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John B. Harley, MD, PhD Director, Rheumatology
is a rheumatologist and biochemist with special clinical and research interests in the genetic etiology of inflammatory diseases. His experimental focus is the many genetic effects and environmental causes of systemic lupus erythematosus (SLE) and related inflammatory diseases. Through this work, nearly 50 genes are known and Epstein Barr virus has been identified to trigger the systemic autoimmunity of lupus. Dr. Harley also builds infrastructure with which to do high throughput genotyping, expression analysis, and epigenetics, which he makes available to his colleagues from around the world. In recent experiments, Dr. Harley organized the logistics of managing >18,000 subjects at >30,000 genetic markers, 3200 subjects at 1.2 million markers, and 10,000 subjects at 196,000 markers. Dr. Harley is committed to all of the steps between association detection through replication and toward identifying the possible functional genetic variants and to pursuing their biology.
Professor, UC Department of Pediatrics
Cobb BL, Fei Y, Jonsson R, Bolstad AI, Brun JG, Rischmueller M, Lester SE, Witte T, Illei G, Brennan M, Bowman S, Moser KL, Harley JB, Sawalha AH. Genetic association between methyl-CpG binding protein 2 (MECP2) and primary Sjögren’s syndrome. Ann Rheum Dis. 2010; 69(9): 1731-2.Kim-Howard X, Maiti AK, Anaya J-M, Bruner GR, Brown E, Merrill JT, Edberg JC, Petri MA, Reveille JD, Ramsey-Goldman R, Alarcon GS, Vyse TJ, Gilkeson G, Kimberly RP, James JA, Guthridge JM, Harley JB, Nath SK. ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash, and immunologic manifestations in lupus patients with European ancestry. Ann Rheum Dis. 2010.Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O'Hanlon TP, Rider LG, Jacinto FV, Lopez-Longo FJ, Dopazo J, Forn M, Peinado MA, Carreno L, Sawalha AH, Harley JB, Siebert R, Esteller M, Miller FW, Ballestar E. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res. 2010; 20(2):170-179. Harley JB, James JA. Everyone comes from somewhere: systemic lupus erythematosus and Epstein-Barr virus, induction of host interferon (INF) and humoral anti-EBNA1 immunity. Arthritis Rheum. 2010.\Bronson PG, Komorowski LK, Ramsay PP, May SL, Noble J, Lane JA, Thomson G, Claas FH, Seldin MF, Kelly JA, Harley JB, Moser KL, Gaffney PM, Behrens T, Criswell LA, Barcellos LF. Analysis of maternal-offspring HLA compatibility, parent-of-origin and noninherited effects for HLA-DRB1 in systemic lupus erythematosus. Arthritis Rheum. 2010.Heinlen LD, McClain MT, Ritterhouse LL, Bruner BF, Edgerton CC, Keith MP, James JA, Harley JB. 60kD Ro and nRNP A frequently initiate human lupus autoimmunity. PLoS ONE. 2010 5(3):e9599.
Sammalisto S, Hiekkalinna T, Schwander K, Kardia S, Weder AB, Rodriquez BL, Doria A, Kelly JA, Bruner GR, Harley JB, Redline S, Larkin EK, Patel SR, Ewan AJ, Weber JL, Perola M, Peltonen L. Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex-and population-specific genetic effects. Eur J Hum Genet. 2009 Jan 1;17(2):258-266.
Poole BD, Templeton AK, Guthridge JM, Brown EJ, Harley JB, James JA. Aberrant Epstein-Barr viral infection in systemic lupus erythematosus. Autoimmun Rev. 2009 Feb;8(4):337-42. Poole BD, Schneider RI, Guthridge JM, Velte CA, Reichlin M, Harley JB, James JA. Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus. Arthritis Rheum. 2009 Feb 26; 60(3):848-859. Han S, Kim-Howard X, Deshmukh H, Kamatani Y, Viswanathan P, Guthridge JM, Thomas K, Kaufman KM, Ojwang J, Rojas-Villarraga A, Baca V, Orozco L, Rhodes B, Choi CB, Gregersen PK, Merrill JT, James JA, Gaffney PM, Moser KL, Jacob CO, Kimberly RP, Harley JB, Bae SC, Anaya JM, Alarcon-Riquelme ME, Matsuda K, Vyse TJ, Nath SK. Evaluation of imputation-based association in and around the Integrin-α-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE). Hum Mol Genet. 2009 Mar 15;18(6):1171-80.
Molecular & Immunologic Analysis of the Pathobiology of Human Anthrax. Co-Principal Investigator. National Institute of Allergy and Infectious Diseases. Sep 2009 - Aug 2014. #AI062629-06.Genomics of Lupus. Principal Investigator. Aug 2009 - Jul 2014. #1 P01 AI083194-01.Oklahoma Autoimmunity Center of Excellence Project 2. Co-investigator. National Institute of Allergy and Infectious Diseases. May 2009 - Apr 2014. #1 U19 AI082714-01.
Genome-Wide Association Study in African-Americans with Systemic Lupus Erythematosus. Principal Investigator. Department of Defense. Sep 2010- Aug 2013. #PR094002.Genomics of Lupus Associations in the Hispanic 12q24 Linkage. Principal Investigator. National Institutes of Health. Jun 2008 - Mar 2013. #5 P01 AR049084-07.Lupus Association with Signal Transducer and Activator of Transcription 4. Principal Investigator. US Department of Veterans Affairs. Apr 2008 - Mar 2012.
