ࡱ>  hbjbj )`m;H H     8U:hp" "7$7$7$7$7$7$7{<?~$7 $7#5  9#5#5#5,  "7#5"7#5#5V,6@  6oyXP,,l6 6D90:x6 ?#5?6#56> 6H :   CURRICULUM VITAE June 22, 2012 Name: Mark Robin Boothby Home address: 2104 Twentieth Ave South, Nashville, TN 37212 Work address: AA-4214 MCN, Dept. of Pathology, Microbiology & Immunology, VanderbiltUniversity Medical School, Nashville, TN 37232-2363 Contact: 615-343-1699 E-mail: mark.boothby@vanderbilt.edu Date of birth: August 16, 1955 Place of birth: Evanston, IL USA Education: 1976 B.S. University of Wisconsin, Madison, WI 1983 M.D. Washington University School of Medicine, 1983 Ph.D. St. Louis, MO (Molecular Biology) Postdoctoral training: Internship and residencies: 1983-1984 Intern in Medicine, the University of Colorado 1984-1986 Resident in Medicine, the University of Colorado, Denver CO Fellowships: 1986-1988 Research fellow, Harvard Medical School 1986-1989 Clinical fellow, Rheumatology, Brigham and Women's Hospital, Boston MA 1986-1988 Postdoctoral fellow, Department of Cancer Biology, Harvard School of Public Health, Boston MA 1989 Research Associate, Department of Cancer Biology, Harvard School of Public Health, Boston MA Licensure and Certification: 1984 Colorado License Registration 1986 Diplomate, American Board of Internal Medicine 1989 Rheumatology Subspecialty Certification, American Board of Internal Medicine 1989-1992 Massachusetts License Registration 1992- Tennessee License Registration Academic Appointments: 1988-1989 Instructor in Medicine, Harvard Medical School, Boston, MA 1990-1992 Assistant Professor of Immunology, Harvard School of Public Health, Boston, MA 1990-1992 Assistant Professor of Medicine, Harvard Medical School 1992-1997 Assistant Professor, Dept of Microbiology and Immunology, Vanderbilt University, Nashville, TN (primary appointment) 1992-2000 Assistant Professor of Medicine, Vanderbilt University (VU). 1998-2005 Associate Professor (tenured), Dept. Microbiology and Immunology, Vanderbilt University, Nashville, TN (primary appointment) 2000-2006 Associate Professor, Dept. of Medicine (Rheumatology), VU 2005- present Professor (tenured), Dept. Microbiology & Immunology Vanderbilt University School of Medicine 2006- present Professor, Dept. of Medicine (Rheumatology), VUSM 2011-present Professor (tenured), Dept. Pathology, Microbiology & Immunology Hospital Appointments: 1989-1992 Associate Rheumatologist, Brigham & Women's Hospital, Boston, MA 1992-2005 Part-time Medical Staff, Vanderbilt Univ. Hospital, Nashville, TN Awards and Honors: 1976 Phi Beta Kappa 1976 National Science Foundation Graduate Fellowship (declined) 1983 Alpha Omega Alpha 1989 Hilda Duggan Arthritis Investigator Award, Arthritis Foundation 1989 Special Fellow Award, Leukemia Society of America (declined) 1992 Special Fellow Award, Leukemia Society of America 1992 Baxter Scholar in Immunology, Baxter Foundation 1995 Leukemia Society of America Scholar Award 2001 Senior Investigator Award, American Asthma Foundation (formerly Sandler Program for Asthma Research) 2006 Faculty of 1000 2011 Ernest Goodpasture Award for Research (VUSM) Professional Societies: 1989 American Association for the Advancement of Science 1990 American Association of Immunologists 1994 Int'l Assoc. for Comparative Res. on Leukemia and Related Diseases National service - peer review experience (ad hoc): Grants: Association for International Cancer Research Human Frontiers Program Leukemia & Lymphoma Society of America National Science Foundation Scleroderma Foundation VAMC, Merit Review Journals: Arthritis and Rheumatism Blood Cancer Research EMBO Journal Genes & Development Immunity International Immunology Journal of Biological Chemistry Journal of Clinical Investigation Journal of Experimental Medicine Journal of Immunology Molecular and Cellular Biology Nature Immunology New England Journal of Medicine Oncogene Proceedings of the National Academy of Sciences USA Respiratory Research National & international service: meetings, peer review panels, committees, & Boards: 1990 Chair, MHC regulation minisymposium, FASEB 1995 Co-chair, T cell development minisymposium, FASEB '95 1996-1998 Molecular Immunology Study Section, national Arthritis Foundation 1998 Chair, IL-4 regulation and signaling Block symposium, FASEB '98 1999 NIH CSR, ALY Study Section (ad hoc) 2000 NIH / NIAID SEP, Costimulation & Autoimmunity PPG. 2001 Co-chair, AAI Symposium on Signaling, Exptl Biology 2001 2001-2004 Finance Committee, American Assoc. Immunologists (AAI) 2002 NIH CSR, ALY Study Section (ad hoc) 2002 NIH CSR, Special Study Section 2002 NIH CSR, IMB Study Section (ad hoc) 2004 NIH / NIAID Special Emphasis Panel, co-Chair, "Immune System Development and the Origins of Asthma" 2004 NIH / CSR Special Emphasis Panel 2004 NIH / CSR CMI-A Study Section (ad hoc) (06/04) 2004 NIH / CSR CMI-A Study Section (ad hoc) (10/04) 2004-2007 Finance Committee, American Assoc. Immunologists (AAI) 2005-2010 Board of