Alfred Bothwell, PhD
Professor Emeritus of Immunobiology; Member of HTI and VBT
Research & Publications
Biography
News
Research Summary
To characterize the development and function of regulatory T cells and characterize mechanisms that affect cancer, autoimmunity, inflammation, transplantation and recruitment into vascular sites.
Extensive Research Description
The
research goals of the lab are to characterize the development and function of
regulatory T cells and characterize mechanisms that affect autoimmunity,
inflammation, transplantation and recruitment into vascular sites. Both mouse and human responses are
studied in vitro and in vivo which includes the development and use of
humanized mice. In addition, our
experience with synthetic microvessels has lead to a translational project to
revascularize islets to treat type I diabetes.
Specific accomplishments in the last year:
Specific accomplishments in the last year:
- PPARs: Peroxysome proliferated activated receptors (PPARs) represent a group of transcription factors that are critical in regulating glucose and lipid metabolism. Ligands of PPARg inhibit metabolically induced arteriosclerosis and also prevent the development of inflammatory disorders in several experimental mouse models including EAE, asthma, rheumatic arthritis and sepsis. The role of PPARg in graft arteriosclerosis (GA) has not been characterized. We therefore tested the in vivo effects of administration of the endogenously occurring ligand, 15 deoxy-prostaglandin-J2 (15-d-PGJ2), and ciglitazone and pioglitazone on vascular remodeling of human artery induced by alloreactive PBMC and the IFN-g model. The data indicate that 15-d-PGJ2 and pioglitazone significantly inhibit human GA in our in vivo human arterial graft model in immunodeficient mice. These effects appear specific because they are reversed by treatment with an antagonist, GW9662. Preliminary results suggest that it is possible to reverse disease once it is established for 3 weeks in this model.
- Microorgan Islet Grafts: The goal of this project is to bioengineer pancreatic beta cell-containing implants for treatment of diabetes. Casting the islets together with EC in collagen gels effectively revascularizes the islets in SCID/bg mice. Indeed, our pilot data indicate that these human islet-EC microorgans secrete human insulin into the peripheral blood of mice for periods of at least 4 months and demonstrate responsiveness to glucose in glucose tolerance tests. We are characterizing the structure/function properties of these microorgans in detail, including the microvessel structure and the stability of the microvessels with time. During the last year we (with Serge Kobsa and M. Saltzman) are characterizing new nanospheres that have a greater capacity to secrete factors for longer periods of time. We have shown that Hepatocyte Growth Factor (HGF) has significant anti-apoptotic activity on islets in vitro and hope to evaluate this with the new delivery systems in vivo. Inflammation and Colon Cancer: The APC/Min mouse is a highly studied model of intestinal tumorigenesis. During the last year we have shown that APC/Min mice that are deficient in the proinflammatory cytokine IL-17A have a 90% reduction in small intestinal polyps. We hope to define both the source of the IL-17A that is critical as well as the cell type that is the target of this cytokine.
Coauthors
Research Interests
Biochemistry; Biology; Biomedical Engineering; Immunogenetics
Selected Publications
- A humanized mouse model of autoimmune insulitis.Viehmann Milam AA, Maher SE, Gibson JA, Lebastchi J, Wen L, Ruddle NH, Herold KC, Bothwell AL. A humanized mouse model of autoimmune insulitis. Diabetes 2014, 63: 1712-24. PMID: 24478396, PMCID: PMC3994947, DOI: 10.2337/db13-1141.
- Interplay between DNA repair and inflammation, and the link to cancer.Kidane D, Chae WJ, Czochor J, Eckert KA, Glazer PM, Bothwell AL, Sweasy JB. Interplay between DNA repair and inflammation, and the link to cancer. Critical Reviews In Biochemistry And Molecular Biology 2014, 49: 116-39. PMID: 24410153, PMCID: PMC4300235, DOI: 10.3109/10409238.2013.875514.
- PPARγ negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation.Park HJ, Kim DH, Choi JY, Kim WJ, Kim JY, Senejani AG, Hwang SS, Kim LK, Tobiasova Z, Lee GR, Craft J, Bothwell AL, Choi JM. PPARγ negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation. PloS One 2014, 9: e99127. PMID: 24921943, PMCID: PMC4055678, DOI: 10.1371/journal.pone.0099127.
- The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation.Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-58. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.