Genetic Linkage in Lupus. Principal Investigator. National Institute of Allergy and Infectious Diseases. Feb 2010 - Jan 2012. #3 R37 AI024717-21S1.
Hermine I. Brunner, MD, MSc
is a pediatric rheumatologist with a special interest in clinical and translational research, focusing on pediatric lupus. Her research is focused on biomarker discovery for children with lupus and the testing of new medications for various pediatric rheumatic diseases. Dr. Brunner is also involved in trial design and provides statistical support at Cincinnati Children's and is pioneering the development of outcome measures and improving the quality of care for children with lupus and other pediatric rheumatic diseases.
Visit the Brunner Lab.
Health-related quality of life; outcome research; lupus
Economic analyses; HRQOL; measurement development; outcome research; lupus
Visit the Brunner Lab.
MD: Ludwig Maximilan University, Munich, Germany, 1991.
Residency: University of Chicago, 1997.
Fellowship: University of Toronto & Cincinnati, 1999.
MSc: Clinical Epidemiology: University of Toronto, 1999.
Certification: Pediatrics 1997; Rheumatology 2002.
Edward H. Giannini, MSc, DrPH
serves as project director for numerous clinical trials, and has vested a considerable part of his research career in the methodological aspects of conducting clinical trials in children with rheumatic diseases. In 2011 he received the
‘American College of Rheumatology Distinguished Clinical Investigator Award’
from among its 15,000 members.
Lovell DJ, Passo MH, Beukelman T, Bowyer SL, Gottlieb BS, Henrickson M, Ilowite NT, Kimura Y, DeWitt EM, Segerman J, Stein LD, Taylor J, Vehe RK, Giannini EH. Measuring process of arthritis care: a proposed set of quality measures for the process of care in juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2011 Jan;63(1):10-6. doi: 10.1002/acr.20348.
Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, Higgins G, Gottlieb B, Chon Y, Zhang N, Baumgartner SW. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010 Nov;62(11):3259-64. doi: 10.1002/art.27682.
Brunner HI, Higgins GC, Klein-Gitelman MS, Lapidus SK, Olson JC, Onel K, Punaro M, Ying J, Giannini EH. Minimal clinically important differences of disease activity indices in childhood-onset systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010 Jul;62(7):950-9.
Brunner HI, Klein-Gitelman MS, Higgins GC, Lapidus SK, Levy DM, Eberhard A, Singer N, Olson JC, Onel K, Punaro M, Schanberg L, von Scheven E, Ying J, Giannini EH. Toward the development of criteria for global flares in juvenile systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010 Jun;62(6):811-20.
Brunner HI, Higgins GC, Wiers K, Lapidus SK, Olson JC, Onel K, Punaro M, Ying J, Klein-Gitelman MS, Giannini EH. Prospective validation of the provisional criteria for the evaluation of response to therapy in childhood-onset systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010 Mar;62(3):335-44.
Giannini EH, Mehta AB, Hilz MJ, Beck M, Bichet DG, Brady RO, West M, Germain DP, Wanner C, Waldek S, Clarke JT, Mengel E, Strotmann JM, Warnock DG, Linhart A. A validated disease severity scoring system for Fabry disease. Mol Genet Metab. 2010 Mar;99(3):283-90.
Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, Higgins G, Gottlieb B, Singer NG, Chon Y, Lin SL, Baumgartner SW; Pediatric Rheumatology Collaborative Study Group. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2009 Sep;60(9):2794-804.
Carrasco R, Lovell DJ, Giannini EH, Henderson CJ, Huang B, Kramer S, Ranz J, Heubi J, Glass D. Biochemical markers of bone turnover associated with calcium supplementation in children with juvenile rheumatoid arthritis: results of a double-blind, placebo-controlled intervention trial. Arthritis Rheum. 2008 Dec;58(12):3932-40.
Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, Nemcova D, Mouy R, Sandborg C, Bohnsack J, Elewaut D, Foeldvari I, Gerloni V, Rovensky J, Minden K, Vehe RK, Weiner LW, Horneff G, Huppertz HI, Olson NY, Medich JR, Carcereri-De-Prati R, McIlraith MJ, Giannini EH, Martini A; Pediatric Rheumatology Collaborative Study Group; Pediatric Rheumatology International Trials Organisation. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008 Aug 21;359(8):810-20.
Lovell DJ, Reiff A, Ilowite NT, Wallace CA, Chon Y, Lin SL, Baumgartner SW, Giannini EH; Pediatric Rheumatology Collaborative Study Group. Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum. 2008 May;58(5):1496-504.
Alexei A. Grom, MD
Associate Professor, UC Department of Pediatrics
The research of Alexei Grom, MD, has mainly involved two translational projects focused on two autoimmune diseases – systemic juvenile rheumatoid arthritis and juvenile dermatomyositis. In both projects, recent advances of cellular immunology are applied to these diseases to promote better understanding of their pathogenesis and treatment.