Directors, Federation of American Societies for Experimental Biology (FASEB) 2006 Leukemia & Lymphoma Society of America (LLS), national Career Development Program review committee 2006 NIH / CSR CMI-A Study Section (ad hoc) 2007-present Leukemia & Lymphoma Society of America (LLS), national Career Development Program review committee 2007-2010 Chair, NIH Issues Subcommittee, FASEB Science Policy Committee 2008-present Charter membership, NIH CSR, CMI-B study section 2010 Program committee, PARP2010 meeting (Zurich, CH) Invited presentations: 1991 University of Florida, Division of Rheumatology, Gainesville, FL 1992 Massachusetts General Hospital, Mucosal Immunity seminars,Boston, MA 1992 University of Washington, Dept. Immunology, Seattle, WA 1992 University of Cinncinnati & Children's Hospital Medical Center 1994 Abbott Laboratories, Abbott Park, IL. 1995 Experimental Biology '95 meeting, Atlanta, GA 1996 Institute for Human Gene Therapy,University of Pennsylvania 1996 Virginia Mason Research Center, Seattle, WA 1996 U Conn Health Science Center, Div. Rheumatic Diseases, Farmington, CT 1996 San Francisco VA Med Ctr / UCSF, Div. of Rheumatology 1997 Division of Inflammatory Diseases, Boehringer-Ingelheim, Ridgefield, CT 1999 Laboratory of Immunology, NIAID, NIH, Bethesda, MD 1999 Holland Lab, American Red Cross, Rockville, MD 2000 University of Rochester, Rochester, NY 2000 University of Vermont Medical School, Burlington, VT 2000 Immunology Council, Johns Hopkins School of Medicine, Baltimore, MD 2001 Immunology Colloquium, University of Pennsylvania, Philadelphia, PA 2001 Rheumatology Divisional Conference, Tufts / NEMC, Boston, MA 2001 Departmental Seminar series, Medical College of Georgia, Augusta GA 2001 Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, Nice, FR 2002 University of Chicago, Immunology Seminar Serie, Chicago IL 2004 Keystone Symposium on NF-kappaB, Snowbird, UT 2004 CSH Symposium, Gene Expression & Signaling in the Immune System 2004 Tennessee State University (MARC seminar series) 2005 University of Maryland - Dover (MARC seminar series) 2005 Center for Biotechnology, University of Turku (Turku, Finland) 2005 Pennsylvania State University, State College, PA 2005 La Jolla Institute of Allergy & Immunology, La Jolla, CA 2006 University of Iowa, Iowa City, IA 2009 City of Hope Seminar Series, Duarte, CA 2010 Duke University, Immunology Seminar Series, Durham NC 2010 Keystone Symposium on Lymphocyte Activation and Signaling Breckenridge CO 2010 National Institute on Aging, Baltimore MD 2011 UC-Riverside Medical School, Riverside, CA 2011 Keystone Symposium on Immunologic Memory, Persisting Microbes, & Chronic Diseases, Banff, Alberta (Canada) 2011 6th Annual International Conference on Signaling in Leukocytes, Chania, Crete (Greece) 2012 Keystone Symposium on Signaling Regulation in Lymphocytes 2012 St. Jude Medical Center, Dept. of Immunology, Memphis, TN 2012 Genentech, Inc., South San Francisco, CA 2012 National Institute on Aging, Baltimore, MD pending / booked 2012 Roswell Park Cancer Institute, Buffalo, NY 2013 U. Texas MD Anderson Cancer Center, Houston, TX Trainees: Predoctoral: 1989-1991 Maryann Whitley (D.Sc. thesis advisor; AHA post-doctoral fellow, Dept. Pathology, Brigham and Women's, Boston; currently Research Scientist, Genetics Institute, Boston, MA) 1992 Alex Dranovsky (M.D., Ph.D, SUNY Stonybrook; currently Assistant Professor, Psychiatry / Neuroscience fellow, Columbia University, NY (K08 & now R01 awardee as PI) 1996-1999 Sarah Stanley (completed Ph.D., UCSF; post-doc @ Broad Inst. & MIT) 1999-2004 Linda ('Lynn') Stephenson (nee Dzurek) (VUMC Ph.D. student) Research Scientist, Sigma-Aldrich, St Louis, MO, after a post-doctoral fellowship, Dept. of Pathology, Washington University Medical School, St. Louis MO 2001-2005 Radiah Corn (Meharry Medical College Ph.D. student) Assistant Professor, North Carolina after a post-doctoral fellowship, NIEHS, Research Triangle, NC 2006- Christopher L. Williams Post-doctoral: 1989-1990 Leslie Casey, Ph.D. (Senior Scientist, Cistron Biotechnology, Pine Brook NJ; currently Senior Director of Research, Elusys, Inc) 1992-1997 Ding-Zhi Wang, Ph.D. (currently Professor, Dept. Cancer Biol., MD Anderson Cancer Center, Houston, TX) 1994-1995 Bijan Ansari, M.D., Ph.D. (last known position - Asst. Professor of Pathology, Zanjan University, Iran) 1995-2002 Mark Aronica, M.D. (Asst. Professor equivalent, Depts. of Medicine, Immunology, Lerner Res. Inst., Cleveland Clinic Foundation) (K08 & now R01 awardee as PI) 1995-2002 Ana L Mora, M.D. (Asst. Professor, Dept. Medicine, Emory University, now at U. Pittsburgh M.C.) (K01 awardee) 1996-1998 Jeehee Youn, Ph.D. (Assoc. Professor, Dept. of Anatomy/Cell Biology, Hanyang University Medical School., Seoul, Korea) 1997- 2004 Shreevrat Goenka, Ph.D. (Assistant Professor, University of Indiana School of Medicine, Indianapolis, IN) (R01 awardee as PI) 2001- 2007 Eric Adeeku, Ph.D. (staff Microbiologist, US Food & Drug Administration, Rockville, MD) 2001- 2004 Yanhong Zhang, Ph.D. (to Zutter lab, Dept. Pathol., VUSM) 2001- 2006 Fuping Zhang, Ph.D. (@ Strober lab, NIAID) 2005-present Sung Hoon Cho, Ph.D. 2005-2008 Ross M. Potter, Ph.D. (@ present, 2nd post-doc @ Mayo Scottsdale) 2006-present Keunwook Lee, Ph.D. 2010-present Marcia Schilling, Ph.D. Visiting Faculty & Visiting Scientists: 1996-1998 Atsushi Karashima, M.D., Ph.D. (Visiting Scholar; now at Dept. of Neurosurgery, Oita Medical School, Oita, Japan). 