2013 Research Annual Report

Rheumatology

Division Details

Division Data Summary

Research and Training Details

Number of Faculty21
Number of Research Fellows4
Number of Research Students3
Number of Support Personnel54
Direct Annual Grant Support$5,167,310
Direct Annual Industry Support$842,437
Peer Reviewed Publications43

Clinical Activities and Training

Number of Clinical Staff3
Number of Clinical Fellows5
Inpatient Encounters307
Outpatient Encounters4865

Division Photo

Rheumatology

Row 1: H Moncrieffe, T Ting

Row 2: R Mina, E Giannini, E Morgan DeWitt, D Lovell

Row 3: M Weirauch, A Porollo, J Harley, S Thompson, M Henrickson

Row 4: M Barnes, I Chepelev, K Kaufman, S Waggoner A Grom



Significant Accomplishments

Significant Accomplishments

New Therapies for Juvenile Idiopathic Arthritis (JIA)

Phase 3 clinical trials were published by Daniel Lovell, MD, MPH, and Hermine Brunner, MD, MSc, MBA, as contributors to large collaborator studies, for treatments of the systemic form of JIA that block the cytokines IL-1 and IL-6, respectively, canakinumab and tocilizumab. These therapies are highly effective for the systemic form of JIA, which accounts for 75 percent of the deaths associated with JIA.

New Informatic Tools

Transcription factors are very important in the coordination of gene expression, making possible nearly all cellular processes. Understanding the precise sequence that they bind in DNA is important to explaining how healthy cellular processes occur (growth, division, differentiation) as well as pathological processes (cancer, anemia, inflammation). Matthew Weirauch, PhD, with colleagues in Toronto evaluated the relative merit of alternative ways of evaluating the transcription factor binding, leading to important methodologic advances for understanding these enigmatic and critically important proteins.

Micro-RNAs in Inflammation

Small RNAs called micro-RNAs appear to inhibit the expression of specific genes in cells. Nan Shen, MD and John Harley, MD, PhD have collaborated with scientists in China to explore the properties of these enigmatic molecules in inflammation. Their work shows that micro-RNA 31 contributes to the impaired production of the cytokine IL-2 in systemic lupus erythematosus. They also show that the cytokine IL-17 contributes to autoimmune pathogenesis by suppressing the expression of micro-RNA 23b, which is in turn inhibits expression of IL-17, TNFα, and IL-1β making a complex web of gene expression control.


Research Highlights

Esi Morgan DeWitt, MD

Patient Reported Outcomes Measurement Information System (PROMIS) partnering with researchers in Behavioral Medicine and Clinical Psychology, Susmita Kashikar-Zuck, PhD, and Lori Crosby, PsyD; Physical Medicine and Rehabilitation, Jilda Vargus-Adams, MD; Anesthesia (Pain Management) Kenneth Goldschneider, MD; and UC Department of Anthropology, C. Jeffrey Jacobson – have conducted validation studies of PROMIS measures in children with Juvenile Idiopathic Arthritis, chronic pain, cerebral palsy. We have developed new measures to assess pain behaviors and pain quality in children with chronic pain. Having completed the data collection portion of the study, we are in the analysis phase.

Pediatric Rheumatology Care and Outcomes Improvement Network – development of shared decision making aid to facilitate discussion and collaboration with families with JIA making treatment decisions. Partnership with Bill Brinkman, MD of the Anderson Center's Evidence and Measures team, and Ellen Lipstein, MD of Adolescent Medicine (and Anderson Center). Funded by AHRQ Center for Education and Research on Therapeutics, PI Carole Lannon.

Iouri Chepelev, PhD

Functional characterization of noncoding autoimmune disease-predisposing DNA sequence variants.

Recent genome-wide association studies have revealed that majority of disease-susceptibility loci in autoimmune diseases lie outside of the coding regions of genes and are assumed to influence transcriptional regulation rather than gene function by altering the activities of underlying regulatory elements of transcription such as enhancers and long noncoding RNAs. Our goal is to functionally characterize the role of gene-regulatory elements in the autoimmune disease etiology. Since joining the CAGE/Cincinnati Children’s faculty four months ago, my laboratory has been actively developing high-throughput experimental methods to investigate long-range chromatin interactions of enhancers and gene promoters, and a potential role of long noncoding RNAs as facilitators of these interactions.

DNA methylation, alternative pre-mRNA splicing and lupus.

The epigenome is a sensor of environmental stimuli and may thus be involved in the autoimmune disease etiology. Variants within methyl-CpG-binding protein MeCP2, a key transcription regulator which binds methylated DNA, are associated with increased susceptibility to lupus and differential gene expression in patients with SLE. CD4+ T cells isolated from active lupus patients demonstrate global DNA hypomethylation. Aberrations in alternative splicing occur in SLE, and aberrant processing of transcripts can lead to the altered function of genes involved in the immune control. Our goal is to investigate a potential mechanistic link between these two types of aberrations in SLE. As a step toward this goal, we have recently completed and published a study on the role of DNA methylation and MeCP2 in pre-mRNA splicing.

