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 David A Fruman

University of California

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

PHONE: (949) 824-1947
FAX: (949) 824-8551

E-MAIL: dfruman@uci.edu

 

David A Fruman
Associate Professor, Molecular Biology and Biochemistry
School of Biological Sciences
 Associate Director, Institute for Immunology
B.S., Stanford University
PH.D., Harvard University
Research Interests
signal transduction, immunology, cancer, leukemia, kinase, microarray

Faculty/lab web:
http://mbb.bio.uci.edu/fruman/
 
Graduate Programs:
 Cellular and Molecular Biosciences
 
Professional Society American Association for the Advancement of Science (AAAS) American Association of Immunologists American Association for Cancer Research Faculty of 1000, Biology
 
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. My laboratory is interested in the role of PI3K and its effectors 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 specific PI3K proteins and subgroups in lymphocyte development, activation, motility and transformation.

Another interest is to identify and characterize transcription factors that promote lymphocyte quiescence. Using transcriptional profiling by DNA microarray, we have identified the FOXO and KLF transcription factor families as candidate quiescence factors in B cells. Ongoing studies aim to elucidate the function and target genes of individual FOXO and KLF isoforms.


Other Experience
Visiting Professor, Cochin Institute, Paris, France, 2006—2007
Updated: Last Updated: 08/20/2009

  Janes, MR, Fruman, DA. Immune regulation by rapamycin: moving beyond T cells. 2009. Sci. Signal. 2: pe25.

Fruman, DA, Bismuth, G. Fine tuning the immune response with PI3K. 2009. Immunol. Rev. 228: 253-272.

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.

Alcazar, I, Barber, DF, Cortes, I, Fruman, DA, Carrera, AC. p85beta phosphoinositide 3-kinase regulates CD28 co-receptor function. 2009. Blood, 113: 3198-208.

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.

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.

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.

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.

Janes, MR, Fruman, DA. Immune regulation by rapamycin: moving beyond T cells. 2009. Sci. Signal. 2: pe25.

Alcazar, I, Barber, DF, Cortes, I, Fruman, DA, Carrera, AC. p85beta phosphoinositide 3-kinase regulates CD28 co-receptor function. 2009. Blood, 113: 3198-208.

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
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