunity. 2007. Autoimmunity, 40(6): 433-41.
   
  Fruman, DA. The role of class I phosphoinositide 3-kinase in T cell function and autoimmunity. 2007 Biochem. Soc. Trans., 35(2): 177-80.
   
  Donahue, AC, Fruman, DA. Distinct signaling mechanisms activate the target of rapamycin in response to different B cell stimuli. 2007. Eur. J. Immunol., 37: 2923-36.
   
  Matheu, MP, Deane, JA, Parker, I, Fruman, DA, Cahalan, MD. Class IA phosphoinositide 3-kinase signaling is critical for basal lymphocyte motility in the lymph node. 2007. J. Immunol., 179: 2261-9.
   
  Fruman, DA. The role of class I phosphoinositide 3-kinase in T cell function and autoimmunity. 2007 Biochem. Soc. Trans., 35(2): 177-80.
   
  Deane, JA, Kharas, MG, Oak, JS, Stiles, LN, Luo, J, Moore, TI, Ji, H, Rommel, C, Cantley, LC, Lane, TE, Fruman, DA. T cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase regulatory isoforms. 2007. Blood, 109: 2894-902.
   
  Kharas, MG, Yusuf, I, Scarfone, VM, Yang, VW, Segre, JA, Huettner, CS, Fruman, DA. KLF4 opposes transformation of pre-B cells by ABL oncogenes. 2007. Blood, 109: 747-55.
   
  Oak, JS, Deane, JA, Kharas, MG, Luo, J, Lane, TE, Cantley, LC, Fruman, DA. Sjögren’s Syndrome-like disease in mice with T cells lacking phosphoinositide 3-kinase. 2006. Proc. Natl. Acad. Sci. 103: 16882-7.
   
  Chen, J, Yusuf, I, Andersen, H, Fruman, DA. FOXO transcription factors cooperate with dEF1 to activate growth suppressive genes in B lymphocytes. 2006. J. Immunol., 176: 2711-21.
   
  Kharas, MG, Fruman, DA. Abl oncogenes and PI3K: Mechanisms of activation and downstream effectors. 2005. Cancer Res., 65: 2047-53.
   
  Brachmann, S, Yballe, CM, DiFiore, PP, Deane, JA, Fruman, DA, Thomas, SM, Cantley, LC. The role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement. 2005. Mol. Cell. Biol., 25: 2593-606.
   
  Zhu, X, Hart, R, Kim, JW, Lee, SY, Chang, MS, Cao, YA, Mock, D, Ke, E, Saunders, B, Alexander, A, Grossoehme, J, Lin, KM, Yan, Z, Hsueh, R, Fruman, DA, Subramaniam, S, Sternweis, P, Simon, MI Choi, S. Analysis of the major patterns of B cell gene expression changes in response to short-term stimulation with 33 single ligands. 2004. J. Immunol., 173: 7141–7149.
   
  Donahue, AC, Hess, KL, Ng, KL, Fruman, DA. Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alpha. 2004. Int. Immunol., 16: 1789-98.
   
  Hess, KL, Donahue, AC, Ng, KL, Moore, TI, Oak, J, Fruman, DA. The p85alpha isoform of phosphoinositide 3-kinase is essential for a subset of B cell receptor-initiated signaling responses. 2004. Eur. J. Immunol., 34: 2968-76.
   
  Deane, JA, Trifilo, MJ, Yballe, CM, Choi, S, Lane, TE, Fruman, DA. Enhanced T cell proliferation in mice lacking the p85b subunit of phosphoinositide 3-kinase. 2004. J. Immunol., 172: 6615-25.
   
  Yusuf, I, Zhu, X, Kharas, MG, Chen, J, Fruman, DA. Optimal B cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors. 2004. Blood, 104: 784-7.
   
  Kharas, MG, Deane, JA, Wong, S, O’Bosky, KR, Rosenberg, N, Witte, ON, Fruman, DA. Phosphoinositide 3-kinase is essential for Abl oncogene mediated transformation of B lineage cells. 2004. Blood, 103: 4268-75.
   
  Fruman, DA. PI3K and its targets in B cell and T cell signaling. 2004. Curr Opin. Immunol., 16: 314-20.
   
  Donahue, AC, Fruman, DA. PI3K signaling controls cell fate at many points in B lymphocyte development and activation. 2004. Semin. Cell Dev. Biol., 15: 183-97.
   
  Deane, JD, Fruman, DA. Phosphoinositide 3-kinase: diverse roles in immune cell activation. 2004. Annu. Rev. Immunol., 22: 563-98.
   
  Fruman, DA. Towards and understanding of isoform specificity in phosphoinositide 3-kinase signaling in lymphocytes. 2004. Biochem. Soc. Trans. 32: 315-9.
   
  Donahue, AC, Fruman, DA. Proliferation and survival of activated B cells requires sustained antigen receptor signaling and phosphoinositide 3-kinase activation. 2003. J. Immunol. 170: 5851-60.
   
  Yusuf, I, Fruman, DA. Regulation of quiescence in lymphocytes. 2003. Trends Immunol., 24:380-6.
   
  Fruman, DA, Ferl, GZ, An, SS, Donahue, AC, Satterthwaite, AB, Witte, ON. Phosphoinositide 3-kinase and Bruton’s tyrosine kinase regulate overlapping sets of genes in B
lymphocytes. (2002) Proc. Natl. Acad. Sci. USA 99: 359-64.
   
  Fruman, DA, Cantley, LC. Phosphoinositide 3-kinase in immunological systems. (2002) Semin. Immunol., 14: 7-18.
   
  Mauvais-Jarvis, F, Ueki, K, Fruman, DA, Hirschman, MF, Sakamoto, K, Goodyear, LJ, Iannacone, M, Accili, D, Cantley, LC, Kahn, CR. Reduced expression of the murine p85a subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. 2002. J. Clin. Invest. 109: 141-9.
   
  Fruman, DA, Satterthwaite, AB, Witte, ON. Xid-like phenotypes: a B cell signalosome takes shape. (2000) Immunity 13: 1-3.
   
  Fruman, DA, Mauvais-Jarvis, F, Pollard, DA, Brazil, D, Bronson, RT, Kahn, CR, Cantley, LC. Hypoglycemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85alpha. (2000) Nature Genetics 26: 379-82.
   
  Fruman, DA, Rameh, LE, Cantley, LC. Phosphoinositide binding domains: Embracing 3-phosphate. (1999) Cell 97: 817-20.
   
  Fruman, DA, Snapper, SB, Yballe, CM, Yu, JY, Davidson, L, Alt, FW, Cantley, LC. Impaired B cell development and function in the absence of phosphoinositide 3-kinase p85a. (1999) Science 283: 393-7
   
Professional
Societies
American Association for the Advancement of Science (AAAS)
American Association of Immunologists
American Association for Cancer Research
Faculty of 1000, Biology
   
Other Experience Visiting Professor
Cochin Institute, Paris, France 2006—2007

Director, Graduate Program in Cellular & Molecular Biosciences
Schools of Biological Sciences and Medicine 2011—pres

Graduate Programs Cellular and Molecular Biosciences

   
Research Center Center for Immunology
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=4541
   
Last updated 11/22/2016