1998 Victor Arrunategui-Correa, Ph.D. (visiting scientist) 2004- 2006 Do Sim Park, M.D. (Visiting Asst. Professor) Institutional Committee Work: 1991- 1992 Course Coordination Committee, HSPH 1992- 1994 Immunology Steering Committee, VUMC 1992- 1995 Goodpasture Professorship Search Committee, VUMC 1995- 1996 Leukemia / Lymphoma Search Committee, VU Cancer Center 1998 LCME Institutional Self-Evaluation; Subcommittee on Resources for the Educational Mission: Faculty 1999 VUMC Discovery Grant review panel 1999 - present Medical Scientist Training Program Advisory Committee 1999 VUMC Discovery Grant Review Committee 2000 - present CBMS Training Grant Advisory Committee 2001 - 2003 Faculty Advisory Council, VU School of Medicine 1992 - present Qualifying Exam and Thesis Advisory Committees current roster: C. L. Williams (my lab), J. Williams, A. Melo, P. Wagner (CDB); K. Amato (pending) selected past: L. Gordy, Srdjan Dragovic, E. Johnson, M. Vetter, C. Gabriel; K. McCall, N. Shinners, V. Gerbasi, E. Woodward, Z. Liu, A. Stanic, J. Bezbradica; M. Schilling (MPB), J. Stafford (Biochem), L. Yang (Cancer Biol.), J. Ohm (Cancer Biol.) 2005 - 2007 Search Committee (Immunology Faculty / Dept. Micro & Immunol.) 2007 - 2008 Co-chair, Committee on Measuring Progress (Basic Science update, Strategic Academic Planning process) Teaching Experience: 1989 - 1991 Lecturer, Immunology 204, Graduate School of Arts and Sciences, Harvard Medical School 1989 - 1992 Presented new lecture series, Topics in Basic Immunology, Departments of Rheumatology/Immunology (BWH), Medicine (HMS) 1990 Bio 91r (supervised reading), Harvard College 1991 -1992 Division of Biological Sciences, DBS 210, Molecular Mechanisms of Immune Regulation (developed new course) 1993 - 2001 Lecture series, Immunology section, VMS I 1993 - 1994 Immunology Lecture sections, VUMC Interdisciplinary Graduate Program 1993- present Flextime sections, Immunology component, VUMC IGP 1993 - 1994 Course director, Graduate Immunology, Vanderbilt University 1994 Physical Diagnosis: Rheumatic Diseases, VMS II 1994 - 1995 Co-director and Preceptor, Microbial Topics, VMS I Microbiology & Immunology 1994 - present Course faculty, Graduate ("Molecular & Cellular") Immunology 1995 - 2009 Preceptor, Microbial Topics, (Coordinator through 2004) VMS I Microbiology & Immunology 1999 - present Coordinator and Preceptor: Foundations of Immunology (M&IMM334) 2000 - present Preceptor and Co-director, MSTP Seminar course 2002 - present Coordinator, Immunology component of Dept. seminar series Major Research Interest: Molecular programming of lymphocytes in immune responses: mechanisms of IL-4 action on lymphocytes; mechanisms regulating effector function in T lymphocytes -- activation, differentiation, apoptosis, & memory. Molecular pathogenesis in allergic diseases Grant Support: Past: 1989-1992 Arthritis Investigator Award 1989-1994 N.I.H. R29 GM42550 (F.I.R.S.T. Award) 1992-1995 Leukemia Society of America Special Fellow Award 1992-1995 Baxter Foundation Scholars Award. 1995-1999 Interleukin 4 regulation of lymphocyte gene expression. NIH R01 GM42550 1995-1999 Thymocyte activation and apoptosis: genetic analysis. NIH R01AI36997 1995-2000 Leukemia Society of America Scholar Award Thymocyte activation and apoptosis 1997-2000 Mouse models to investigate role in T cells of signaling by TNF-R superfamily members. Boehringer-Ingelheim Pharmaceuticals (total costs $42,000) 1998-1999 Immune Deviation and Diabetes: Effect of a chimeric IL2/4 receptor transgene NIH P60 DK 20593 (Diabetes Research & Training Center Pilot Project) 1999-2000 Interleukin 4 regulation of lymphocytes NIH R 01 GM42550-10S1 (direct costs $45,000) 2001 VUMC Discovery Grant: Pilot Project TCR signaling & NF-kB: Molecular regulation & proteomics annual direct costs $25,000 2001-2002 Transcriptional regulation of the type 1 T cell response NIH R21 AI49460-01 (bridge award; $225,000 direct costs) 1998-2002 Allergic airway responses: Immune deviation and memory NIH R01 HL-61752 (year 04 direct costs ca. $185,000) 2001-2004 Memory regulation and allergic airways disease Sandler Program for Asthma Research (annual total costs $250,000) 2000-2005 Interleukin 4 regulation of lymphocytes NIH R 01 GM42550-14S1 (bridging direct costs ca. $73,000) 2001-2006 Program Project: Functional Genomics of Inflammation NIH P01 HL68744 (P.I.