Mark R. Boothby, M.D., Ph.D.

Faculty Appointments
Professor of Pathology, Microbiology and Immunology Professor of Medicine
M.D., Molecular Biology, Washington University, Saint Louis, MissouriPh.D., Molecular Biology, Washington University, Saint Louis, MissouriB.S., Molecular Biology, University of Wisconsin, Madison, Wisconsin
Office Address
AA-4214 MCN
AA-4220 MCN
TN 37232-2363
Research Description
We investigate mechanisms by which signaling and transcription factors regulate cell growth, differentiation, and survival. The lab dissects these questions through an integration of genetic manipulations, biochemical studies, and analyses of function in immunity.

Potential projects (2016):
1. Signaling and immune function mediated sensors of cellular environment (metabolism, oxygenation, nutrients) and metabolites. Active work in this area includes dissection of how AMPK, a sensor of energy deficiency, hypoxia-induced factors and their regulators, and the Akt / mTOR axis of serine-threonine kinases impact the qualities of humoral immunity and immune memory. We have identified evidence of an important role for a novel complex involving the kinase mTOR - "mammalian target of rapamycin" (rapamycin being an important immune suppressant drug) - in T and B cell differentiation and are dissecting molecular mechanisms involved in these findings as well as impact on immunity, including T cell memory, B cell development and function in models of vaccination and anti-pathogen immunity, and in autoimmunity.

2. Investigation of a novel protein cloned in the lab, which enhances the function of a transcription factor central to allergic diseases and asthma. We are using knockout mice deficient in this cofactor, a novel ADP-ribosyltransferase, to explore how this protein impacts signaling to the regulation of programmed cell death, cellular metabolism, B lymphoma pathophysiology (because of connections to a related protein affecting the outcome of lymphocyte cancers), and the impact of this protein on vaccination and immunity to pathogens.

An earlier focus of the research has been on the differentiation of naive T helper lymphocytes into activated cells that have acquired effector functions, i.e., the ability to express new genes that orchestrate immune responses. One subset of effector T helper cells is called the Th2 subset. Differentiation into Th2 effectors is driven by the cytokine IL-4, so one major area of study in the lab is the transduction of signals by the IL-4 receptor and the means by which IL-4 regulates gene transcription. We cloned and knocked out a gene encoding a novel protein that enhances IL-4 induction of transcription and pro-survival signaling. Future studies will include determining the biochemical and function roles of this novel transcriptional coregulator.

We recently discovered that memory Th2 cells permit an unexpected flexibility in regulation of the Th1 cytokine gene for IFN-gamma while at the same time retaining commitment to expression of the characteristic Th2 cytokine genes (IL-4, IL-5, and IL-13). We will dissect molecular mechanisms for both flexibility and commitment, using analyses of transcription factor knockouts as well as of chromatin (epigenetic DNA methylation as well as histone modifications).

A second class of effector T cells is known as the Th1 subset, of which a hallmark is the activation of the gene encoding the inflammatory cytokine interferon-gamma. We dicsovered that the transcription factor NF-kappaB is particularly important in the Th1 response but not in responses mediated by Th2 cells, and have identified an orderly sequence of molecular events leading to remodeling of the IFN-gamma promoter. Using analyses of chromatin modifications and structure in the interferon gamma locus, we are in the process of determining the mechanisms by which the gene is regulated in primary T helper subsets, memory CD4 cells, and exploring the impact of these processes on differentiation of another autoimmunity-promoting class of T cells (Th17 cells).

Finally, we are in the midst of developing exciting insights for T and B lymphocytes in relation to the signaling pathways described above and dissecting how these pathways impact the generation and persistence of antibody-producing cells and immune memory.
Research Keywords
Signaling and gene regulation mechanisms in immune system hematopoietic cells, especially those of B and T lymphoid lineages. Lymphoid lineage cells are the most central means of regulating characteristics of immunity and auto-immunity, and they also are vital in the inflammation and pathophysiology of most of the main disease burden in the US (atherosclerotic vascular disease with heart attacks and strokes, obesity, diabetes, and cancer), The lab seeks to identify new signal transduction, transcription, and chromatin or epigenetic ways in which lymphoid lineage cells are regulated, with active investigations in immunity, auto-immunity (autoimmunity) and the ways in which sustained antibody responses are evoked since antibody levels are crucial in the efficacy of vaccines and are key components in a variety of autoimmune diseases.
Zhou W, Zhang J, Goleniewska K, Dulek DE, Toki S, Newcomb DC, Cephus JY, Collins RD, Wu P, Boothby MR, Peebles RS. Prostaglandin I2 Suppresses Proinflammatory Chemokine Expression, CD4 T Cell Activation, and STAT6-Independent Allergic Lung Inflammation. J. Immunol [print-electronic]. 2016 Jul 7/25/2016; PMID: 27456482, PII: jimmunol.1501063, DOI: 10.4049/jimmunol.1501063, ISSN: 1550-6606.

Boothby MR, Raybuck AL, Cho SH. Complementing T Cells' Functions: Bringing in Metabolism Matters. Immunity. 2015 Jun 6/16/2015; 42(6): 977-9. PMID: 26084014, PII: S1074-7613(15)00230-7, DOI: 10.1016/j.immuni.2015.06.008, ISSN: 1097-4180.