Halima Moncrieffe, PhD

Novel biomarker for identifying a subset of JIA patients who will respond to medication.

Juvenile Idiopathic Arthritis is the most common rheumatologic childhood disease. When children with arthritis fail to respond to medication this can result in disease progression, reduced quality of life and increased risk of disability. Identifying JIA patients who will respond to the standard treatment of methotrexate is an important goal. We have contributed to that goal by identifying a novel biomarker found in the serum of blood that is elevated in a subset of patients with childhood arthritis who will respond well. The article (Moncrieffe et al, Rheumatology, 2013) was featured on the MDLinx website “the world's most current index of articles that matter in the daily lives of physicians”.

P30 Pilot and Feasibility Research Funding
.

Halima Moncrieffe was awarded $60,000 for research entitled “A novel method of inducing suppressive T cells in juvenile arthritis” for two years commencing July 1st, 2013. This project was selected on a competitive basis and aims to investigate the first steps in feasibility and potential of a novel approach to therapy in childhood arthritis.

New Cincinnati Children's mentoring partnership with the ROSE program.

Halima Moncrieffe became the first mentor at Cincinnati Children's to become a partner with the ROSE (Research, Observation, Service and Education) program at the University of Cincinnati. ROSE students are “high ability, intellectually curious pre-medical college students” and integrate into the laboratory over two consecutive summers.

American Association of Immunology Award.

Dr. Moncrieffe was the recipient of an American Association of Immunology Abstract Award for an abstract entitled “Autoimmune susceptibility gene critically influences CD39 T cell expression and function in modulating human inflammation.” The award included $750 travel expenses to present these findings at the AAI 100th Annual Meeting.

Matthew Weirauch, PhD

Evaluation of methods for modeling transcription factor sequence specificity (first author paper in Nature Biotechnology)

Weirauch MT, Cote A, Norel R, Annala M, Zhao Y, Riley TR, Saez-Rodriguez J, Cokelaer T, Vedenko A, Talukder S; DREAM5 Consortium, Bussemaker HJ, Morris QD, Bulyk ML, Stolovitzky G, Hughes TR. Nat Biotechnol. 2013 Feb;31(2):126-34

Transcription factors (TFs) control gene expression by binding to short genomic sequences near the genes they control. Understanding the rules governing these binding events is crucial to understanding genome function and evolution, and also the etiology of diseases. Many approaches have been developed to model and learn a TF’s sequence binding specificity; consequently, preferences for the particular models (and methods) are very contentious. Due to the central importance of this problem to any analysis involving scanning DNA sequences for potential TF binding sites, Dr. Weirauch co-sponsored a “contest” with Tim Hughes at U. Toronto as part of the “DREAM challenge” series, which is part of the RECOMB computational biology meetings. This challenge enabled them to systematically compare a total of 26 algorithms for modeling the binding of a diverse panel of 66 TFs. The results, published in Nature Biotechnology, indicate that a simple model (the popular “Position Weight Matrix” model) performs similarly to more complex models for most of the TFs examined. The results of the evaluations not only reveal the state-of-the-art algorithms for predicting TF-DNA interactions, but also provide a resource for the further development of even better algorithms.

Michael Barnes, PhD

The Cincinnati Biobank has led the intuitional sample collection project, Better Outcomes for Children. This project obtains consent from patients as they register at the hospital to allow use of residual clinical samples for research. In the summer of 2012, we began an expansion effort to extend this project to as many areas of the hospital as possible. We are currently operating said project in 26 clinics and eight satellite campuses. Currently, about 80% of patients are consented during registration and agree to participate. We also have DNA on over 15,500 patients with more coming monthly.