- Jack J. Hawiger, M.D., Ph.D.) Project 3: T-Lymphocyte-Based Functional Genomics of Inflammation (Van Kaer - Leader; co-investigator, 5% effort) 2006-2008 Epitope Discovery via Nanocluster Presentation NIH 1 R01 GM076479-01 (co-investigator, 3% effort) P.I. - David Cliffel, Ph.D, Dept of Chemistry 2002-2006 Transcriptional regulation of the type 1 T cell response NIH R01 AI49460-04 (modular annual direct costs $225,000) (no-cost extensions 2/1/06-1/31/09) 2007-2008 Role of mTOR complex 2 in T cell leukemia and Notch-induced cancer Pilot Project, VICC Cancer Center grant (one year award of $35,000) 2004-2008 Integration of Stat6, coregulation, and gene expression NIH R01 GM071735-04 (modular annual direct costs, $200,000, reduced to ~$186,000 with NIH cuts; no-cost extensions 7/1/2008-6/30/2010) 2006-2011 Interleukin 4 regulation of lymphocytes NIH 2 R01 AI068149-19 (No-cost Extension 2011-2012) CURRENT: 2009-2014 Flexibility and commitment in post-effector CD4 lymphocytes NIH 1 R01 AI077528-02 (modular annual direct costs $250,000) 2010-2014 Impact of IKKB and AurK Inhibitors on Host Immunity and Melanoma NIH 1 R01 CA116021-08 (PI - Richmond, Ann W.) 2011-2014 Roles of rictor in mTOR signaling, differentiation & immune memory via Akt and PKC NIH 1 R01 HL106812-01 (modular annual direct costs $250,000; 1/15/2011 11/30/2014 <4 yr>) 2011-2016 Epithelial IL4Ralpha Regulates Colon Tumor Progression NIH 1 R01 CA157781-02 (PI - Fingleton, Barbara F.) pending: 2012-2014 NIH / NCI R21 application, Provocative Questions in Cancer (dual PI application with J. Chen, M.D., Ph.D. in planning or preparation: (timing & titles are tentative) 2013-2018 Regulation of recall antibody responses by IL-4, STAT6, & their affiliated mART NIH 1 R01 2013-2018 Regulation of B lineage fate choices and antibody production by mTOR. BIBLIOGRAPHY: Original reports: 1. Stahl PD, Boothby M, Owens JW, Gammon K. 1974. Studies with rat liver microsomal - glucuronidase. Methodological Devel. Biochem. 14: 271-279. 2. Boothby M, Daniels-McQueen S, McWilliams D, Zernik M, Boime I. 1980. Human chorionic gonadotropin alpha and beta subunit mRNAs: Translatable levels during pregnancy and molecular cloning of sequences complementary to hCG. In: Segal S., ed. Chorionic Gonadotropin. New York: Plenum Press, 253-275 (original report of hCGa and hCGb cDNA cloning; appeared in symposium volume). 3. Boothby M, Ruddon RW, Anderson C, McWilliams D, Boime I. 1981. A single gonadotropin alpha subunit gene in normal tissue and tumor-derived cell lines. J Biol Chem. 256: 2151-2157. 4. Hoshina M, Boothby M, Boime I. 1982. Cytological localization of choriogonadotropin alpha and placental lactogen mRNAs during development of the human placenta. J Cell Biol. 93: 190-198. 5. Boothby M, Kukowska J, Boime I. 1983. Polysomal synthesis of human chorionic gonadotropin alpha and beta subunits is imbalanced and reflects imbalanced mRNA levels. J Biol Chem. 258: 9250-9253. 6. Policastro P, Ovitt C, Hoshina M, Fukuoka H, Boothby M, Boime I. 1983. The beta subunit of human chorionic gonadotropin is encoded by multiple genes. J Biol Chem. 258:11492-11499. 7. Hoshina M, Boothby M, Hussa R, Pattillo R, Camel M, Boime I. 1984. Segregation patterns of polymorphic restriction sites of the gene encoding the alpha subunit of human chorionic gonadotropin in trophoblastic disease. Proc Nat'l Acad Sci USA. 81: 2504-2507. 8. Liou H-C, Boothby M, Glimcher LH. 1988. Distinct cloned class II MHC DNA-binding proteins recognize the X box transcription element. Science 242: 69-71. 9. Boothby M, Gravallese E, Liou H-C, Glimcher LH. 1988. A DNA-binding protein regulated by IL-4 and by differentiation in B cells. Science 242: 1559-1562. 10. Boothby, M., Liou H-C, Glimcher LH. 1989. Differences in DNA sequence specificity among MHC Class II X box binding proteins. J. Immunol. 142: 1005-1014. continued 11. Gravallese E, Boothby M, Smas C, Glimcher LH. 1989. A lipopolysaccharide-induced DNA binding protein in B cells is distinct from NF-kB. Mol. Cell Biol. 9: 3184-3192. 12. Liou HC, Boothby M, Finn PW, Davidon R, Nabavi N, Zeleznik-Le NJ, Ting JP-Y, Glimcher LH. 1990. A new member of the leucine zipper class of proteins which binds to the HLA DRA promoter. Science 247: 1581-1584. 13. Finn PW, Kara CJ, Van TT, Douhan J III, Boothby M, Glimcher LH. 1990. The presence of a DNA-binding complex correlates with Eb class II gene expression. EMBO Journal 9: 1543-1549. Faculty era papers 14. Whitley MZ, Sisk R, Ivashkiv L, Finn PW, Glimcher LH, Boothby M. 1991. Non-consensus DNA sequences function in a cell-type specific enhancer of the class II MHC gene Aa. International Immunology 3: 877-888. 15. Gravallese E, Darling J, Glimcher LH, Boothby M. 1991. Relationship of LPS and IL-4 in control of transcription of the murine class II MHC Aa gene. J. Immunol. 147: 2377-2383. 16. Rothman P, Li S, Gorham B, Glimcher LH, Alt F, Boothby M. 1991. Identification of a Conserved IL-4 /LPS Responsive Element Located at the Promoter of Germline e Transcripts. Mol. Cell Biol. 11: 5551-5561. 