Wang S, Amato KR, Song W, Youngblood V, Lee K, Boothby M, Brantley-Sieders DM, Chen J. Regulation of endothelial cell proliferation and vascular assembly through distinct mTORC2 signaling pathways. Mol. Cell. Biol [print-electronic]. 2015 Apr; 35(7): 1299-313. PMID: 25582201, PMCID: PMC4355541, PII: MCB.00306-14, DOI: 10.1128/MCB.00306-14, ISSN: 1098-5549.

Yang J, Hawkins OE, Barham W, Gilchuk P, Boothby M, Ayers GD, Joyce S, Karin M, Yull FE, Richmond A. Myeloid IKKß promotes antitumor immunity by modulating CCL11 and the innate immune response. Cancer Res [print-electronic]. 2014 Dec 12/15/2014; 74(24): 7274-84. PMID: 25336190, PMCID: PMC4349570, PII: 0008-5472.CAN-14-1091, DOI: 10.1158/0008-5472.CAN-14-1091, ISSN: 1538-7445.

Iqbal MB, Johns M, Cao J, Liu Y, Yu SC, Hyde GD, Laffan MA, Marchese FP, Cho SH, Clark AR, Gavins FN, Woollard KJ, Blackshear PJ, Mackman N, Dean JL, Boothby M, Haskard DO. PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression. Blood [print-electronic]. 2014 Dec 12/4/2014; 124(24): 3646-55. PMID: 25293769, PMCID: PMC4256914, PII: blood-2014-07-588046, DOI: 10.1182/blood-2014-07-588046, ISSN: 1528-0020.

Marcais A, Blevins R, Graumann J, Feytout A, Dharmalingam G, Carroll T, Amado IF, Bruno L, Lee K, Walzer T, Mann M, Freitas AA, Boothby M, Fisher AG, Merkenschlager M. MicroRNA-mediated regulation of mTOR complex components facilitates discrimination between activation and anergy in CD4 T cells. J. Exp. Med [print-electronic]. 2014 Oct 10/20/2014; 211(11): 2281-95. PMID: 25311506, PMCID: PMC4203951, PII: jem.20132059, DOI: 10.1084/jem.20132059, ISSN: 1540-9538.

Lee K, Heffington L, Jellusova J, Nam KT, Raybuck A, Cho SH, Thomas JW, Rickert RC, Boothby M. Requirement for Rictor in homeostasis and function of mature B lymphoid cells. Blood [print-electronic]. 2013 Oct 10/3/2013; 122(14): 2369-79. PMID: 23958952, PMCID: PMC3790507, PII: blood-2013-01-477505, DOI: 10.1182/blood-2013-01-477505, ISSN: 1528-0020.

Cho SH, Raybuck A, Wei M, Erickson J, Nam KT, Cox RG, Trochtenberg A, Thomas JW, Williams J, Boothby M. B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-ribosyl)transferase. J. Immunol [print-electronic]. 2013 Sep 9/15/2013; 191(6): 3169-78. PMID: 23956424, PMCID: PMC3770464, PII: jimmunol.1301106, DOI: 10.4049/jimmunol.1301106, ISSN: 1550-6606.

Lee K, Boyd KL, Parekh DV, Kehl-Fie TE, Baldwin HS, Brakebusch C, Skaar EP, Boothby M, Zent R. Cdc42 promotes host defenses against fatal infection. Infect. Immun [print-electronic]. 2013 Aug; 81(8): 2714-23. PMID: 23690402, PMCID: PMC3719566, PII: IAI.01114-12, DOI: 10.1128/IAI.01114-12, ISSN: 1098-5522.

Williams CL, Schilling MM, Cho SH, Lee K, Wei M, Aditi, Boothby M. STAT4 and T-bet are required for the plasticity of IFN-¿ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation. J. Immunol [print-electronic]. 2013 Jul 7/15/2013; 191(2): 678-87. PMID: 23761633, PMCID: PMC3702659, PII: jimmunol.1203360, DOI: 10.4049/jimmunol.1203360, ISSN: 1550-6606.

Volanakis EJ, Boothby MR, Sherr CJ. Epigenetic regulation of the Ink4a-Arf (Cdkn2a) tumor suppressor locus in the initiation and progression of Notch1-driven T cell acute lymphoblastic leukemia. Exp. Hematol [print-electronic]. 2013 Apr; 41(4): 377-86. PMID: 23178376, PMCID: PMC3860824, PII: S0301-472X(12)00543-7, DOI: 10.1016/j.exphem.2012.11.006, ISSN: 1873-2399.

Boothby M, Williams CL. The Goldilocks effect. Sci Transl Med. 2012 Dec 12/5/2012; 4(163): 163fs42. PMID: 23220631, PII: 4/163/163fs42, DOI: 10.1126/scitranslmed.3005280, ISSN: 1946-6242.

Yang J, Kantrow S, Sai J, Hawkins OE, Boothby M, Ayers GD, Young ED, Demicco EG, Lazar AJ, Lev D, Richmond A. INK4a/ARF [corrected] inactivation with activation of the NF-¿B/IL-6 pathway is sufficient to drive the development and growth of angiosarcoma. Cancer Res [print-electronic]. 2012 Sep 9/15/2012; 72(18): 4682-95. PMID: 22836752, PMCID: PMC3459578, PII: 0008-5472.CAN-12-0440, DOI: 10.1158/0008-5472.CAN-12-0440, ISSN: 1538-7445.