Division Publications

Rheumatology Publications

  1. Adrianto I, Lin CP, Hale JJ, Levin AM, Datta I, Parker R, Adler A, Kelly JA, Kaufman KM, Lessard CJ, Moser KL, Kimberly RP, Harley JB, Iannuzzi MC, Rybicki BA, Montgomery CG. Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. PLoS One. 2012; 7:e43907.
  2. Adrianto I, Wang S, Wiley GB, Lessard CJ, Kelly JA, Adler AJ, Glenn SB, Williams AH, Ziegler JT, Comeau ME, Marion MC, Wakeland BE, Liang C, Kaufman KM, Guthridge JM, Alarcón-Riquelme ME, Biolupus, Networks G, Alarcón GS, Anaya JM, Bae SC, Kim JH, Joo YB, Boackle SA, Brown EE, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, Criswell LA, Edberg JC, Freedman BI, Gilkeson GS, Jacob CO, James JA, Kamen DL, Kimberly RP, Martin J, Merrill JT, Niewold TB, Pons-Estel BA, Scofield RH, Stevens AM, Tsao BP, Vyse TJ, Langefeld CD, Harley JB, Wakeland EK, Moser KL, Montgomery CG, Gaffney PM. Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus. Arthritis Rheum. 2012; 64:3695-705.
  3. Aggarwal R, Sestak AL, Chakravarty EF, Harley JB, Scofield RH. Excess female siblings and male fetal loss in families with systemic lupus erythematosus. J Rheumatol. 2013; 40:430-4.
  4. Barnes MG, Lynch JA, Corsmo JJ, Witte DP, Steele PE. Biobanking in Pediatric Research. In: JJ Hutton, ed. Pediatric biomedical informatics computer applications in pediatric research. New York: Springer; 2012:109-132.
  5. Biesiada J, Porollo A, Meller J. On setting up and assessing docking simulations for virtual screening. Methods Mol Biol. 2012; 928:1-16.
  6. Bruner BF, Guthridge JM, Lu R, Vidal G, Kelly JA, Robertson JM, Kamen DL, Gilkeson GS, Neas BR, Reichlin M, Scofield RH, Harley JB, James JA. Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of patients with systemic lupus erythematosus and family members. Arthritis Rheum. 2012; 64:3677-86.
  7. Chepelev I, Chen X. Alternative splicing switching in stem cell lineages. Front Biol (Beijing). 2013; 8:50-59.
  8. de Jong S, Chepelev I, Janson E, Strengman E, van den Berg LH, Veldink JH, Ophoff RA. Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner. BMC Genomics. 2012; 13:458.
  9. Deng Y, Zhao J, Sakurai D, Kaufman KM, Edberg JC, Kimberly RP, Kamen DL, Gilkeson GS, Jacob CO, Scofield RH, Langefeld CD, Kelly JA, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Alarcón GS, Vyse TJ, Pons-Estel BA, Argentine Collaborative G, Freedman BI, Gaffney PM, Sivils KM, James JA, Gregersen PK, Anaya JM, Niewold TB, Merrill JT, Criswell LA, Stevens AM, Boackle SA, Cantor RM, Chen W, Grossman JM, Hahn BH, Harley JB, Alarcόn-Riquelme ME, Biolupus, networks G, Brown EE, Tsao BP. MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus. PLoS Genet. 2013; 9:e1003336.
  10. Hu P, Chen X, Whitener RJ, Boder ET, Jones JO, Porollo A, Chen J, Zhao L. Effects of parabens on adipocyte differentiation. Toxicol Sci. 2013; 131:56-70.
  11. Kaiser R, Taylor KE, Deng Y, Zhao J, Li Y, Nititham J, Chang M, Catanese J, Begovich AB, Brown EE, Edberg JC, McGwin G, Alarcón GS, Ramsey-Goldman R, Reveille JD, Vilá LM, Petri M, Kimberly RP, Feng X, Sun L, Shen N, Li W, Lu JX, Wakeland EK, Li QZ, Yang W, Lau YL, Liu FL, Chang DM, Yu CY, Song YW, Tsao BP, Criswell LA, Hwee Siew H, the Tan Tock Seng Hospital Systemic Lupus Erythematosus Study G. Brief Report: Single-nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians. Arthritis Rheum. 2013; 65:211-5.
  12. Kaufman KM, Zhao J, Kelly JA, Hughes T, Adler A, Sánchez E, Ojwang JO, Langefeld CD, Ziegler JT, Williams AH, Comeau ME, Marion MC, Glenn SB, Cantor RM, Grossman JM, Hahn BH, Song YW, Yu CY, James JA, Guthridge JM, Brown EE, Alarcón GS, Kimberly RP, Edberg JC, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Anaya JM, Boackle SA, Stevens AM, Freedman BI, Criswell LA, Pons Estel BA, Argentine Collaborative G, Lee JH, Lee JS, Chang DM, Scofield RH, Gilkeson GS, Merrill JT, Niewold TB, Vyse TJ, Bae SC, Alarcón-Riquelme ME, network B, Jacob CO, Moser Sivils K, Gaffney PM, Harley JB, Sawalha AH, Tsao BP. Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups. Ann Rheum Dis. 2013; 72:437-44.