Systemic Onset Juvenile Rheumatoid Arthritis and an associated condition known as Macrophage Activation Syndrome are severe and often devastating illnesses. The pathological mechanisms are not known but Dr. Alexei Grom has focused his research on NK and cytotoxic cell function in this disease. The rationale for this approach has been based on the strong clinical similarities between MAS and the better understood autosomal recessive disorder familial hemophagocytic lymphohistiocytosis, in which the uncontrolled proliferation of T cells and macrophages has been recently associated with decreased NK cell and cytotoxic cell functions secondary to mutations in the gene encoding perforin. Recent observations suggest as in FHLH, MAS patients also have profoundly depressed NK function. Moreover, a large subgroup of systemic JRA patients has very similar immunologic abnormalities. Combined with the evidence of the immunoregulatory role of NK cells in many immune responses, this suggests that NK dysfunction is relevant to the pathogenesis of MAS. New directions have thus been established for research in this poorly understood disease.
Juvenile Dermatomyositis is a chronic inflammatory condition involving primarily muscles and skin. The most characteristic feature of JDM is vascular damage associated with the capillary necrosis that eventually leads to capillary loss and tissue ischemia. The project is based on the hypothesis that capillary loss in this condition may be caused by angiostatic chemokines that are prominent in the inflammatory response in the affected muscles.
De Benedetti F, Brunner HI, Ruperto N, Kenwright, A, Ravelli A, Schneider, Woo P, Wouters C, Zemel, L, Burgos-Vargos R, Dolezalova P, Grom AA, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A. Tocilizumab in systemic juvenile idiopathic arthritis: a randomized trial. New Engl J Med. 367:2385-95. 2012.
Sikora KA, Fall N, Thornton S and Grom AA. A Markedly Low-Level of Interferon-Induced Gene Expression Distinguishes Active Systemic Juvenile Idiopathic Arthritis Synovium From other JIA subtypes: Implications for Pathogenesis of Macrophage Activation Syndrome. Arthritis Rheum. 64:3799-808. 2012.
Ruperto N, Brunner HI, Quartier P, Constantin T, Wulfraat N, Horneff G, Brik R, McCann L, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Grom AA, Magnusson, Ozen S, Abrams K, Kim D, Martini A, Lovell DJ. Canakinumab in systemic juvenile arthritis with active systemic features. New Engl J Med. 367:2396-406. 2012.
Mellins ED, Macubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nature Reviews Rheumatology. 7:416-26. 2011.
Sumegi J, Barnes MG, Lee S, Villanueva J, Zhang K, Nestheide SV, Risma K, Grom AA, AH Filipovich. Gene Expression Profiling of peripheral blood mononuclear cells from patients with untreated familial hemophagocytic lymphohistiocytosis. Blood. 117:151-60. 2011.
Barnes MG, Grom AA, Thompson SD, Griffin TA, Luyrink LK, Colbert, RA, David N, Glass DN. Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis. Arthritis Rheum. 2010.
Hinze CH, Fall N, Thornton S, Griffin TA, Thompson SD, Colbert RA, Glass DN, Michael G, Barnes BG, Grom AA. Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis. Arthritis Res Ther. 2010.
Barnes MG, Grom AA, Thompson SD, Ilowite NT, Olson JC, Sherry DD, Gottlieb BS, Aronow BJ, Pavlidis P, Hinze C, Thornton S, Griffin TA, Colbert CA, DN Glass. Gene Expression Signatures in new onset untreated juvenile idiopathic arthritis. Arthritis Rheum. 60:2102-12. 2009.
Zhang K, Biroscak J, Glass DN, Thompson S, Finkel T, Murray P, Binstadt B, Filipovich A, Grom AA. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13D polymorphisms. Arthritis Rheum. x58:2892-6. 2008.
Fall N, Barnes M, Thornton S, Luyrink L, Olson J, Ilowite NT, Gottlieb E, Griffin T, Sherry DD, Thompson S, Glass DN, Colbert RA, Grom AA. Gene expression profiling in peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum. 56:3793-804. 2007.
Michael Henrickson, MD, MPH Clinical Director
focuses on health policy development to improve national pediatric rheumatology workforce capacity. Strategies include creative policy solutions for current workforce challenges, developing telemedicine for pediatric rheumatology outreach to underserved regions, and establishing national benchmarks for clinical productivity. His second research interest is the development of global health initiatives to address the epidemiologic shift in developing countries to chronic conditions, including pediatric rheumatic diseases.
Health policy; global health; neuropsychiatric-SLE; periodic fever syndromes; systemic JIA; culturally appropriate care; quality measures
Shishov M, Henrickson M, Burgos-Vargas R, Rubio-Pérez N, Baca V, Romero-Feregrino R, Solís-Vallejo E, Huang B, Grom AA, Lovell DJ. Systemic features and early prognostic factors in Hispanic and non-Hispanic children from the United States of America and Mexico with systemic juvenile idiopathic arthritis. Clin Exp Rheumatol. 2007 Nov-Dec;25(6):907-14.
Henrickson M, Reid J, Bellet JS, Sawchuk SS, Hirsch R. Comparison of in vivo efficacy and mechanism of action of antimurine monoclonal antibodies directed against TCR alpha beta (H57-597) and CD3 (145-2C11). Transplantation. 1995 Oct 27;60(8):828-35.
Henrickson M, Giannini EH, Hirsch R. Reduction of mortality and lymphadenopathy in MRL-lpr/lpr mice treated with nonmitogenic anti-CD3 monoclonal antibody. Arthritis Rheum. 1994 Apr;37(4):587-94.