- Mutation of POLB causes lupus in mice.Senejani AG, Liu Y, Kidane D, Maher SE, Zeiss CJ, Park HJ, Kashgarian M, McNiff JM, Zelterman D, Bothwell AL, Sweasy JB. Mutation of POLB causes lupus in mice. Cell Reports 2014, 6: 1-8. PMID: 24388753, PMCID: PMC3916967, DOI: 10.1016/j.celrep.2013.12.017.
- Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation.Park HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation. International Journal Of Molecular Sciences 2016, 17 PMID: 27548145, PMCID: PMC5000743, DOI: 10.3390/ijms17081347.
- T cell receptor-MHC class I peptide interactions: affinity, kinetics, and specificity.Corr M, Slanetz AE, Boyd LF, Jelonek MT, Khilko S, al-Ramadi BK, Kim YS, Maher SE, Bothwell AL, Margulies DH. T cell receptor-MHC class I peptide interactions: affinity, kinetics, and specificity. Science (New York, N.Y.) 1994, 265: 946-9. PMID: 8052850, DOI: 10.1126/science.8052850.
- Porcine aortic endothelial cells activate human T cells: direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28.Murray AG, Khodadoust MM, Pober JS, Bothwell AL. Porcine aortic endothelial cells activate human T cells: direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28. Immunity 1994, 1: 57-63. PMID: 7889399, DOI: 10.1016/1074-7613(94)90009-4.
- Response.Corr M, Slanetz AE, Boyd LF, Jelonek MT, Khilko S, Al-Ramadi BK, Kim YS, Maher SE, Bothwell AL, Margulies DH. Response. Science (New York, N.Y.) 1995, 268: 117. PMID: 17755235, DOI: 10.1126/science.268.5207.117.
- Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells.Maher SE, Karmann K, Min W, Hughes CC, Pober JS, Bothwell AL. Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells. Journal Of Immunology (Baltimore, Md. : 1950) 1996, 157: 3838-44. PMID: 8892613.
- Pig but not human interferon-gamma initiates human cell-mediated rejection of pig tissue in vivo.Sultan P, Murray AG, McNiff JM, Lorber MI, Askenase PW, Bothwell AL, Pober JS. Pig but not human interferon-gamma initiates human cell-mediated rejection of pig tissue in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 8767-72. PMID: 9238052, PMCID: PMC23121, DOI: 10.1073/pnas.94.16.8767.
- Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity.Kim YS, Sonn CH, Paik SG, Bothwell AL. Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity. Gene Therapy 2000, 7: 837-43. PMID: 10845721, DOI: 10.1038/sj.gt.3301175.
- Cytoprotection of human umbilical vein endothelial cells against apoptosis and CTL-mediated lysis provided by caspase-resistant Bcl-2 without alterations in growth or activation responses.Zheng L, Dengler TJ, Kluger MS, Madge LA, Schechner JS, Maher SE, Pober JS, Bothwell AL. Cytoprotection of human umbilical vein endothelial cells against apoptosis and CTL-mediated lysis provided by caspase-resistant Bcl-2 without alterations in growth or activation responses. Journal Of Immunology (Baltimore, Md. : 1950) 2000, 164: 4665-71. PMID: 10779771, DOI: 10.4049/jimmunol.164.9.4665.
- In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse.Schechner JS, Nath AK, Zheng L, Kluger MS, Hughes CC, Sierra-Honigmann MR, Lorber MI, Tellides G, Kashgarian M, Bothwell AL, Pober JS. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 9191-6. PMID: 10890921, PMCID: PMC16844, DOI: 10.1073/pnas.150242297.
- Defining the specific physiological requirements for c-Myc in T cell development.Douglas NC, Jacobs H, Bothwell AL, Hayday AC. Defining the specific physiological requirements for c-Myc in T cell development. Nature Immunology 2001, 2: 307-15. PMID: 11276201, DOI: 10.1038/86308.
- Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts.Tereb DA, Kirkiles-Smith NC, Kim RW, Wang Y, Rudic RD, Schechner JS, Lorber MI, Bothwell AL, Pober JS, Tellides G. Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts. Transplantation 2001, 71: 1622-30. PMID: 11435975, DOI: 10.1097/00007890-200106150-00023.