Collier SP, Collins PL, Williams CL, Boothby MR, Aune TM. Cutting edge: influence of Tmevpg1, a long intergenic noncoding RNA, on the expression of Ifng by Th1 cells. J. Immunol [print-electronic]. 2012 Sep 9/1/2012; 189(5): 2084-8. PMID: 22851706, PMCID: PMC3424368, PII: jimmunol.1200774, DOI: 10.4049/jimmunol.1200774, ISSN: 1550-6606.

Zhuang G, Song W, Amato K, Hwang Y, Lee K, Boothby M, Ye F, Guo Y, Shyr Y, Lin L, Carbone DP, Brantley-Sieders DM, Chen J. Effects of cancer-associated EPHA3 mutations on lung cancer. J. Natl. Cancer Inst [print-electronic]. 2012 Aug 8/8/2012; 104(15): 1182-97. PMID: 22829656, PMCID: PMC3611812, PII: djs297, DOI: 10.1093/jnci/djs297, ISSN: 1460-2105.

Lee K, Nam KT, Cho SH, Gudapati P, Hwang Y, Park DS, Potter R, Chen J, Volanakis E, Boothby M. Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia. J. Exp. Med [print-electronic]. 2012 Apr 4/9/2012; 209(4): 713-28. PMID: 22473959, PMCID: PMC3328370, PII: jem.20111470, DOI: 10.1084/jem.20111470, ISSN: 1540-9538.

Boothby M. NIH Portfolio Allocation, Lemmings, and the Silent Spring: A Time-Capsule Commentary & Its Update. F1000Res. 2012; 1: 5. PMID: 24358813, PMCID: PMC3752635, DOI: 10.12688/f1000research.1-5.v1, ISSN: 2046-1402.

Gordy LE, Bezbradica JS, Flyak AI, Spencer CT, Dunkle A, Sun J, Stanic AK, Boothby MR, He YW, Zhao Z, Van Kaer L, Joyce S. IL-15 regulates homeostasis and terminal maturation of NKT cells. J. Immunol [print-electronic]. 2011 Dec 12/15/2011; 187(12): 6335-45. PMID: 22084435, PMCID: PMC3237743, PII: jimmunol.1003965, DOI: 10.4049/jimmunol.1003965, ISSN: 1550-6606.

Cho SH, Ahn AK, Bhargava P, Lee CH, Eischen CM, McGuinness O, Boothby M. Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2011 Sep 9/20/2011; 108(38): 15972-7. PMID: 21911376, PMCID: PMC3179111, PII: 1017082108, DOI: 10.1073/pnas.1017082108, ISSN: 1091-6490.

Dunaway CM, Hwang Y, Lindsley CW, Cook RS, Wu JY, Boothby M, Chen J, Brantley-Sieders DM. Cooperative signaling between Slit2 and Ephrin-A1 regulates a balance between angiogenesis and angiostasis. Mol. Cell. Biol [print-electronic]. 2011 Feb; 31(3): 404-16. PMID: 21135133, PMCID: PMC3028625, PII: MCB.00667-10, DOI: 10.1128/MCB.00667-10, ISSN: 1098-5549.

Boothby M. CRACking the code without Rosetta: molecular regulation of calcium-stimulated gene transcription after T cell activation. J. Immunol. 2010 Nov 11/1/2010; 185(9): 4969-71. PMID: 20962264, PII: 185/9/4969, DOI: 10.4049/jimmunol.1090097, ISSN: 1550-6606.

Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson MA, Boothby M. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity. 2010 Jun 6/25/2010; 32(6): 743-53. PMID: 20620941, PMCID: PMC2911434, PII: S1074-7613(10)00205-0, DOI: 10.1016/j.immuni.2010.06.002, ISSN: 1097-4180.

Boothby M. The calculus of integrating differentiation: timing control of T-bet. Immunity. 2009 May; 30(5): 666-8. PMID: 19464989, PII: S1074-7613(09)00194-0, DOI: 10.1016/j.immuni.2009.04.008, ISSN: 1097-4180.

Cho SH, Goenka S, Henttinen T, Gudapati P, Reinikainen A, Eischen CM, Lahesmaa R, Boothby M. PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells. Blood [print-electronic]. 2009 Mar 3/12/2009; 113(11): 2416-25. PMID: 19147789, PMCID: PMC2656269, PII: blood-2008-03-144121, DOI: 10.1182/blood-2008-03-144121, ISSN: 1528-0020.

Adeeku E, Gudapati P, Mendez-Fernandez Y, Van Kaer L, Boothby M. Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Jul 7/8/2008; 105(27): 9307-12. PMID: 18591677, PMCID: PMC2453725, PII: 0704807105, DOI: 10.1073/pnas.0704807105, ISSN: 1091-6490.

Goenka S, Cho SH, Boothby M. Collaborator of Stat6 (CoaSt6)-associated poly(ADP-ribose) polymerase activity modulates Stat6-dependent gene transcription. J. Biol. Chem [print-electronic]. 2007 Jun 6/29/2007; 282(26): 18732-9. PMID: 17478423, PII: M611283200, DOI: 10.1074/jbc.M611283200, ISSN: 0021-9258.