17. Casey LS, Lichtman AH, Boothby M. 1992. IL-4 induces IL-2 receptor p75 b chain gene gene expression, and IL-2 dependent proliferation in mouse T lymphocytes. J. Immunol. 148: 3418-3426. 18. Whitley MZ, Cheng H-W, Tomasi TB, Boothby M. 1993. Distinct IL-4 response mechanisms of the MHC gene Aa in different mouse B cell lines. Molec. Immunol. 30: 821-832. 19. Kim J, Reeves R, Rothman P, Boothby M. 1995. The non-histone chromosomal protein HMG-I(Y) contributes to repression of the immunoglobulin heavy chain germline epsilon promoter. Eur. J. Immunol. 25, 788-798. 20. Wang D-Z, Ray P, and Boothby M. 1995. Rapamycin inhibits interleukin 4-inducible phosphorylation of HMG-I(Y). J. Biol. Chem. 270, 22924-22932. 21. Wang D-Z, Cherrington AL, Famakin-Mosuro BM, and Boothby M. 1996. Independent pathways to de-repression of the mouse immunoglobulin heavy chain epsilon germ-line promoter. Int'l Immunol. 8: 977-989. 22. Kovalik J-P, Ansari B, and Boothby M. 1996. Rapid commitment to negative selection of a thymocyte line independent of CD4 co-engagement. J. Immunol. 157: 5290-5299. 23. Boothby M., Mora AL, Scherer DC, Brockman J, and Ballard DW. 1997. Perturbation of the T lymphocyte lineage in transgenic mice expressing a constitutive repressor of NF-kB. J. Exp. Med. 185: 1897-1907. 24. Wang DZ, Zamorano J, Keegan A, and Boothby M. 1997. HMG-I(Y) phosphorylation status as a nuclear target regulated through the I4R motif of the IL-4 receptor. J. Biol. Chem. 272: 25083-25090. 25. Lee SY, Kaufman DR, Mora AL, Santana A, Boothby M, and Choi Y. 1998. Stimulus-dependent synergism of the anti-apoptotic TRAF2 and NF-kB pathways. J. Exp. Med. 188: 1381-1384. 26. Zhang F, Wang DZ, Boothby M, Penix LA, and Flavell RA, Aune TM. 1998. Regulation of the activity of IFN-g promoter elements during T helper cell differentiation. J. Immunol. 161: 6105-6112. continued 27. Youn J, Chen J, Goenka S, Aronica MA, Mora AL, Correa V, Sheller JR, and Boothby M. 1998. In vivo function of an IL-2Rb / IL-4Ra cytokine receptor chimera potentiates allergic airway disease. J. Exp. Med. 188: 1803-1816. 28. Aune TM, Mora AL, Kim S, Boothby M*, and Lichtman AH. 1999. Costimulation reverses the defect in IL-2 but not effector cytokine production by T cells with impaired IkBa degradation. J. Immunol. 162:5805-5812. (* corresponding author) 29. Seetharaman R, Mora A, Nabozny G, Boothby M, and Chen J. 1999. Essential role of T cell NF-kB activation in collagen-induced arthritis. J. Immunol. 163: 1577-1583. 30. Mora AL, Chen D., Boothby M, Rubin D. 1999. Lineage-specific differences among CD8+ T cells in their dependence on NF-kB/Rel signaling. Eur. J. Immunol. 29: 2968-2980. 31. Goenka S, Youn J, Dzurek L, Schindler U, Yu-Lee L-y, Boothby M. 1999. Paired Stat6 C-terminal transcription activation domains required both for inhibition of an interferon-responsive promoter and for trans -activation. J. Immunol. 163: 4663-4672. 32. Aronica MA, Mora AL, Mitchell DB, Johnson JE, Finn PW, Sheller J, and Boothby M. 1999. Preferential role for NF-kB / Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo. J. Immunol. 163: 5116-5124. 33. Powell WC, Fingleton B., Wilson CL, Boothby M, and Matrisian LM. 1999. The metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial cell apoptosis. Current Biol. 9:1441-1447. 34. Aronica MA, Goenka S, Boothby M. 2000. IL-4-dependent induction of Bcl-2 & Bcl-X in T lymphocytes through a Stat6- & PI 3-kinase-independent pathway. Cytokine. 6: 578-87. 35. Mora AL, Youn J, Keegan AD, and Boothby M. 2001. Mechanisms of NF-kB/Rel participation in the lymphokine-dependent proliferation of T lymphoid cells. J. Immunol. 166: 2218-2227. 36. Chen Y, Rosloniec E, Boothby M, and Chen J. 2001. Redirection of T cell effector function in vivo and enhanced collagen-induced arthritis mediated by an IL-2Rb / IL-4Ra chimeric cytokine receptor transgene. J. Immunol. 166, 4163-4169. 37. Zamorano J, Mora AL, Boothby M, and Keegan AD. 2001. NF-kappaB activation plays an important role in the IL-4-induced protection from apoptosis. Int. Immunol. 13: 1479-1487. 38. Mora, AL, Stanley SA, Armistead W, Chan AC, and Boothby M. 2001. Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kB/Rel. J. Immunol. 167: 5628-5635. 39. Finn PW, Stone JR, Boothby MR, Perkins DL. 2001. Inhibition of NF-kappaB-dependent T cell activation abrogates acute allograft rejection. J. Immunol. 167: 5994-6001. 40. Chen Y, Rosloniec E, Price J, Boothby M, and Chen J. 2002. Constitutive expression of Bcl-xL in the T Lineage Attenuates Collagen-Induced Arthritis in Bcl-xL transgenic mice. Arthritis Rheum. 46: 514-521. 41. Haley KJ, Ciota A, Contreras JP, Boothby MR, Perkins DL, and Finn PW. 2002. Alterations in lung collectins in an adaptive allergic immune response. Am. J. Physiol. Lung Cell. Mol. Physiol. 282:L573-84. 42. Harlin H., Hwang KW, Kim O, Thompson CB, Boothby M, and Alegre M-L. 2002. CTLA-4 engagement regulates NF-kB activation in vivo. Eur. J. Immunol. 