- Cutting Edge: Internalization of transduced E-selectin by cultured human endothelial cells: comparison of dermal microvascular and umbilical vein cells and identification of a phosphoserine-type di-leucine motif.Kluger MS, Shiao SL, Bothwell AL, Pober JS. Cutting Edge: Internalization of transduced E-selectin by cultured human endothelial cells: comparison of dermal microvascular and umbilical vein cells and identification of a phosphoserine-type di-leucine motif. Journal Of Immunology (Baltimore, Md. : 1950) 2002, 168: 2091-5. PMID: 11859093, DOI: 10.4049/jimmunol.168.5.2091.
- Interferon-gamma augments CD95(APO-1/Fas) and pro-caspase-8 expression and sensitizes human vascular endothelial cells to CD95-mediated apoptosis.Li JH, Kluger MS, Madge LA, Zheng L, Bothwell AL, Pober JS. Interferon-gamma augments CD95(APO-1/Fas) and pro-caspase-8 expression and sensitizes human vascular endothelial cells to CD95-mediated apoptosis. The American Journal Of Pathology 2002, 161: 1485-95. PMID: 12368221, PMCID: PMC1867313, DOI: 10.1016/s0002-9440(10)64424-0.
- Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction.Shim JH, Lee HK, Chang EJ, Chae WJ, Han JH, Han DJ, Morio T, Yang JJ, Bothwell A, Lee SK. Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 10617-22. PMID: 12149481, PMCID: PMC124991, DOI: 10.1073/pnas.162522099.
- Ly-6 superfamily members Ly-6A/E, Ly-6C, and Ly-6I recognize two potential ligands expressed by B lymphocytes.Pflugh DL, Maher SE, Bothwell AL. Ly-6 superfamily members Ly-6A/E, Ly-6C, and Ly-6I recognize two potential ligands expressed by B lymphocytes. Journal Of Immunology (Baltimore, Md. : 1950) 2002, 169: 5130-6. PMID: 12391229, DOI: 10.4049/jimmunol.169.9.5130.
- Porcine endothelial cells, unlike human endothelial cells, can be killed by human CTL via Fas ligand and cannot be protected by Bcl-2.Zheng L, Ben LH, Pober JS, Bothwell AL. Porcine endothelial cells, unlike human endothelial cells, can be killed by human CTL via Fas ligand and cannot be protected by Bcl-2. Journal Of Immunology (Baltimore, Md. : 1950) 2002, 169: 6850-5. PMID: 12471117, DOI: 10.4049/jimmunol.169.12.6850.
- Class II transactivator promoter activity is suppressed through regulation by a trophoblast noncoding RNA.Geirsson A, Paliwal I, Lynch RJ, Bothwell AL, Hammond GL. Class II transactivator promoter activity is suppressed through regulation by a trophoblast noncoding RNA. Transplantation 2003, 76: 387-94. PMID: 12883198, DOI: 10.1097/01.TP.0000073612.04525.46.
- Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments.Hesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG. Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments. Genes & Development 2003, 17: 37-42. PMID: 12514097, PMCID: PMC195966, DOI: 10.1101/gad.1031403.
- STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity.Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 1879-84. PMID: 12571365, PMCID: PMC149927, DOI: 10.1073/pnas.0237137100.
- Immunopathology of human T cell responses to skin, artery and endothelial cell grafts in the human peripheral blood lymphocyte/severe combined immunodeficient mouse.Pober JS, Bothwell AL, Lorber MI, McNiff JM, Schechner JS, Tellides G. Immunopathology of human T cell responses to skin, artery and endothelial cell grafts in the human peripheral blood lymphocyte/severe combined immunodeficient mouse. Springer Seminars In Immunopathology 2003, 25: 167-80. PMID: 12955465, DOI: 10.1007/s00281-003-0135-1.
- Engraftment of a vascularized human skin equivalent.Schechner JS, Crane SK, Wang F, Szeglin AM, Tellides G, Lorber MI, Bothwell AL, Pober JS. Engraftment of a vascularized human skin equivalent. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2003, 17: 2250-6. PMID: 14656987, DOI: 10.1096/fj.03-0257com.
- Receptor activator of NF-kappa B ligand stimulates recruitment of SHP-1 to the complex containing TNFR-associated factor 6 that regulates osteoclastogenesis.Zhang Z, Jimi E, Bothwell AL. Receptor activator of NF-kappa B ligand stimulates recruitment of SHP-1 to the complex containing TNFR-associated factor 6 that regulates osteoclastogenesis. Journal Of Immunology (Baltimore, Md. : 1950) 2003, 171: 3620-6. PMID: 14500659, DOI: 10.4049/jimmunol.171.7.3620.