Zhang F, Boothby M. T helper type 1-specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-gamma promoter are Stat4 dependent. J. Exp. Med [print-electronic]. 2006 Jun 6/12/2006; 203(6): 1493-505. PMID: 16717115, PMCID: PMC2118309, PII: jem.20060066, DOI: 10.1084/jem.20060066, ISSN: 0022-1007.

Talati M, Meyrick B, Peebles RS, Davies SS, Dworski R, Mernaugh R, Mitchell D, Boothby M, Roberts LJ, Sheller JR. Oxidant stress modulates murine allergic airway responses. Free Radic. Biol. Med [print-electronic]. 2006 Apr 4/1/2006; 40(7): 1210-9. PMID: 16545689, PII: S0891-5849(05)00710-0, DOI: 10.1016/j.freeradbiomed.2005.11.012, ISSN: 0891-5849.

Goenka S, Boothby M. Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2006 Mar 3/14/2006; 103(11): 4210-5. PMID: 16537510, PMCID: PMC1449672, PII: 0506981103, DOI: 10.1073/pnas.0506981103, ISSN: 0027-8424.

Stephenson LM, Park DS, Mora AL, Goenka S, Boothby M. Sequence motifs in IL-4R alpha mediating cell-cycle progression of primary lymphocytes. J. Immunol. 2005 Oct 10/15/2005; 175(8): 5178-85. PMID: 16210622, PII: 175/8/5178, ISSN: 0022-1767.

Jones RG, Saibil SD, Pun JM, Elford AR, Bonnard M, Pellegrini M, Arya S, Parsons ME, Krawczyk CM, Gerondakis S, Yeh WC, Woodgett JR, Boothby MR, Ohashi PS. NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo. J. Immunol. 2005 Sep 9/15/2005; 175(6): 3790-9. PMID: 16148125, PII: 175/6/3790, ISSN: 0022-1767.

Corn RA, Hunter C, Liou HC, Siebenlist U, Boothby MR. Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation. J. Immunol. 2005 Aug 8/15/2005; 175(4): 2102-10. PMID: 16081776, PII: 175/4/2102, ISSN: 0022-1767.

Tong Y, Aune T, Boothby M. T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-gamma promoter via a conserved T-box half-site. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Feb 2/8/2005; 102(6): 2034-9. PMID: 15684083, PMCID: PMC548570, PII: 0409510102, DOI: 10.1073/pnas.0409510102, ISSN: 0027-8424.

Corn RA, Hunter C, Liou HC, Siebenlist U, Boothby M. Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation. J Immunol. 2005; 175((Aug 15 (4))): 2102-10.

Aronica MA, Swaidani S, Zhang YH, Mitchell D, Mora AL, McCarthy S, O'Neal J, Topham D, Sheller JR, Boothby M. Susceptibility to allergic lung disease regulated by recall responses of dual-receptor memory T cells. J. Allergy Clin. Immunol. 2004 Dec; 114(6): 1441-8. PMID: 15577850, PII: S0091674904022353, DOI: 10.1016/j.jaci.2004.08.025, ISSN: 0091-6749.

Heller NM, Matsukura S, Georas SN, Boothby MR, Stellato C, Schleimer RP. Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells. Clin. Exp. Allergy. 2004 Nov; 34(11): 1690-700. PMID: 15544592, PII: CEA2091, DOI: 10.1111/j.1365-2222.2004.02091.x, ISSN: 0954-7894.

Heller NM, Matsukura S, Georas SN, Boothby MR, Rothman PB, Stellato C, Schleimer RP. Interferon-gamma inhibits STAT6 signal transduction and gene expression in human airway epithelial cells. Am. J. Respir. Cell Mol. Biol [print-electronic]. 2004 Nov; 31(5): 573-82. PMID: 15297269, PII: 2004-0195OC, DOI: 10.1165/rcmb.2004-0195OC, ISSN: 1044-1549.

Stephenson L, Johns MH, Woodward E, Mora AL, Boothby M. An IL-4R alpha allelic variant, I50, acts as a gain-of-function variant relative to V50 for Stat6, but not Th2 differentiation. J. Immunol. 2004 Oct 10/1/2004; 173(7): 4523-8. PMID: 15383584, PII: 173/7/4523, ISSN: 0022-1767.

Stanic AK, Bezbradica JS, Park JJ, Van Kaer L, Boothby MR, Joyce S. Cutting edge: the ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase C theta and NF-kappa B. J. Immunol. 2004 Apr 4/15/2004; 172(8): 4667-71. PMID: 15067039, ISSN: 0022-1767.

Aronica MA, McCarthy S, Swaidani S, Mitchell D, Goral M, Sheller JR, Boothby M. Recall helper T cell response: T helper 1 cell-resistant allergic susceptibility without biasing uncommitted CD4 T cells. Am. J. Respir. Crit. Care Med [print-electronic]. 2004 Mar 3/1/2004; 169(5): 587-95. PMID: 14617509, PII: 200301-100OC, DOI: 10.1164/rccm.200301-100OC, ISSN: 1073-449X.

Stanic AK, Bezbradica JS, Park JJ, Matsuki N, Mora AL, Van Kaer L, Boothby MR, Joyce S. NF-kappa B controls cell fate specification, survival, and molecular differentiation of immunoregulatory natural T lymphocytes. J. Immunol. 2004 Feb 2/15/2004; 172(4): 2265-73. PMID: 14764695, ISSN: 0022-1767.