32:2095-2104. 43. Harlin H, Podack, E, Boothby M, and Alegre M-L. 2002. TCR-independent CD30 signaling selectively induces IL-13 production via a TRAF/p38 MAPK-dependent mechanism. J. Immunol. 169:2451-2460. continued 44. Soutto, M, Zhang F, Enerson B, Tong Y, Boothby M, and Aune T. 2002. A minimal IFN-g promoter confers Th1-selective expression. J. Immunol. 169: 4205-4212. 45. Finn PW, He H, Ma C, Mueller T, Stone JR, Liou HC, Boothby MR, Perkins DL. 2002. Molecular profiling of the role of the NF-kappaB family of transcription factors during alloimmunity. J Leukoc Biol. 72:1054-1062. 46. Zhou P, Hwang KW, Palucki DA, Guo C, Boothby M, Newell K, and Alegre M-L. 2003. Impaired NF-kB activation in T cells permits tolerance induction to fully mismatched skin allografts. Am. J. Transplantation. 3:139-147. 47. Yang, L., Yamagata, N., Yadav, R., Brandon, S., Courtney, R. L., Morrow, J. D., Shyr, Y., Boothby, M., Joyce, S., Carbone, D. P., and Breyer, R. M. 2003. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor J. Clin Invest. 111: 727-735. 48. Mora AL, *Goenka S, *Stanic-Kostic A, *Corn, R, Aronica MA, Stanley S, Ballard DW, Joyce S, and Boothby M. 2003. Anti-apoptotic function of NF-kB in T lymphocytes is influenced by their differentiation status: Roles of Fas, c-FLIP, and Bcl-xL. Cell Death & Differentiation 10:1032-1044. (* co-second authors / equal contributions / name order interchangeable) 49. *Corn R, *Aronica M, Zhang F, Tong Y, Stanley S, Kim SRA, Stephenson LM, Enerson B, McCarthy S, Mora A, and Boothby M. 2003. T cell-intrinsic requirement for NF-kB induction in post-differentiation IFN-g production and clonal expansion in a Th1 response. J. Immunol. 171:1816-1824. (* jointly first authors) 50. Tato CM, Villarino A, Caamano J, Boothby M, and Hunter CA. 2003. Inhibition of NF-kB activity in T can NK cells results in defective effector cell expansion and production of IFN-g required for resistance to Toxoplasma gondii. J. Immunol. 170: 3139-3146. 51. *Mora AL, *Stephenson LM, Enerson B, Youn JH, Keegan AD, and Boothby M. 2003. New programming of IL-4 receptor signal transduction in activated T cells: Stat6 induction and Th2 development promoted by tyrosine-free IL-4Ra. J. Immunol. 171:1891-1900. (* jointly first authors) 52. Goenka S, Marlar C, Schindler U, and Boothby M. 2003. Differential roles of C-terminal activation motifs in the establishment of Stat6 transcriptional specificity. J. Biol. Chem. 278: 50362-50370. 53. Aronica MA, McCarthy S, Mitchell D, Swaidani, S, Goral M, Sheller JR, and Boothby M. 2004. Recall Th2 response: Th1-resistant allergic susceptibility without biasing uncommitted CD4 T cells. Am. J. Resp. Crit. Care Med. 169: 587-595. 54. Stanic AK, Bezbradica JS, Park J-J, Matsuki N, Mora AL, Van Kaer L, Boothby M, and Joyce S. 2004. NF-kB controls cell fate specification, survival, and molecular differentiation of iNKT lymphocytes. J. Immunol. 172: 2265-2273. 55. Stanic, AK, Bezbrakica JS, Van Kaer L, Boothby M, Joyce S. 2004. The ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by PKC-q and NF-kB. Cutting Edge J. Immunol. 172: 4667-4671. 56. Stephenson LM, Mora AL, Woodward E, and Boothby M. 2004. An IL-4Ra allelic variant, I50, acts as a gain-of-function variant relative to V50 for Stat6 but not Th2 differentiation. J. Immunol. 173: 4523-4528. 57. Heller NM, Matsukura S, Georas SN, Boothby MR, Rothman PB, Stellato C, Schleimer RP. 2004. Interferon-gamma inhibits STAT6 signal transduction and gene expression in human airway epithelial cells. Am. J. Respir. Cell. Mol. Biol. 31: 573-582. continued 58. Aronica MA, Swaidani, S, Zhang YH, Mitchell D, Mora AL, McCarthy S, Topham D, Sheller JR, and Boothby M. 2004. Susceptibility to allergic lung disease regulated by recall responses of dual-specificity memory T cells. J. Allergy Clin. Immunol. 114: 1441-1448. 59. Tong Y, Aune TA, Boothby M. 2005. T-bet antagonizes mSin3a recruitment and trans-activates a fully methylated IFN-gamma promoter via a conserved T-box half-site. Proc. Natl. Acad. Sci. USA 102: 2034-2039. 60. Corn RA, Caamano J, Hunter CA, Liou HC, Siebenlist U, and Boothby M. 2005. Opposing roles for RelB and Bcl-3 in regulation of T-bet, GATA-3, and T helper effector differentiation. J. Immunol. 175: 2102-2110. 61. Jones RG, Saibil S, Pun JM, Elford A, Bonnard M, Pellegrini M, Arya S, Parsons M, Krawczyk C, Gerondakis S, Yeh WC, Woodgett J, Boothby M, Ohashi PS. 2005. NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo. J. Immunol. 175: 3790-3799. 62. Stephenson LM, Mora AL, and Boothby M. 2005. Sequence motifs in IL-4Ra mediating cell cycle progression of primary lymphocytes. J. Immunol. 175: 5178-5185. 63. Talati M, Meyrick B, Peebles, RS Jr., Davies SS, Dworski R, Mernaugh R, Mitchell D, Boothby M, Roberts LJ, III, and Sheller JR. 2006. Oxidant stress modulates murine allergic airway responses. Free Radical Biology & Medicine 40: 1210-1219. 