- Human trophoblast noncoding RNA suppresses CIITA promoter III activity in murine B-lymphocytes.Geirsson A, Lynch RJ, Paliwal I, Bothwell AL, Hammond GL. Human trophoblast noncoding RNA suppresses CIITA promoter III activity in murine B-lymphocytes. Biochemical And Biophysical Research Communications 2003, 301: 718-24. PMID: 12565840, DOI: 10.1016/s0006-291x(03)00028-7.
- B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K. B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5. Nature Immunology 2004, 5: 853-61. PMID: 15258579, PMCID: PMC1635547, DOI: 10.1038/ni1099.
- Inhibition of alloresponse by a human trophoblast non-coding RNA suppressing class II transactivator promoter III and major histocompatibility class II expression in murine B-lymphocytes.Geirsson A, Bothwell AL, Hammond GL. Inhibition of alloresponse by a human trophoblast non-coding RNA suppressing class II transactivator promoter III and major histocompatibility class II expression in murine B-lymphocytes. The Journal Of Heart And Lung Transplantation : The Official Publication Of The International Society For Heart Transplantation 2004, 23: 1077-81. PMID: 15454174, DOI: 10.1016/j.healun.2004.07.020.
- Interferon alpha but not interleukin 12 activates STAT4 signaling in human vascular endothelial cells.Torpey N, Maher SE, Bothwell AL, Pober JS. Interferon alpha but not interleukin 12 activates STAT4 signaling in human vascular endothelial cells. The Journal Of Biological Chemistry 2004, 279: 26789-96. PMID: 15087447, DOI: 10.1074/jbc.M401517200.
- Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase.Fernandez-Cabezudo MJ, Vijayasarathy C, Pflugh DL, Bothwell AL, al-Ramadi BK. Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase. International Immunology 2004, 16: 1215-23. PMID: 15237112, DOI: 10.1093/intimm/dxh124.
- Bcl-2 transduction protects human endothelial cell synthetic microvessel grafts from allogeneic T cells in vivo.Zheng L, Gibson TF, Schechner JS, Pober JS, Bothwell AL. Bcl-2 transduction protects human endothelial cell synthetic microvessel grafts from allogeneic T cells in vivo. Journal Of Immunology (Baltimore, Md. : 1950) 2004, 173: 3020-6. PMID: 15322161, DOI: 10.4049/jimmunol.173.5.3020.
- Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor zeta chain ITAMs and their tyrosine residues.Chae WJ, Lee HK, Han JH, Kim SW, Bothwell AL, Morio T, Lee SK. Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor zeta chain ITAMs and their tyrosine residues. International Immunology 2004, 16: 1225-36. PMID: 15302845, DOI: 10.1093/intimm/dxh120.
- Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors.Horowitz MC, Xi Y, Pflugh DL, Hesslein DG, Schatz DG, Lorenzo JA, Bothwell AL. Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors. Journal Of Immunology (Baltimore, Md. : 1950) 2004, 173: 6583-91. PMID: 15557148, DOI: 10.4049/jimmunol.173.11.6583.
- B cells and osteoblast and osteoclast development.Horowitz MC, Bothwell AL, Hesslein DG, Pflugh DL, Schatz DG. B cells and osteoblast and osteoclast development. Immunological Reviews 2005, 208: 141-53. PMID: 16313346, DOI: 10.1111/j.0105-2896.2005.00328.x.
- Osteoporosis with increased osteoclastogenesis in hematopoietic cell-specific STAT3-deficient mice.Zhang Z, Welte T, Troiano N, Maher SE, Fu XY, Bothwell AL. Osteoporosis with increased osteoclastogenesis in hematopoietic cell-specific STAT3-deficient mice. Biochemical And Biophysical Research Communications 2005, 328: 800-7. PMID: 15694417, DOI: 10.1016/j.bbrc.2005.01.019.
- The mutant leucine-zipper domain impairs both dimerization and suppressive function of Foxp3 in T cells.Chae WJ, Henegariu O, Lee SK, Bothwell AL. The mutant leucine-zipper domain impairs both dimerization and suppressive function of Foxp3 in T cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 9631-6. PMID: 16769892, PMCID: PMC1480458, DOI: 10.1073/pnas.0600225103.