Aronica MA, Swaidani, S, Zhang YH, Mitchell D, Mora AL, McCarthy S, Topham D, Sheller JR, and Boothby M. Susceptibility to allergic lung disease regulated by recall responses of dual-specificity memory T cells. J Allergy and Clin Immunol. 2004; in press.

Goenka S, Marlar C, Schindler U, Boothby M. Differential roles of C-terminal activation motifs in the establishment of Stat6 transcriptional specificity. J. Biol. Chem [print-electronic]. 2003 Dec 12/12/2003; 278(50): 50362-70. PMID: 14519766, PII: M305854200, DOI: 10.1074/jbc.M305854200, ISSN: 0021-9258.

Mora AL, Corn RA, Stanic AK, Goenka S, Aronica M, Stanley S, Ballard DW, Joyce S, Boothby M. Antiapoptotic function of NF-kappaB in T lymphocytes is influenced by their differentiation status: roles of Fas, c-FLIP, and Bcl-xL. Cell Death Differ. 2003 Sep; 10(9): 1032-44. PMID: 12934078, PII: 4401257, DOI: 10.1038/sj.cdd.4401257, ISSN: 1350-9047.

Mora AL, Stephenson LM, Enerson B, Youn J, Keegan AD, Boothby M. New programming of IL-4 receptor signal transduction in activated T cells: Stat6 induction and Th2 differentiation mediated by IL-4Ralpha lacking cytoplasmic tyrosines. J. Immunol. 2003 Aug 8/15/2003; 171(4): 1891-900. PMID: 12902491, ISSN: 0022-1767.

Corn RA, Aronica MA, Zhang F, Tong Y, Stanley SA, Kim SR, Stephenson L, Enerson B, McCarthy S, Mora A, Boothby M. T cell-intrinsic requirement for NF-kappa B induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response. J. Immunol. 2003 Aug 8/15/2003; 171(4): 1816-24. PMID: 12902482, ISSN: 0022-1767.

Kelly-Welch AE, Hanson EM, Boothby MR, Keegan AD. Interleukin-4 and interleukin-13 signaling connections maps. Science. 2003 Jun 6/6/2003; 300(5625): 1527-8. PMID: 12791978, PII: 300/5625/1527, DOI: 10.1126/science.1085458, ISSN: 1095-9203.

Tato CM, Villarino A, Caamaño JH, Boothby M, Hunter CA. Inhibition of NF-kappa B activity in T and NK cells results in defective effector cell expansion and production of IFN-gamma required for resistance to Toxoplasma gondii. J. Immunol. 2003 Mar 3/15/2003; 170(6): 3139-46. PMID: 12626571, ISSN: 0022-1767.

Yang L, Yamagata N, Yadav R, Brandon S, Courtney RL, Morrow JD, Shyr Y, Boothby M, Joyce S, Carbone DP, Breyer RM. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J. Clin. Invest. 2003 Mar; 111(5): 727-35. PMID: 12618527, PMCID: PMC151895, DOI: 10.1172/JCI16492, ISSN: 0021-9738.

Zhou P, Hwang KW, Palucki DA, Guo Z, Boothby M, Newell KA, Alegre ML. Impaired NF-kappaB activation in T cells permits tolerance to primary heart allografts and to secondary donor skin grafts. Am. J. Transplant. 2003 Feb; 3(2): 139-47. PMID: 12603209, PII: 033, ISSN: 1600-6135.

Boothby M. Signaling advances from immunogenetics to immunogenomics. Genome Biol [print-electronic]. 2003; 4(12): 239. PMID: 14659009, PMCID: PMC329411, PII: gb-2003-4-12-239, DOI: 10.1186/gb-2003-4-12-239, ISSN: 1474-760X.

Finn PW, He H, Ma C, Mueller T, Stone JR, Liou HC, Boothby MR, Perkins DL. Molecular profiling of the role of the NF-kappaB family of transcription factors during alloimmunity. J. Leukoc. Biol. 2002 Nov; 72(5): 1054-62. PMID: 12429729, ISSN: 0741-5400.

Soutto M, Zhang F, Enerson B, Tong Y, Boothby M, Aune TM. A minimal IFN-gamma promoter confers Th1 selective expression. J. Immunol. 2002 Oct 10/15/2002; 169(8): 4205-12. PMID: 12370350, ISSN: 0022-1767.

Harlin H, Podack E, Boothby M, Alegre ML. TCR-independent CD30 signaling selectively induces IL-13 production via a TNF receptor-associated factor/p38 mitogen-activated protein kinase-dependent mechanism. J. Immunol. 2002 Sep 9/1/2002; 169(5): 2451-9. PMID: 12193714, ISSN: 0022-1767.

Harlin H, Hwang KW, Palucki DA, Kim O, Thompson CB, Boothby M, Alegre ML. CTLA-4 engagement regulates NF-kappaB activation in vivo. Eur. J. Immunol. 2002 Aug; 32(8): 2095-104. PMID: 12209621, DOI: 10.1002/1521-4141(200208)32:8<2095::AID-IMMU2095>3.0.CO;2-E, ISSN: 0014-2980.

Haley KJ, Ciota A, Contreras JP, Boothby MR, Perkins DL, Finn PW. Alterations in lung collectins in an adaptive allergic immune response. Am. J. Physiol. Lung Cell Mol. Physiol. 2002 Mar; 282(3): L573-84. PMID: 11839554, DOI: 10.1152/ajplung.00117.2001, ISSN: 1040-0605.