Daniel J. Lovell, MD, MPH Associate Director, Division of Rheumatology
focuses on the performance of interventional clinical trials in children with juvenile idiopathic arthritis (JIA) and other rheumatic diseases. He has served as the PI for >30 multicenter, interventional trials in JIA. Dr. Lovell is also involved in the development and validation of outcome measures and clinical response definitions for JIA, JDM and childhood onset systemic lupus erythematosus (SLE).
Associate Director, Division of Rheumatology
Diagnostic evaluation and ongoing care of children with all pediatric onset rheumatic diseases
Performance of clinical trials in children with rheumatic diseases; clinical trials methodology; mentoring of junior faculty
Lovell DJ, Passo MH, Beukelman T, Bowyer SL, Gottlieb BS, Henrickson M, Ilowite NT, Kimura Y, DeWitt EM, Segerman J, Stein LD, Taylor J, Vehe RK, Giannini EH. Measuring process of arthritis care: a proposed set of quality measures for the process of care in juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2011 Jan;63(1):10-6.
Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, Higgins G, Gottlieb B, Chon Y, Zhang N, Baumgartner SW. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010 Nov;62(11):3259-64.
Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, Higgins G, Gottlieb B, Singer NG, Chon Y, Lin SL, Baumgartner SW; Pediatric Rheumatology Collaborative Study Group. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2009 Sep;60(9):2794-804.
Seid M, Opipari L, Huang B, Brunner HI, Lovell DJ. Disease control and health-related quality of life in juvenile idiopathic arthritis. Arthritis Rheum. 2009 Mar 15;61(3):393-9.
Ting TV, Lovell DJ. Does early sulfasalazine treatment provide long-term benefits to patients with juvenile idiopathic arthritis? Nat Clin Pract Rheumatol. 2008 Jul;4(7):344-5.
Lovell DJ. Update on treatment of arthritis in children: new treatments, new goals. Bull NYU Hosp Jt Dis. 2006;64(1-2):72-6. Review.
Halima Moncrieffe, PhD
is an immunologist who has basic and translational research interests in mechanisms of childhood arthritis susceptibility and immunopathology. She studies how genetic and immunological variants contribute to inflammation and response to medication. A second research focus is investigating mechanisms of immune system suppression with specific interest in regulatory T cell function.
Instructor, UC Department of Pediatrics
Immunoregulation; juvenile idiopathic arthritis; biomarkers of response to medication
Halima Moncrieffe, PhD, is an immunologist who has basic and translational research interests in mechanisms of childhood arthritis susceptibility and immunopathology. She studies how genetic and immunological variants contribute to inflammation and response to medication. A second research focus is investigating mechanisms of immune system suppression with specific interest in regulatory T cell function.
Mulligan K, Kassoumeri L, Etheridge A, Moncrieffe H, et al. Mothers’ reports of the difficulties that their children experience in taking methotrexate for Juvenile Idiopathic Arthritis and how these impact on quality of life. Pediatr Rheumatol Online J. 2013 May 28;11(1):23.
Moncrieffe H, Ursu S, Holzinger D, Patrick F, Kassoumeri L, Wade A, Roth J, Wedderburn LR. A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein. Rheumatology (Oxford). 2013 Apr 25.
Hamaoui R, Omoyinmi E, Pesenacker, A, Nistala K, Moncrieffe H, et al. Th1 and Th17 cell subpopulations are enriched in the peripheral blood of patients with systemic juvenile idiopathic arthritis. Rheumatology. 2012 Oct;51(10):1881-6.
Holzinger D, Frosch, M, Kastrup, A, Otten, MH, Prince, FHM Suijlekom-Smit, LWA, ten Cate R, Hoppenreijs EPAH, Hansmann S, Moncrieffe H, Ursu S, Wedderburn L, Roth J, Foell D and Wittkowski H. The Toll-like receptor 4 agonist MRP8 and MRP14 protein complex is a sensitive indicator for disease activity and predicts relapses in Systemic-Onset Juvenile Idiopathic Arthritis. Ann Rheum Dis. 2012 Jun;71(6):974-80.
Hinks A, Moncrieffe H, Martin P, Ursu S, Lal S, Kassoumeri L, Weiler T, Glass DN, Thompson SD, Wedderburn LR, Thomson W. Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) gene with response to methotrexate in juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2011 Aug;70(8):1395-400.
Moncrieffe H, Hinks A, Ursu S, Kassoumeri L, Etheridge A, Hubank M, Martin P, Weiler T, Glass DN, Thompson SD, Thomson W, Wedderburn LR. Generation of novel pharmacogenomic candidates in response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype. Pharmacogenet Genomics. 2010 Nov;20(11):665-76.
Moncrieffe H, Nistala K, Kamhieh Y, Evans J, Eddaoudi A, Eaton S, Wedderburn LR. High expression of the ectonucleotidase CD39 on T cells from the inflamed site identifies two distinct populations, one regulatory and one memory T cell population. J Immunol. 2010 Jul 1;185(1):134-43.
Nistala K, Moncrieffe H, Newton KR, Hunter P, Wedderburn LR. Human IL-17 producing T cells show a reciprocal relationship to Foxp3+ regulatory T cells in childhood arthritis. Arthritis Rheum. 2008 Mar;58(3):875-87
Moncrieffe H, Coles M, Atkins C, Stockinger B. The influence of CD4 T cell subsets on control of CD4 cell mediated graft versus host disease. Immunol. 2008. Dec;125(4):459-68.