64. Goenka S and Boothby M. 2006. Selective potentiation of Stat-dependent gene expression by CoaSt6 (Collaborator of Stat6), a transcriptional cofactor. Proc. Natl. Acad. Sci. USA. 103: 4210-4215. 65. Zhang F and Boothby M. 2006. Switch / Sucrose Non-Fermenter complex regulation of T helper type 1 development is Stat4-dependent. J. Exp. Med. 203: 1493-1505. 66. Goenka S, Cho, S, and Boothby M. 2007. Collaborator of Stat6 (CoaSt6) functions as a poly(ADP-ribose) polymerase targeting the Stat6 cofactor p100 and mediating transcriptional function. J Biol Chem. 282: 18732-18739. 67. Adeeku, E and Boothby M. 2008. Flexibility accompanies commitment in memory CD4 lymphocytes linearly derived from IL-4 locus-activated precursors. Proc. Natl. Acad. Sci. USA. 105: 9307-9312. 68. Cho SH, Goenka S, Hentinnen T, Reikainnen A, Gudapati P, Lahesmaa R, and Boothby M. 2009. CoaSt6 (PARP-14), a member of the B Aggressive Lymphoma (BAL) gene family, transduces survival signals in primary B cells. Blood 113: 2416-2425. 69. Ford AQ, Heller NM, Stephenson L, Boothby MR, Keegan AD. 2009. An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain (V50) regulates the persistence of STAT6 phosphorylation. J Immunol 183: 1607-1616. 70. Lee K, Gudapati G, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson M, and Boothby M. 2010. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 32: 743-753. 71. Dunaway CM, Hwang Y, Lindsley CW, Cook RS, Wu JY, Boothby M, Chen J, Brantley-Sieders DM. 2011.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/21135133" Cooperative Signaling Between Slit2 and Ephrin-A1 Regulates a Balance Between Angiogenesis and Angiostasis. Mol. Cell. Biol. 31: 404-416. 72. Cho SH, Ahn A, Gudapati P, Bhargava P, Lee CH, Eischen CM, McGuinness O, and Boothby M. 2011. Glycolytic rate and lymphomagenesis depend on PARP14, an ADP-ribosyltransferase of the B Aggressive Lymphoma (BAL) family. PNAS USA 108: 15972-15977. continued 73. 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. 2011.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/22084435" IL-15 Regulates Homeostasis and Terminal Maturation of NKT Cells. J Immunol. 187: 6335-6345. 74. Lee K, Nam KT, Cho SH, Gudapati P, Hwang Y, Park DS, Potter R, Chen J, Volanakis E, Boothby M. 2012. Vital roles of mTOR complex 2 in thymocyte differentiation and Notch-driven leukemia. J. Exp. Med. 209(4): 713-28. 75. Zhuang G, Wong W, Amato K, Hwang Y, Lee K, Boothby M, Ye F, Guo Y, Shyr Y, Lin L, Carbone D, Brantley-Sieders D, Chen J. [2012] Inactivation of EphA3 tumor suppressor function by somatic mutations in lung cancer. J NCI [in press] Manuscript(s) submitted: Yang J, Katrow S, Sai J, Hawkins O, Boothby M, Ayers GD, Young E, Demicco E, Lazar A, Lev D, and Richmond A. [2012] Ikk deletion in tumor cells inhibits angiosarcoma growth while IKK deletion in myeloid cells enhances tumor growth. submitted Kim A, Stanley S, Zhou P, Robinson WS, McReynolds M, Hulbert C, Thomas JW, Alegre M. and Boothby M. NF-kB inducibility in T cells is essential for allo- and autoimmune destruction of pancreatic beta cells. Manuscript(s) in preparation: Potter RM and Boothby M. Cytokine-driven cell cycle completion after S-phase commitment requires PI 3-kinase and mTOR-mediated signal relays in primary T lymphocytes. BOOK CHAPTERS & REVIEWS: 1. Boime I, Boothby M, Hoshina M, Daniels-McQueen S, Darnell R. Expression and structure of human placental hormone genes as a function of placental development. Biol Reprod. 1982; 26, 73-91. 2. Boime I, Boothby M, Darnell R, Policastro P. Structure and expression of placental hormone genes. In: Molecular & Cellular Aspects of Reproduction. New York: Plenum Press, 1986. 3. Boothby M, Liou H-C, Finn PW, Gravallese E, Glimcher LH. Control of transcription at the murine Aa locus. Immunologic Research 1990; 9, 77-92. 4. Li S, Rothman P, Boothby M, Ferrier P, Glimcher LH, Alt F. Control of immunoglobulin heavy chain constant region gene expression. Adv. Exp. Med. Biol. 1991; 292, 245-251. 5. Boothby M, Mora AL, Aronica MA, Youn J, Sheller JR, Goenka S, and Stephenson L. IL-4 signaling, gene transcription regulation, and the control of effector T cells. Immunologic Res. 2001; 23:179-191. 6. Boothby M, Mora AL, and Stephenson L. Lymphokine-dependent proliferation of T lymphoid cells: Regulated responsiveness and role in vivo. Critical Rev. Immunol. 2001; 21:487-522. 7. Boothby M and Aronica MA. Transcription regulation, allergic responses, and asthma. Allerg. & Immunol. Clinics N. America 2002; 22:871-889. 8. Kelly-Welch AE, Hanson EM, Boothby M, and Keegan AD. Interleukin-4 and interleukin-13 signaling connections maps. Science 2003; 300:1527-1528. continued 9. Hottiger MO, Boothby M, Koch-Nolte F, Lscher B , Martin N, Plummer R, Wang Z-Q, Ziegler Mathias. 2011.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/21610250" Progress in the function and regulation of ADP-Ribosylation. Sci Signal. 