Chen Y, Rosloniec E, Price J, Boothby M, Chen J. Constitutive expression of BCL-X(L) in the T lineage attenuates collagen-induced arthritis in Bcl-X(L) transgenic mice. Arthritis Rheum. 2002 Feb; 46(2): 514-21. PMID: 11840455, PII: 10.1002/art.10128, ISSN: 0004-3591.

Boothby M and Aronica MA. Transcription regulation, allergic responses, and asthma. Immunol Allergy Clin N. Amer. 2002; 22: 871-89.

Zamorano J, Mora AL, Boothby M, Keegan AD. NF-kappa B activation plays an important role in the IL-4-induced protection from apoptosis. Int. Immunol. 2001 Dec; 13(12): 1479-87. PMID: 11717189, ISSN: 0953-8178.

Finn PW, Stone JR, Boothby MR, Perkins DL. Inhibition of NF-kappaB-dependent T cell activation abrogates acute allograft rejection. J. Immunol. 2001 Nov 11/15/2001; 167(10): 5994-6001. PMID: 11698479, ISSN: 0022-1767.

Mora AL, Stanley S, Armistead W, Chan AC, Boothby M. Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kappaB/Rel. J. Immunol. 2001 Nov 11/15/2001; 167(10): 5628-35. PMID: 11698434, ISSN: 0022-1767.

Boothby M. Specificity of sn50 for NF-kappa B? [letter]. Nat. Immunol. 2001 Jun; 2(6): 471-2. PMID: 11376325, PII: 88652, DOI: 10.1038/88652, ISSN: 1529-2908.

Chen Y, Rosloniec E, Goral MI, Boothby M, Chen J. Redirection of T cell effector function in vivo and enhanced collagen-induced arthritis mediated by an IL-2R beta/IL-4R alpha chimeric cytokine receptor transgene. J. Immunol. 2001 Mar 3/15/2001; 166(6): 4163-9. PMID: 11238667, ISSN: 0022-1767.

Mora A, Youn J, Keegan A, Boothby M. NF-kappa B/Rel participation in the lymphokine-dependent proliferation of T lymphoid cells. J. Immunol. 2001 Feb 2/15/2001; 166(4): 2218-27. PMID: 11160275, ISSN: 0022-1767.

Boothby M, Mora AL, Stephenson LM. Lymphokine-dependent proliferation of T-lymphoid cells: regulated responsiveness and role in vivo. Crit. Rev. Immunol. 2001; 21(6): 487-522. PMID: 12058862, ISSN: 1040-8401.

Boothby M, Mora AL, Aronica MA, Youn J, Sheller JR, Goenka S, Stephenson L. IL-4 signaling, gene transcription regulation, and the control of effector T cells. Immunol. Res. 2001; 23(2-3): 179-91. PMID: 11444383, PII: IR:23:2-3:179, DOI: 10.1385/IR:23:2-3:179, ISSN: 0257-277X.

Aronica MA, Goenka S, Boothby M. IL-4-dependent induction of BCL-2 and BCL-X(L)IN activated T lymphocytes through a STAT6- and pi 3-kinase-independent pathway. Cytokine. 2000 Jun; 12(6): 578-87. PMID: 10843732, PII: S1043-4666(99)90603-8, DOI: 10.1006/cyto.1999.0603, ISSN: 1043-4666.

Powell WC, Fingleton B, Wilson CL, Boothby M, Matrisian LM. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Curr. Biol. 1999 Dec 12/16/1999; 9(24): 1441-7. PMID: 10607586, PII: S0960-9822(00)80113-X, ISSN: 0960-9822.

Aronica MA, Mora AL, Mitchell DB, Finn PW, Johnson JE, Sheller JR, Boothby MR. Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo. J. Immunol. 1999 Nov 11/1/1999; 163(9): 5116-24. PMID: 10528218, PII: ji_v163n9p5116, ISSN: 0022-1767.

Goenka S, Youn J, Dzurek LM, Schindler U, Yu-Lee LY, Boothby M. Paired Stat6 C-terminal transcription activation domains required both for inhibition of an IFN-responsive promoter and trans-activation. J. Immunol. 1999 Nov 11/1/1999; 163(9): 4663-72. PMID: 10528163, PII: ji_v163n9p4663, ISSN: 0022-1767.

Mora AL, Chen D, Boothby M, Rubin DH. Lineage-specific differences among CD8+ T cells in their dependence of NF-kappa B/Rel signaling. Eur. J. Immunol. 1999 Sep; 29(9): 2968-80. PMID: 10508271, PII: 10.1002/(SICI)1521-4141(199909)29:09<2968::AID-IMMU2968>3.0.CO;2-X, DOI: 10.1002/(SICI)1521-4141(199909)29:09<2968::AID-IMMU2968>3.0.CO;2-X, ISSN: 0014-2980.

Seetharaman R, Mora AL, Nabozny G, Boothby M, Chen J. Essential role of T cell NF-kappa B activation in collagen-induced arthritis. J. Immunol. 1999 Aug 8/1/1999; 163(3): 1577-83. PMID: 10415062, PII: ji_v163n3p1577, ISSN: 0022-1767.