Moncrieffe H, Wedderburn LR. Regulatory T cells in Arthritis: Why Do They Fail? In Hayashi RS (Ed) Regulatory T cells. Nova Biomedical: New York 2011.
Esi Morgan DeWitt, MD, MSCE
focuses on the development and validation of patient reported outcomes measures using modern psychometric approaches, including item response theory, for improved health assessment in children. A second major research focus concerns improving clinical outcomes of patients with juvenile idiopathic arthritis through the science of quality improvement.
Childhood rheumatic diseases; juvenile idiopathic arthritis; juvenile dermatomyositis; sarcoidosis
Patient reported outcomes measure development; quality Improvement; health services research; economic evaluations; comparative effectiveness
MD: Washington University School of Medicine, St. Louis, MO, 1999.
Residency: Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, 2002.
Fellowship: Rheumatology, Children’s Hospital of Philadelphia, Philadelphia, PA, 2005.
MSCE: University of Pennsylvania, Center for Clinical Epidemiology & Biostatistics, Philadelphia, PA, 2005.
Certification: Pediatrics, 2002; Pediatric Rheumatology, 2006.
Dewitt EM, Stucky BD, Thissen D, Irwin DE, Langer M, Varni JW, Lai JS, Yeatts KB, Dewalt DA. Construction of the eight-item patient-reported outcomes measurement information system pediatric physical function scales: built using item response theory. J Clin Epidemiol. 2011 Jul;64(7):794-804.
Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, et al. American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res. 2011 Apr;63(4):465-82.
Dinan MA, Compton KL, Dhillon JK, Hammill BG, Dewitt EM, Weinfurt KP, Schulman KA. Use of patient-reported outcomes in randomized, double-blind, placebo-controlled clinical trials. Med Care. 2011 Apr;49(4):415-9.
Varni JW, Stucky BD, Thissen D, Dewitt EM, Irwin DE, Lai JS, Yeatts K, Dewalt DA. PROMIS Pediatric Pain Interference Scale: An item response theory analysis of the Pediatric Pain Item Bank. J Pain. 2010 Nov;11(11):1109-19.
Irwin DE, Stucky BD, Thissen D, Dewitt EM, Lai JS, Yeatts K, Varni JW, DeWalt DA. Sampling plan and patient characteristics of the PROMIS pediatrics large – scale survey. Qual Life Res. 2010 May;19(4):585-94.
DeWitt EM, Lin L, Glick HA, Anstrom KJ, Schulman KA, Reed SD. Pattern and predictors of the initiation of biologic agents for the treatment of rheumatoid arthritis in the United States: an analysis using a large observational data bank. Clin Ther. 2009 Aug; 31(8):1871-80; discussion 1858.
Morgan DeWitt E, Glick HA, Albert DA, Joffe M, Wolfe F. Medicare coverage of tumor necrosis factor α inhibitors as an influence on physicians’ prescribing behavior. Arch of Intern Med. 2006;166:57-63.
DeWitt EM, Schanberg LE, Rabinovich CE. Treatment of Rheumatic Diseases. In RM Kleigman, BM Stanton, J St. Geme, N Schor, RE Behrman (Eds.), Nelson Textbook of Pediatrics. 19th ed. Elsevier Saunders: Philadelphia, PA, 2011.
Wu EY, DeWitt, EM. Sarcoidosis. In RM Kleigman, BM Stanton, J St. Geme, N Schor, RE Behrman (Eds.), Nelson Textbook of Pediatrics.19th ed. Elsevier Saunders: Philadelphia, PA, 2011.
Alexey Porollo, PhD
is computational biologist with research focused on the development of new prediction methods in structural bioinformatics. He is particularly interested in prediction and analysis of protein structure, protein-protein and protein-ligand interactions. Applications of the computational approaches include structural and functional characterization of proteins and their mutations, analysis of biological pathways, identification of alternative drug targets, and virtual drug screening.
Assistant Professor, UC Department of Pediatrics
Assistant Professor, UC Department of Environmental Health
Computational biology; bioinformatics
MSc: Mari State University, Yoshkar-Ola, Russia, 1995.
PhD: Tver State University, Tver and Mari State University, Yoshkar-Ola, Russia, 1999.
Post-doc: Children’s Hospital Medical Center, Cincinnati, OH, 2006.
Syed K, Porollo A, Lam YW, Grimmett PE, Yadav JS. CYP63A2, a Catalytically Versatile Fungal P450 Monooxygenase Capable of Oxidizing Higher-Molecular-Weight Polycyclic Aromatic Hydrocarbons, Alkylphenols, and Alkanes. Appl Environ Microbiol. 2013 Apr;79(8):2692-702.
Porollo A, Meller J, Joshi Y, Jaiswal V, Smulian AG, Cushion MT. Analysis of current antifungal agents and their targets within the Pneumocystis carinii genome. Curr Drug Targets. 2012 Nov;13(12):1575-85.
Syed K, Porollo A, Lam YW, Yadav JS. A fungal P450 (CYP5136A3) capable of oxidizing polycyclic aromatic hydrocarbons and endocrine disrupting alkylphenols: role of Trp(129) and Leu(324). PLoS One. 2011;6(12):e28286.