- Natural killer T cells and CD8+ T cells are dispensable for T cell-dependent allergic airway inflammation.Das J, Eynott P, Jupp R, Bothwell A, Van Kaer L, Shi Y, Das G. Natural killer T cells and CD8+ T cells are dispensable for T cell-dependent allergic airway inflammation. Nature Medicine 2006, 12: 1345-6; author reply 1347. PMID: 17151684, DOI: 10.1038/nm1206-1345.
- Pivotal roles of CD8+ T cells restricted by MHC class I-like molecules in autoimmune diseases.Das G, Das J, Eynott P, Zhang Y, Bothwell AL, Van Kaer L, Shi Y. Pivotal roles of CD8+ T cells restricted by MHC class I-like molecules in autoimmune diseases. The Journal Of Experimental Medicine 2006, 203: 2603-11. PMID: 17088432, PMCID: PMC2118151, DOI: 10.1084/jem.20060936.
- Manganese treatment modulates the expression of peroxisome proliferator-activated receptors in astrocytoma and neuroblastoma cells.Isaac AO, Kawikova I, Bothwell AL, Daniels CK, Lai JC. Manganese treatment modulates the expression of peroxisome proliferator-activated receptors in astrocytoma and neuroblastoma cells. Neurochemical Research 2006, 31: 1305-16. PMID: 17053972, DOI: 10.1007/s11064-006-9173-0.
- A limited number of genes are involved in the differentiation of germinal center B cells.Nakayama Y, Stabach P, Maher SE, Mahajan MC, Masiar P, Liao C, Zhang X, Ye ZJ, Tuck D, Bothwell AL, Newburger PE, Weissman SM. A limited number of genes are involved in the differentiation of germinal center B cells. Journal Of Cellular Biochemistry 2006, 99: 1308-25. PMID: 16795035, DOI: 10.1002/jcb.20952.
- Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study.Kawikova I, Leckman JF, Kronig H, Katsovich L, Bessen DE, Ghebremichael M, Bothwell AL. Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study. Biological Psychiatry 2007, 61: 273-8. PMID: 16996487, DOI: 10.1016/j.biopsych.2006.06.012.
- Regulatory transplantation tolerance and "stemness": evidence that Foxp3 may play a regulatory role in SOCS-3 gene transcription.Muthukumarana P, Chae WJ, Maher S, Rosengard BR, Bothwell AL, Metcalfe SM. Regulatory transplantation tolerance and "stemness": evidence that Foxp3 may play a regulatory role in SOCS-3 gene transcription. Transplantation 2007, 84: S6-11. PMID: 17632414, DOI: 10.1097/01.tp.0000269116.06510.db.
- Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis.Choi JM, Kim SH, Shin JH, Gibson T, Yoon BS, Lee DH, Lee SK, Bothwell AL, Lim JS, Lee SK. Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 19875-80. PMID: 19066215, PMCID: PMC2604944, DOI: 10.1073/pnas.0805198105.
- Interferon-gamma induces X-linked inhibitor of apoptosis-associated factor-1 and Noxa expression and potentiates human vascular smooth muscle cell apoptosis by STAT3 activation.Bai Y, Ahmad U, Wang Y, Li JH, Choy JC, Kim RW, Kirkiles-Smith N, Maher SE, Karras JG, Bennett CF, Bothwell AL, Pober JS, Tellides G. Interferon-gamma induces X-linked inhibitor of apoptosis-associated factor-1 and Noxa expression and potentiates human vascular smooth muscle cell apoptosis by STAT3 activation. The Journal Of Biological Chemistry 2008, 283: 6832-42. PMID: 18192275, DOI: 10.1074/jbc.M706021200.
- Amelioration of human allograft arterial injury by atorvastatin or simvastatin correlates with reduction of interferon-gamma production by infiltrating T cells.Yi T, Rao DA, Tang PC, Wang Y, Cuchara LA, Bothwell AL, Colangelo CM, Tellides G, Pober JS, Lorber MI. Amelioration of human allograft arterial injury by atorvastatin or simvastatin correlates with reduction of interferon-gamma production by infiltrating T cells. Transplantation 2008, 86: 719-27. PMID: 18791454, PMCID: PMC2650813, DOI: 10.1097/TP.0b013e318183eefa.