Aune TM, Mora AL, Kim S, Boothby M, Lichtman AH. Costimulation reverses the defect in IL-2 but not effector cytokine production by T cells with impaired IkappaBalpha degradation. J. Immunol. 1999 May 5/15/1999; 162(10): 5805-12. PMID: 10229814, ISSN: 0022-1767.

Zhang F, Wang DZ, Boothby M, Penix L, Flavell RA, Aune TM. Regulation of the activity of IFN-gamma promoter elements during Th cell differentiation. J. Immunol. 1998 Dec 12/1/1998; 161(11): 6105-12. PMID: 9834094, ISSN: 0022-1767.

Youn J, Chen J, Goenka S, Aronica MA, Mora AL, Correa V, Sheller JR, Boothby M. In vivo function of an interleukin 2 receptor beta chain (IL-2Rbeta)/IL-4Ralpha cytokine receptor chimera potentiates allergic airway disease. J. Exp. Med. 1998 Nov 11/16/1998; 188(10): 1803-16. PMID: 9815258, PMCID: PMC2212401, ISSN: 0022-1007.

Lee SY, Kaufman DR, Mora AL, Santana A, Boothby M, Choi Y. Stimulus-dependent synergism of the antiapoptotic tumor necrosis factor receptor-associated factor 2 (TRAF2) and nuclear factor kappaB pathways. J. Exp. Med. 1998 Oct 10/5/1998; 188(7): 1381-4. PMID: 9763618, PMCID: PMC2212489, ISSN: 0022-1007.

Wang D, Zamorano J, Keegan AD, Boothby M. HMG-I(Y) phosphorylation status as a nuclear target regulated through insulin receptor substrate-1 and the I4R motif of the interleukin-4 receptor. J. Biol. Chem. 1997 Oct 10/3/1997; 272(40): 25083-90. PMID: 9312117, ISSN: 0021-9258.

Boothby MR, Mora AL, Scherer DC, Brockman JA, Ballard DW. Perturbation of the T lymphocyte lineage in transgenic mice expressing a constitutive repressor of nuclear factor (NF)-kappaB. J. Exp. Med. 1997 Jun 6/2/1997; 185(11): 1897-907. PMID: 9166419, PMCID: PMC2196335, ISSN: 0022-1007.

Kovalik JP, Ansari B, Boothby M. Rapid commitment to negative selection of a thymocyte line independent of CD4 co-engagement. J. Immunol. 1996 Dec 12/15/1996; 157(12): 5290-9. PMID: 8955175, ISSN: 0022-1767.

Wang DZ, Cherrington A, Famakin-Mosuro B, Boothby M. Independent pathways for de-repression of the mouse Ig heavy chain germ-line epsilon promoter: an IL-4 NAF/NF-IL-4 site as a context-dependent negative element. Int. Immunol. 1996 Jul; 8(7): 977-89. PMID: 8757943, ISSN: 0953-8178.

Wang DZ, Ray P, Boothby M. Interleukin 4-inducible phosphorylation of HMG-I(Y) is inhibited by rapamycin. J. Biol. Chem. 1995 Sep 9/29/1995; 270(39): 22924-32. PMID: 7559428, ISSN: 0021-9258.

Kim J, Reeves R, Rothman P, Boothby M. The non-histone chromosomal protein HMG-I(Y) contributes to repression of the immunoglobulin heavy chain germ-line epsilon RNA promoter. Eur. J. Immunol. 1995 Mar; 25(3): 798-808. PMID: 7705411, DOI: 10.1002/eji.1830250326, ISSN: 0014-2980.

Whitley MZ, Cheng HL, Tomasi TB, Boothby M. Distinct IL-4 response mechanisms of the MHC gene A alpha in different mouse B cell lines. Mol. Immunol. 1993 Jun; 30(9): 821-32. PMID: 8321247, ISSN: 0161-5890.

Casey LS, Lichtman AH, Boothby M. IL-4 induces IL-2 receptor p75 beta-chain gene expression and IL-2-dependent proliferation in mouse T lymphocytes. J. Immunol. 1992 Jun 6/1/1992; 148(11): 3418-26. PMID: 1588041, ISSN: 0022-1767.

Rothman P, Li SC, Gorham B, Glimcher L, Alt F, Boothby M. Identification of a conserved lipopolysaccharide-plus-interleukin-4-responsive element located at the promoter of germ line epsilon transcripts. Mol. Cell. Biol. 1991 Nov; 11(11): 5551-61. PMID: 1922063, PMCID: PMC361925, ISSN: 0270-7306.

Gravallese EM, Darling JM, Glimcher LH, Boothby M. Role of lipopolysaccharide and IL-4 in control of transcription of the class II A alpha gene. J. Immunol. 1991 Oct 10/1/1991; 147(7): 2377-83. PMID: 1918969, ISSN: 0022-1767.

Whitley MZ, Sisk R, Ivashkiv LB, Finn PW, Glimcher LH, Boothby MR. Non-consensus DNA sequences function in a cell-type-specific enhancer of the mouse class II MHC gene A alpha. Int. Immunol. 1991 Sep; 3(9): 877-88. PMID: 1931814, ISSN: 0953-8178.

Li SC, Rothman P, Boothby M, Ferrier P, Glimcher L, Alt FW. Control of immunoglobulin heavy chain constant region gene expression. Adv. Exp. Med. Biol. 1991; 292: 245-51. PMID: 1950776, ISSN: 0065-2598.