4(174):mr5. doi: 10.1126/scisignal.2001645 LETTERS, COMMENTARIES, & PREVIEWS : 1. Boothby M. 2001. Specificity of sn50 for NF-kappa B?  HYPERLINK "javascript:AL_get(this, 'jour', 'Nat Immunol.');" Nat Immunol. 2(6): 471-472. 2. Boothby M. 2003. Signaling advances from immunogenetics to immunogenomics. Genome Biology 4(12): 239. 3. Boothby M. 2009.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/19464989" The calculus of integrating differentiation: timing control of T-bet. Immunity 30(5): 666-668. 4. Boothby M. 2010. Pillars of Immunology -- CRACking the Code without Rosetta: Molecular Regulation of Calcium-stimulated Gene Transcription after T cell activation. J. Immunol. 185: 4969-4971. 5. Boothby M and Lee KW. 2011.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed/21852776" A 'Tsc, Tsc' keeps the kids quie(scen)t and holds down ROS. Nat Immunol. 12(9): 811-812. [News & Views on The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function, by Yang K, Neale G, Green DR, He W, & Chi H. Nat Immmunol. (2011)] Research overview: We are studying the molecular mechanisms by which external signals regulate lymphocyte function. These signals control the survival, differentiation and proliferation of the cells which endow the immune system with specificity for foreign antigens. An overall goal in research is for the investigation of molecular pathways to lead to advances in our understanding and treatment of disease. Our proximate goals are to identify genes involved in the control of lymphocyte function, to target proteins with altered activities to defined populations of lymphocytes in intact mice by using retroviral transduction and transgenic technologies, and to evaluate the effect of these altered activities on immunity. The lymphokine interleukin 4 (IL-4) regulates critical aspects of B and T cell development such as development of T helper (Th)2 -type CD4+ lymphocytes. By studying IL-4 response elements, characterizing transcription factors that regulate these response elements, using retroviral transduction of primary T and B lymphocytes, and genetic engineering of mice, we are characterizing the cascade of signal transduction from the IL-4 receptor to the nucleus. Similarly, we are actively investigating mechanisms regulating the expression of the IFN-g gene during and after differentiation of the T helper (Th)1 subset of CD4+ T cells as well as in cytolytic CD8+ T cells. Exciting recent discoveries on these research themes include: i. Use of yeast 2-hybrid screening to identify a novel ADP-ribosyl transferase (PARP14) that collaborates with the IL-4-induced transcription factor Stat6 to regulate transcriptional activity, metabolism in B lymphocytes and macrophages, and B cell survival. Most recently, ongoing studies provide evidence that this first example of a mammalian intracellular mono-ART has an impact on susceptibility to Myc-induced lymphoma in a mouse model, a role in promoting the capacity of booster immunization to increase Ab levels, and possibly a broad role in organismal metabolic status. ii. Discovery of a new and paradigm-shifting means by which the IL-4 receptor can link to the induction of Stat6, the central transcriptional mediator of allergic processes. iii. Identification of a powerful role for the NF-kB transcription factor in regulating T cell production of the inflammatory cytokine IFN-g, preferentially impacting this aspect of responses as compared to production of the allergy-promoting cytokine IL-4, and emerging evidence on janus-like roles of NF-kB in regulation of the Th17 subset and autoimmunity. iv. Elucidation of key new steps in activation of the Ifng locus, development of a new model of how this gene is regulated in a key set of T lymphocytes, and the discovery of a novel flexibility in IFN-g gene expression regulation in memory Th2 cells. v. Elucidation of crucial roles in T cell differentiation and cell cycle regulation for rictor, an essential component of a novel mTOR-containing signal transduction complex in the PI 3-kinase pathway leading to regulation of the oncogenic pro-survival protein Akt (protein kinase B) and in turn to the NF-kB transcriptional pathway and immunological memory. IL-4 and IL-4Ra signaling play an essential role in the development of allergic processes, including atopic asthma, and NF-kB is a central actor in the inflammation elicited by microbes. Therefore, we actively use a mouse model of allergic airways disease (akin to human asthma) to investigate cellular and molecular mechanisms of disease mediated by the immune system. Using this model, we are dissecting the contributions of the IL-4 receptor and of the mTORC2 and IkB/NF-kB/Rel signaling pathways to disease. Since the adaptive evolutionary role of immunity is in defense against microbes, we also are exploring the interplay between microbial infection and the functional characteristics of memory and allergic responses using a mouse model of virus infection.     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