- Pax5 and linker histone H1 coordinate DNA methylation and histone modifications in the 3' regulatory region of the immunoglobulin heavy chain locus.Giambra V, Volpi S, Emelyanov AV, Pflugh D, Bothwell AL, Norio P, Fan Y, Ju Z, Skoultchi AI, Hardy RR, Frezza D, Birshtein BK. Pax5 and linker histone H1 coordinate DNA methylation and histone modifications in the 3' regulatory region of the immunoglobulin heavy chain locus. Molecular And Cellular Biology 2008, 28: 6123-33. PMID: 18644860, PMCID: PMC2547000, DOI: 10.1128/MCB.00233-08.
- Promotion of beta-cell differentiation in pancreatic precursor cells by adult islet cells.Chen W, Begum S, Opare-Addo L, Garyu J, Gibson TF, Bothwell AL, Papaioannou VE, Herold KC. Promotion of beta-cell differentiation in pancreatic precursor cells by adult islet cells. Endocrinology 2009, 150: 570-9. PMID: 18845629, PMCID: PMC2646532, DOI: 10.1210/en.2008-1009.
- Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation.Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. The Journal Of Experimental Medicine 2009, 206: 2407-16. PMID: 19808254, PMCID: PMC2768861, DOI: 10.1084/jem.20082286.
- Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice.Lepus CM, Gibson TF, Gerber SA, Kawikova I, Szczepanik M, Hossain J, Ablamunits V, Kirkiles-Smith N, Herold KC, Donis RO, Bothwell AL, Pober JS, Harding MJ. Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice. Human Immunology 2009, 70: 790-802. PMID: 19524633, PMCID: PMC2949440, DOI: 10.1016/j.humimm.2009.06.005.
- An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.Harding MJ, Lepus CM, Gibson TF, Shepherd BR, Gerber SA, Graham M, Paturzo FX, Rahner C, Madri JA, Bothwell AL, Lindenbach BD, Pober JS. An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice. PloS One 2010, 5: e9987. PMID: 20376322, PMCID: PMC2848675, DOI: 10.1371/journal.pone.0009987.
- Elevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome cases.Morer A, Chae W, Henegariu O, Bothwell AL, Leckman JF, Kawikova I. Elevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome cases. Brain, Behavior, And Immunity 2010, 24: 1069-73. PMID: 20193755, DOI: 10.1016/j.bbi.2010.02.007.
- Children with Tourette's syndrome may suffer immunoglobulin A dysgammaglobulinemia: preliminary report.Kawikova I, Grady BP, Tobiasova Z, Zhang Y, Vojdani A, Katsovich L, Richmand BJ, Park TW, Bothwell AL, Leckman JF. Children with Tourette's syndrome may suffer immunoglobulin A dysgammaglobulinemia: preliminary report. Biological Psychiatry 2010, 67: 679-83. PMID: 20006327, PMCID: PMC3974615, DOI: 10.1016/j.biopsych.2009.09.034.
- Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis.Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 5540-4. PMID: 20212110, PMCID: PMC2851824, DOI: 10.1073/pnas.0912675107.
- Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation.Choi JM, Shin JH, Sohn MH, Harding MJ, Park JH, Tobiasova Z, Kim DY, Maher SE, Chae WJ, Park SH, Lee CG, Lee SK, Bothwell AL. Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18575-80. PMID: 20937878, PMCID: PMC2972952, DOI: 10.1073/pnas.1000400107.
- Altered immunoglobulin profiles in children with Tourette syndrome.Bos-Veneman NG, Olieman R, Tobiasova Z, Hoekstra PJ, Katsovich L, Bothwell AL, Leckman JF, Kawikova I. Altered immunoglobulin profiles in children with Tourette syndrome. Brain, Behavior, And Immunity 2011, 25: 532-8. PMID: 21156204, PMCID: PMC3056238, DOI: 10.1016/j.bbi.2010.12.003.
- Peroxisome proliferator-activated receptor-γ agonists prevent in vivo remodeling of human artery induced by alloreactive T cells.Tobiasova Z, Zhang L, Yi T, Qin L, Manes TD, Kulkarni S, Lorber MI, Rodriguez FC, Choi JM, Tellides G, Pober JS, Kawikova I, Bothwell AL. Peroxisome proliferator-activated receptor-γ agonists prevent in vivo remodeling of human artery induced by alloreactive T cells. Circulation 2011, 124: 196-205. PMID: 21690493, PMCID: PMC3347886, DOI: 10.1161/CIRCULATIONAHA.110.015396.
- IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice.Chae WJ, Bothwell AL. IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice. Biochemical And Biophysical Research Communications 2011, 414: 31-6. PMID: 21939640, DOI: 10.1016/j.bbrc.2011.09.016.
- Risperidone-related improvement of irritability in children with autism is not associated with changes in serum of epidermal growth factor and interleukin-13.Tobiasova Z, van der Lingen KH, Scahill L, Leckman JF, Zhang Y, Chae W, McCracken JT, McDougle CJ, Vitiello B, Tierney E, Aman MG, Arnold LE, Katsovich L, Hoekstra PJ, Volkmar F, Bothwell AL, Kawikova I. Risperidone-related improvement of irritability in children with autism is not associated with changes in serum of epidermal growth factor and interleukin-13. Journal Of Child And Adolescent Psychopharmacology 2011, 21: 555-64. PMID: 22070180, PMCID: PMC3279715, DOI: 10.1089/cap.2010.0134.
- The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases.Choi JM, Bothwell AL. The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases. Molecules And Cells 2012, 33: 217-22. PMID: 22382683, PMCID: PMC3887706, DOI: 10.1007/s10059-012-2297-y.
- Reperfusion injury intensifies the adaptive human T cell alloresponse in a human-mouse chimeric artery model.Yi T, Fogal B, Hao Z, Tobiasova Z, Wang C, Rao DA, Al-Lamki RS, Kirkiles-Smith NC, Kulkarni S, Bradley JR, Bothwell AL, Sessa WC, Tellides G, Pober JS. Reperfusion injury intensifies the adaptive human T cell alloresponse in a human-mouse chimeric artery model. Arteriosclerosis, Thrombosis, And Vascular Biology 2012, 32: 353-60. PMID: 22053072, PMCID: PMC3262100, DOI: 10.1161/ATVBAHA.111.239285.
- Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathione.Dukhande VV, Kawikova I, Bothwell AL, Lai JC. Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathione. Apoptosis : An International Journal On Programmed Cell Death 2013, 18: 702-12. PMID: 23494481, PMCID: PMC3645366, DOI: 10.1007/s10495-013-0836-4.
- An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds.Kobsa S, Kristofik NJ, Sawyer AJ, Bothwell AL, Kyriakides TR, Saltzman WM. An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds. Biomaterials 2013, 34: 3891-901. PMID: 23453058, PMCID: PMC3625647, DOI: 10.1016/j.biomaterials.2013.02.016.
- Intranuclear interactomic inhibition of FoxP3 suppresses functions of Treg cells.Park JH, Ko JS, Shin Y, Cho JY, Oh HA, Bothwell AL, Lee SK. Intranuclear interactomic inhibition of FoxP3 suppresses functions of Treg cells. Biochemical And Biophysical Research Communications 2014, 451: 1-7. PMID: 25044110, DOI: 10.1016/j.bbrc.2014.06.141.
- The immunotherapeutic role of regulatory T cells in Leishmania (Viannia) panamensis infection.Ehrlich A, Castilho TM, Goldsmith-Pestana K, Chae WJ, Bothwell AL, Sparwasser T, McMahon-Pratt D. The immunotherapeutic role of regulatory T cells in Leishmania (Viannia) panamensis infection. Journal Of Immunology (Baltimore, Md. : 1950) 2014, 193: 2961-70. PMID: 25098291, PMCID: PMC4170189, DOI: 10.4049/jimmunol.1400728.
- Spontaneous Intestinal Tumorigenesis in Apc (/Min+) Mice Requires Altered T Cell Development with IL-17A.Chae WJ, Bothwell AL. Spontaneous Intestinal Tumorigenesis in Apc (/Min+) Mice Requires Altered T Cell Development with IL-17A. Journal Of Immunology Research 2015, 2015: 860106. PMID: 26146642, PMCID: PMC4469837, DOI: 10.1155/2015/860106.
- dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis.Lim S, Kim WJ, Kim YH, Lee S, Koo JH, Lee JA, Yoon H, Kim DH, Park HJ, Kim HM, Lee HG, Yun Kim J, Lee JU, Hun Shin J, Kyun Kim L, Doh J, Kim H, Lee SK, Bothwell AL, Suh M, Choi JM. dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis. Nature Communications 2015, 6: 8244. PMID: 26372309, PMCID: PMC4579786, DOI: 10.1038/ncomms9244.