Finn PW, Kara CJ, Van TT, Douhan J, Boothby MR, Glimcher LH. The presence of a DNA binding complex correlates with E beta class II MHC gene expression. EMBO J. 1990 May; 9(5): 1543-9. PMID: 2328725, PMCID: PMC551848, ISSN: 0261-4189.

Liou HC, Boothby MR, Finn PW, Davidon R, Nabavi N, Zeleznik-Le NJ, Ting JP, Glimcher LH. A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. Science. 1990 Mar 3/30/1990; 247(4950): 1581-4. PMID: 2321018, ISSN: 0036-8075.

Boothby M, Liou HC, Finn PW, Gravallese E, Glimcher LH. Control of transcription at the murine A alpha locus. Immunol. Res. 1990; 9(2): 77-92. PMID: 2189937, ISSN: 0257-277X.

Gravallese EM, Boothby MR, Smas CM, Glimcher LH. A lipopolysaccharide-induced DNA-binding protein for a class II gene in B cells is distinct from NF-kappa B. Mol. Cell. Biol. 1989 Aug; 9(8): 3184-92. PMID: 2477682, PMCID: PMC362362, ISSN: 0270-7306.

Boothby M, Liou HC, Glimcher LH. Differences in DNA sequence specificity among MHC class II X box binding proteins. J. Immunol. 1989 Feb 2/1/1989; 142(3): 1005-14. PMID: 2492326, ISSN: 0022-1767.

Boothby M, Gravallese E, Liou HC, Glimcher LH. A DNA binding protein regulated by IL-4 and by differentiation in B cells. Science. 1988 Dec 12/16/1988; 242(4885): 1559-62. PMID: 3144043, ISSN: 0036-8075.

Liou HC, Boothby MR, Glimcher LH. Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element. Science. 1988 Oct 10/7/1988; 242(4875): 69-71. PMID: 3140376, ISSN: 0036-8075.

Boime I, Boothby M, Darnell RB, Policastro P. Structure and expression of human placental hormone genes. Adv. Exp. Med. Biol. 1986; 205: 267-80. PMID: 3788716, ISSN: 0065-2598.

Hoshina M, Boothby M, Hussa R, Pattillo R, Camel HM, Boime I. Linkage of human chorionic gonadotrophin and placental lactogen biosynthesis to trophoblast differentiation and tumorigenesis. Placenta. 1985 Mar; 6(2): 163-72. PMID: 2991878, ISSN: 0143-4004.

Hoshina M, Boothby MR, Hussa RD, Pattillo RA, Camel HM, Boime I. Segregation patterns of polymorphic restriction sites of the gene encoding the alpha subunit of human chorionic gonadotropin in trophoblastic disease. Proc. Natl. Acad. Sci. U.S.A. 1984 Apr; 81(8): 2504-7. PMID: 6201859, PMCID: PMC345090, ISSN: 0027-8424.

Policastro P, Ovitt CE, Hoshina M, Fukuoka H, Boothby MR, Boime I. The beta subunit of human chorionic gonadotropin is encoded by multiple genes. J. Biol. Chem. 1983 Oct 10/10/1983; 258(19): 11492-9. PMID: 6194155, ISSN: 0021-9258.

Boothby M, Kukowska J, Boime I. Imbalanced synthesis of human choriogonadotropin alpha and beta subunits reflects the steady state levels of the corresponding mRNAs. J. Biol. Chem. 1983 Aug 8/10/1983; 258(15): 9250-3. PMID: 6192128, ISSN: 0021-9258.

Hoshina M, Boothby M, Boime I. Cytological localization of chorionic gonadotropin alpha and placental lactogen mRNAs during development of the human placenta. J. Cell Biol. 1982 Apr; 93(1): 190-8. PMID: 6896058, PMCID: PMC2112094, ISSN: 0021-9525.

Boime I, Boothby M, Hoshina M, Daniels-McQueen S, Darnell R. Expression and structures of human placental hormone genes as a function of placental development. Biol. Reprod. 1982 Feb; 26(1): 73-91. PMID: 6279188, ISSN: 0006-3363.

Boothby M, Ruddon RW, Anderson C, McWilliams D, Boime I. A single gonadotropin alpha-subunit gene in normal tissue and tumor-derived cell lines. J. Biol. Chem. 1981 May 5/25/1981; 256(10): 5121-7. PMID: 6262319, ISSN: 0021-9258.

Kohler PO, Riser M, Hardin J, Boothby M, Boime I, Norris J, Siciliano MJ. Chorionic gonadotropin synthesis and gene assignment in human:mouse hybrid cells. Adv. Exp. Med. Biol. 1981; 138: 405-18. PMID: 7342721, ISSN: 0065-2598.

Available Postdoctoral Position Details
Posted: 1/26/2015
Molecular immunology. (1) dissect the regulation of gene expression in T lymphocytes, and the acquisition and maintenance of functional characterisitics of helper
T cells in vitro and in the intact animal; current foci:
(a) a newly cloned, novel protein collaborating with the allergy-related transcription factor Stat6, and
(b) NF-kappaB and chromatin. (2) investigate cytokine receptor signaling mechanisms in regulating the acquisition and maintenance of functional characterisitics of helper T cells in vitro and in the intact animal.