Duran A, Amanchy R, Linares JF, Joshi J, Abu-Baker S, Porollo A, Hansen M, Moscat J, Diaz-Meco MT. p62 is a key regulator of nutrient sensing in the mTORC1 pathway. Mol Cell. 2011 Oct 7;44(1):134-46.
Porollo A, Meller J. POLYVIEW-MM: web-based platform for animation and analysis of molecular simulations. Nucleic Acids Res. 2010 Jul;38(Web Server issue):W662-6.
Porollo A, Meller J. Versatile annotation and publication quality visualization of protein complexes using POLYVIEW-3D. BMC Bioinformatics. 2007 Aug 29;8:316.
Cushion MT, Smulian AG, Slaven BE, Sesterhenn T, Arnold J, Staben C, Porollo A, Adamczak R, Meller J. Transcriptome of Pneumocystis carinii during fulminate infection: carbohydrate metabolism and the concept of a compatible parasite. PLoS One. 2007 May 9;2(5):e423.
Porollo A, Meller J. Prediction-based fingerprints of protein-protein interactions. Proteins. 2007 Feb 15;66(3):630-45.
Cao B, Porollo A, Adamczak R, Jarrell M, Meller J. Enhanced recognition of protein transmembrane domains with prediction-based structural profiles. Bioinformatics. 2006 Feb 1;22(3):303-9.
Adamczak R, Porollo A, Meller J. Accurate prediction of solvent accessibility using neural networks-based regression. Proteins. 2004 Sep 1;56(4):753-67.
Susan Thompson, PhD
Molecular basis of juvenile rheumatoid arthritis; large-scale integrative analysis of gene expression, polymorphism and other genomic data with clinical data
Visit the Thompson Lab.
Susan Thompson, PhD, has research interests that span both genetic and functional genomic studies of juvenile rheumatoid arthritis (JRA) to advance the understanding of the causes and mechanisms of disease pathogenesis. A genome-wide screen for JRA susceptibility traits has been completed and defined several regions for linkage mapping and candidate gene analysis. In addition, complementary approaches that measure global gene expression patterns using DNA microarrays are also being used to understand the molecular basis for disease.
Thompson SD, Sudman M, Ramos PS, Marion MC, Ryan M, Tsoras M, Weiler T, Wagner M, Keddache M, Haas JP, Mueller C, Prahalad S, Bohnsack J, Wise CA, Punaro M, Zhang D, Rosé CD, Comeau ME, Divers J, Glass DN, Langefeld CD. The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1. Arthritis Rheum. 2010 Nov;62(11):3265-76.
Barnes MG, Grom AA, Thompson SD, Griffin TA, Luyrink LK, Colbert RA, Glass DN. Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis. Arthritis Rheum. 2010 Nov;62(11):3249-58.
Thompson SD, Barnes MG, Griffin TA, Grom AA, Glass DN. Heterogeneity in juvenile idiopathic arthritis: impact of molecular profiling based on DNA polymorphism and gene expression patterns. Arthritis Rheum. 2010 Sep;62(9):2611-5.
Hinze CH, Fall N, Thornton S, Mo JQ, Aronow BJ, Layh-Schmitt G, Griffin TA, Thompson SD, Colbert RA, Glass DN, Barnes MG, Grom AA. Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis. Arthritis Res Ther. 2010;12(3):R123.
Barnes MG, Grom AA, Thompson SD, Griffin TA, Pavlidis P, Itert L, Fall N, Sowders DP, Hinze CH, Aronow BJ, Luyrink LK, Srivastava S, Ilowite NT, Gottlieb BS, Olson JC, Sherry DD, Glass DN, Colbert RA. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009 Jul;60(7):2102-12.
Griffin TA, Barnes MG, Ilowite NT, Olson JC, Sherry DD, Gottlieb BS, Aronow BJ, Pavlidis P, Hinze CH, Thornton S, Thompson SD, Grom AA, Colbert RA, Glass DN. Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets. Arthritis Rheum. 2009 Jul;60(7):2113-23.
Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, Binstadt BA, Filipovich A, Grom AA. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 2008 Sep;58(9):2892-6.
Chaudhari M, Moroldo MB, Shear E, Hillard P, Thompson SD, Lan D, Huang B, Brunner HI, Glass DN. Impaired reproductive fitness in mothers of children with juvenile autoimmune arthropathies. Rheumatology (Oxford). 2006 Oct;45(10):1282-7.
Phelan JD, Thompson SD. Genomic progress in pediatric arthritis: recent work and future goals. Curr Opin Rheumatol. 2006 Sep;18(5):482-9. Phelan JD, Thompson SD, Glass DN. Susceptibility to JRA/JIA: complementing general autoimmune and arthritis traits. Genes Immun. 2006 Jan;7(1):1-10.
Sherry L. Thornton, PhD
Evaluating targets for the treatment of rheumatic disease; angiogenesis; animal models of arthritis
Visit the Grom-Thornton Lab.
BS: Ball State University, Muncie, Indiana.
PhD: University of Cincinnati, College of Medicine, Cincinnati, OH.