- Snapshots of CD4+ T cell plasticity in the pathogenesis of allergic asthma.Chae WJ, Bothwell AL. Snapshots of CD4+ T cell plasticity in the pathogenesis of allergic asthma. Journal Of Thoracic Disease 2016, 8: E1010-E1012. PMID: 27747048, PMCID: PMC5059289, DOI: 10.21037/jtd.2016.08.19.
- Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen.Park HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen. Scientific Reports 2016, 6: 28495. PMID: 27335315, PMCID: PMC4917844, DOI: 10.1038/srep28495.
- Blocking MHC class II on human endothelium mitigates acute rejection.Abrahimi P, Qin L, Chang WG, Bothwell AL, Tellides G, Saltzman WM, Pober JS. Blocking MHC class II on human endothelium mitigates acute rejection. JCI Insight 2016, 1 PMID: 26900601, PMCID: PMC4756651, DOI: 10.1172/jci.insight.85293.
- Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response.Jayakumar A, Bothwell ALM. Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response. Neoplasia (New York, N.Y.) 2017, 19: 595-605. PMID: 28654863, PMCID: PMC5487300, DOI: 10.1016/j.neo.2017.04.006.
- Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis.Chae WJ, Park JH, Henegariu O, Yilmaz S, Hao L, Bothwell ALM. Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis. Immunology 2017, 152: 265-275. PMID: 28556921, PMCID: PMC5588763, DOI: 10.1111/imm.12766.
- DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation.Xiao Q, Wu J, Wang WJ, Chen S, Zheng Y, Yu X, Meeth K, Sahraei M, Bothwell ALM, Chen L, Bosenberg M, Chen J, Sexl V, Sun L, Li L, Tang W, Wu D. DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation. Nature Medicine 2018, 24: 262-270. PMID: 29431745, PMCID: PMC5840007, DOI: 10.1038/nm.4496.
- Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice.Moon JS, Mun CH, Kim JH, Cho JY, Park SD, Park TY, Shin JS, Ho CC, Park YB, Ghosh S, Bothwell ALM, Lee SW, Lee SK. Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice. Kidney International 2018, 93: 1118-1130. PMID: 29409726, DOI: 10.1016/j.kint.2017.11.017.
- Therapeutic Potential of Gene-Modified Regulatory T Cells: From Bench to Bedside.Chae WJ, Bothwell ALM. Therapeutic Potential of Gene-Modified Regulatory T Cells: From Bench to Bedside. Frontiers In Immunology 2018, 9: 303. PMID: 29503652, PMCID: PMC5820299, DOI: 10.3389/fimmu.2018.00303.
- Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection.Lim S, Kirkiles-Smith NC, Pober JS, Bothwell ALM, Choi JM. Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection. Biomaterials 2018, 183: 128-138. PMID: 30165256, PMCID: PMC6141312, DOI: 10.1016/j.biomaterials.2018.08.049.
- Canonical and Non-Canonical Wnt Signaling in Immune Cells.Chae WJ, Bothwell ALM. Canonical and Non-Canonical Wnt Signaling in Immune Cells. Trends In Immunology 2018, 39: 830-847. PMID: 30213499, PMCID: PMC7367500, DOI: 10.1016/j.it.2018.08.006.
- RIPK3-Induced Inflammation by I-MDSCs Promotes Intestinal Tumors.Jayakumar A, Bothwell ALM. RIPK3-Induced Inflammation by I-MDSCs Promotes Intestinal Tumors. Cancer Research 2019, 79: 1587-1599. PMID: 30786994, PMCID: PMC7395226, DOI: 10.1158/0008-5472.CAN-18-2153.
- Dickkopf1: An immunomodulatory ligand and Wnt antagonist in pathological inflammation.Chae WJ, Bothwell ALM. Dickkopf1: An immunomodulatory ligand and Wnt antagonist in pathological inflammation. Differentiation; Research In Biological Diversity 2019, 108: 33-39. PMID: 31221431, PMCID: PMC6982462, DOI: 10.1016/j.diff.2019.05.003.
- Functional Diversity of Myeloid-Derived Suppressor Cells: The Multitasking Hydra of Cancer.Jayakumar A, Bothwell ALM. Functional Diversity of Myeloid-Derived Suppressor Cells: The Multitasking Hydra of Cancer. Journal Of Immunology (Baltimore, Md. : 1950) 2019, 203: 1095-1103. PMID: 31427398, PMCID: PMC6703177, DOI: 10.4049/jimmunol.1900500.