Postdoctoral Research Fellow: Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Hinze CH, Fall N, Thornton S, Mo JQ, Aronow BJ, Layh-Schmitt G, Griffin TA, Thompson SD, Colbert RA, Glass DN, Barnes MG, Grom AA. Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis. Arthritis Res Ther. 2010;12(3):R123. Griffin TA, Barnes MG, Ilowite NT, Olson JC, Sherry DD, Gottlieb BS, Aronow BJ, Pavlidis P, Hinze CH, Thornton S, Thompson SD, Grom AA, Colbert RA, Glass DN. Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets. Arthritis Rheum. 2009 Jul;60(7):2113-23. Fall N, Barnes M, Thornton S, Luyrink L, Olson J, Ilowite NT, Gottlieb BS, Griffin T, Sherry DD, Thompson S, Glass DN, Colbert RA, Grom AA. Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum. 2007 Nov;56(11):3793-804. Flick MJ, LaJeunesse CM, Talmage KE, Witte DP, Palumbo JS, Pinkerton MD, Thornton S, Degen JL. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J Clin Invest. 2007 Nov;117(11):3224-35.
Fall N, Bove KE, Stringer K, Lovell DJ, Brunner HI, Weiss J, Higgins GC, Bowyer SL, Graham TB, Thornton S, Grom AA. Association between lack of angiogenic response in muscle tissue and high expression of angiostatic ELR-negative CXC chemokines in patients with juvenile dermatomyositis: possible link to vasculopathy. Arthritis Rheum. 2005 Oct;52(10):3175-80. Carey B, DeLay M, Strasser JE, Chalk C, Dudley-McClain K, Milligan GN, Brunner HI, Thornton S, Hirsch R. A soluble divalent class I MHC/IgG1 fusion protein activates CD8+ T cells in vivo. Clin Immunol. 2005 Jul;116(1):65-76. Huang P, Farkas T, Zhong W, Tan M, Thornton S, Morrow AL, Jiang X. Norovirus and histo-blood group antigens: demonstration of a wide spectrum of strain specificities and classification of two major binding groups among multiple binding patterns. J Virol. 2005 Jun;79(11):6714-22. Hermann LM, Pinkerton M, Jennings K, Yang L, Grom A, Sowders D, Kersten S, Witte DP, Hirsch R, Thornton S. Angiopoietin-like-4 is a potential angiogenic mediator in arthritis. Clin Immunol. 2005 Apr;115(1):93-101.
Katakura S, Jennings K, Watanabe S, Adachi E, Thornton S, Gao GP, Wilson JM, Burstein H, Trapnell B, Hirsch R. Recombinant adeno-associated virus preferentially transduces human, compared to mouse, synovium: implications for arthritis therapy. Mod Rheumatol. 2004;14(1):18-24.
Stephen N. Waggoner, PhD
is a viral immunologist whose lab studies immune regulatory mechanisms that control pathogenesis of disease. We use viruses and bacteria to probe immune functions associated with disease in mice. Our interests currently focus on a novel regulatory role of natural killer (NK) cells that influences vaccine efficacy, autoimmune disease, chronic viral infections, and immune dysfunction in the elderly.
Viral immunology; natural killer cells; immunoregulation; vaccines; autoimmunity; immune dysfunction in aging.
Visit the Waggoner Lab.
Stephen Waggoner, PhD, is an assistant professor in the Center for Autoimmune Genomics and Etiology (CAGE) within the Division of Rheumatology at Cincinnati Children's Hospital Medical Center. Dr. Waggoner received his PhD from the University of Virginia, conducted postdoctoral research at the University of Massachusetts Medical School, and joined the faculty at Cincinnati Children’s in 2013. He has garnered international recognition for his discovery that natural killer (NK) cells play a crucial regulatory role during persistent virus infection involving suppression of virus-specific T cell responses. His lab continues to explore the relevance of this phenomenon to chronic infection, vaccine efficacy, autoimmune disease, and age-associated immune dysfunction.
BA: St. Mary's College of Maryland, St. Mary's City, MD, 2000.
PhD: University of Virginia, Charlottesville, VA, 2007.
Post Doc: University of Massachusetts Medical School, Worcester, MA.
Welsh RM, Waggoner SN. NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections. Virology. 2013;435(1):37-45. Review.
Waggoner SN, Kumar V. Evolving role of 2B4/CD244 in T and NK cell responses during virus infection. Frontiers in Immunology. 2012;3:377. Review.
Waggoner SN, Cornberg M, Selin LK, Welsh RM. Natural killer cells act as rheostats modulating anti-viral T cells. Nature. 2011;481(7381):394-398.This paper is “Faculty of 1000 recommended” at: http://f1000.com/13414956
Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE, Waggoner L, Vanaja SK, Monks BG, Ganesan S, Latz E, Hornung V, Vogel SN, Szomolanyi-Tsuda E, Fitzgerald KA. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nature Immunology. 2010;11(5):395-402.
Waggoner SN, Taniguchi RT, Mathew PA, Kumar V, Welsh RM. Absence of mouse 2B4 promotes NK cell–mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. Journal of Clinical Investigation. 2010;120(6): 1925-38.
Waggoner SN, Hall CH, Hahn YS. HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. Journal of Leukocyte Biology. 2007;82(6):1407-1419.
Cruise MW, Lukens JR, Nguyen AP, Lassen MG, Waggoner SN, Hahn YS. FasL is responsible for CXCR3 chemokine induction in CD4+ T cell-dependent liver damage. Journal of Immunology. 2006;176(10):6235-6244.
Waggoner SN, Cruise MW, Kassel R, Hahn YS. gC1q receptor ligation selectively down-regulates human interleukin-12 production through activation of the phosphoinositide 3-kinase pathway. Journal of Immunology. 2005;175(7):4706-4714.
Eisen-Vandervelde A, Waggoner SN, Yao ZQ, Cale EM, Hahn CS, Hahn YS. Hepatitis C virus core selectively suppresses interleukin-12 synthesis in human macrophages by interfering with AP-1 activation. Journal of Biological Chemistry. 2004;279(42):43479-43486.
Yao ZQ, Eisen-Vandervelde A, Waggoner SN, Cale EM, Hahn YS. Direct binding of hepatitis C virus core to gC1qR on CD4+ and CD8+ T cells leads to impaired activation of Lck and Akt. Journal of Virology. 2004;78(12):6409-6419.
Matthew T. Weirauch, PhD
Transcription factors; transcriptional regulation; functional genomics; genome analysis; network-based algorithms; bioinformatics
Visit the Weirauch Lab
The staggering diversity of life on our planet stems from the elegant system encoded in our genomes. A major finding of the genomic era is that a substantial proportion of the wide range of biological form and function is likely explained by differences in gene regulation (the processes governing how and when genes are utilized), as opposed to differences in the genes themselves. An important component of gene regulation is the binding of transcription factors (TFs) to genomic DNA. A typical metazoan genome contains thousands of TFs, and knowledge of their sequence binding preferences is crucial to our understanding of the “regulatory code” governing health and disease.
Two major obstacles stand in our way before we can even begin to accurately model gene regulation. First, we must gain a thorough knowledge of the sequence binding preferences of TFs. Of an estimated 165,000 TFs present in the approximately 300 sequenced eukaryotic organisms, sequence preferences are currently known for only ~2,000 (~1%). In collaboration with Tim Hughes at the University of Toronto, I have developed a joint experimental and computational approach to determine or predict binding preferences for > 55,000 eukaryotic TFs (>30%), representing an order of magnitude improvement over our current knowledge. Second, there is an ongoing controversy surrounding the optimal way to represent TF binding preferences, and how to accurately model them to predict binding to genomic sequences. To address this issue, I have recently led the largest evaluation of computational TF binding models to date, involving 20 methods developed by researchers from around the world. Together, these two studies will provide the groundwork for the future development of models of gene regulation in both normal and disease states.
Postdoctoral Fellow: University of Toronto (Donnelly Center for Cellular and Biomolecular Research), Toronto, Ontario, Canada.
PhD: Bioinformatics, University of California Santa Cruz, Santa Cruz, California.
BSc: Computer Science, Pennsylvania State University, University Park, PA.
Weirauch M, Hughes T. A catalogue of eukaryotic transcription factor types, their evolutionary origin, and species distribution. Subcell Biochem. 2011;52:25-73. In: A Handbook of Transcription Factors, First Edition. Springer. Hughes, T, editor.
Weirauch M. Gene co-expression networks for the analysis of DNA microarray data. In: Applied Statistics for Network Biology: Methods in Systems Biology, First Edition. Wiley-VCH Verlag. Dehmer M, Emmert-Streib F, Graber A, Salvador A, editors. 2011.
Weirauch M, Hughes T. Dramatic changes in transcription factor binding over evolutionary time. Genome Biol. 2010 Jun 1;11(6):122.
Wang B, Kline C, Pastor D, Olson T, Frank B, Luu T, Sharma A, Robertson G, Weirauch M, Patierno S, Stuart J, Irby R, Lee N. Prostate apoptosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NF kappaB and microRNA network. Mol Cancer. 2010 Apr 30;9:98.
Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear E, Sevier C, Ding H, Koh J, Toufighi K, Mostafavi S, Prinz J, St Onge R, VanderSluis B, Makhnevych T, Vizeacoumar F, Alizadeh S, Bahr S, Brost R, Chen Y, Cokol M, Deshpande R, Li Z, Lin Z, Liang W, Marback M, Paw J, San Luis B, Shuteriqi E, Tong A, van Dyk N, Wallace I, Whitney J, Weirauch M, Zhong G, Zhu H, Houry W, Brudno M, Ragibizadeh S, Papp B, Pál C, Roth F, Giaever G, Nislow C, Troyanskaya O, Bussey H, Bader G, Gingras A, Morris Q, Kim P, Kaiser C, Myers C, Andrews B, Boone C. The genetic landscape of a cell. Science. 2010 Jan 22;327(5964):425-31.
Weirauch M, Hughes T. Conserved expression without conserved regulatory sequence: the more things change, the more they stay the same. Trends Genet. 2010 Feb;26(2):66-74.
Weirauch M, Wong C, Byrne A, Stuart J. Information-based methods for predicting gene function from systematic gene knock-downs. BMC Bioinformatics. 2008 Oct 29;9:463.
Byrne A, Weirauch M, Wong V, Koeva M, Dixon S, Stuart J, Roy P. A global analysis of genetic interactions in Caenorhabditis elegans. J Biol. 2007;6(3):8.
ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007 Jun 14;447(7146):799-816.
Chen C, Weirauch M, Powell C, Zambon A, Stuart J. A search engine to identify new pathway genes from expression data on multiple organisms. BMC Systems Biology. 2007 May 4;1(1):20.
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