  13. Kim K, Brown EE, Choi CB, Alarcón-Riquelme ME, Biolupus, Kelly JA, Glenn SB, Ojwang JO, Adler A, Lee HS, Boackle SA, Criswell LA, Alarcón GS, Edberg JC, Stevens AM, Jacob CO, Gilkeson GS, Kamen DL, Tsao BP, Anaya JM, Guthridge JM, Nath SK, Richardson B, Sawalha AH, Kang YM, Shim SC, Suh CH, Lee SK, Kim CS, Merrill JT, Petri M, Ramsey-Goldman R, Vilá LM, Niewold TB, Martin J, Pons-Estel BA, GENLES, Vyse TJ, Freedman BI, Moser KL, Gaffney PM, Williams A, Comeau M, Reveille JD, James JA, Scofield RH, Langefeld CD, Kaufman KM, Harley JB, Kang C, Kimberly RP, Bae SC. Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries. Ann Rheum Dis. 2012; 71:1809-14.
  14. Leroy G, Chepelev I, Dimaggio PA, Blanco MA, Zee BM, Zhao K, Garcia BA. Proteogenomic characterization and mapping of nucleosomes decoded by Brd and HP1 proteins. Genome Biol. 2012; 13:R68.
  15. Lu R, Robertson JM, Bruner BF, Guthridge JM, Neas BR, Nath SK, Kelly JA, Moser Sivils KL, Chakravarty EF, Kamen DL, Gilkeson GS, Wallace DJ, Weisman MH, Scofield RH, Harley JB, James JA. Multiple autoantibodies display association with lymphopenia, proteinuria, and cellular casts in a large, ethnically diverse SLE patient cohort. Autoimmune Dis. 2012; 2012:819634.
  16. Luo X, Ranade K, Talker R, Jallal B, Shen N, Yao Y. microRNA-mediated regulation of innate immune response in rheumatic diseases. Arthritis Res Ther. 2013; 15:210.
  17. Ma L, Tao Y, Duran A, Llado V, Galvez A, Barger JF, Castilla EA, Chen J, Yajima T, Porollo A, Medvedovic M, Brill LM, Plas DR, Riedl SJ, Leitges M, Diaz-Meco MT, Richardson AD, Moscat J. Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis. Cell. 2013; 152:599-611.
  18. Mann IK, Chatterjee R, Zhao J, He X, Weirauch MT, Hughes TR, Vinson C. CG methylated microarrays identify a novel methylated sequence bound by the CEBPB|ATF4 heterodimer that is active in vivo. Genome Res. 2013; 23:988-97.
  19. Marsolo K, Corsmo J, Barnes MG, Pollick C, Chalfin J, Nix J, Smith C, Ganta R. Challenges in creating an opt-in biobank with a registrar-based consent process and a commercial EHR. J Am Med Inform Assoc. 2012; 19:1115-8.
  20. Molineros JE, Maiti AK, Sun C, Looger LL, Han S, Kim-Howard X, Glenn S, Adler A, Kelly JA, Niewold TB, Gilkeson GS, Brown EE, Alarcón GS, Edberg JC, Petri M, Ramsey-Goldman R, Reveille JD, Vilá LM, Freedman BI, Tsao BP, Criswell LA, Jacob CO, Moore JH, Vyse TJ, Langefeld CL, Guthridge JM, Gaffney PM, Moser KL, Scofield RH, Alarcón-Riquelme ME, Network B, Williams SM, Merrill JT, James JA, Kaufman KM, Kimberly RP, Harley JB, Nath SK. Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production. PLoS Genet. 2013; 9:e1003222.
  21. Morris DL, Taylor KE, Fernando MM, Nititham J, Alarcón-Riquelme ME, Barcellos LF, Behrens TW, Cotsapas C, Gaffney PM, Graham RR, Pons-Estel BA, Gregersen PK, Harley JB, Hauser SL, Hom G, International MHC, Autoimmunity Genetics N, Langefeld CD, Noble JA, Rioux JD, Seldin MF, Systemic Lupus Erythematosus Genetics C, Criswell LA, Vyse TJ. Unraveling multiple MHC gene associations with systemic lupus erythematosus: model choice indicates a role for HLA alleles and non-HLA genes in Europeans. Am J Hum Genet. 2012; 91:778-93.
  22. Namjou B, Keddache M, Fletcher D, Dillon S, Kottyan L, Wiley G, Gaffney PM, Wakeland BE, Liang C, Wakeland EK, Scofield RH, Kaufman K, Harley JB. Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency. Lupus. 2012; 21:1113-8.
  23. 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; 13:1575-85.
  24. Qu B, Han X, Tang Y, Shen N. A novel vector-based method for exclusive overexpression of star-form microRNAs. PLoS One. 2012; 7:e41504.
  25. Ramos PS, Oates JC, Kamen DL, Williams AH, Gaffney PM, Kelly JA, Kaufman KM, Kimberly RP, Niewold TB, Jacob CO, Tsao BP, Alarcón GS, Brown EE, Edberg JC, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, James JA, Guthridge JM, Merrill JT, Boackle SA, Freedman BI, Scofield RH, Stevens AM, Vyse TJ, Criswell LA, Moser KL, Alarcón-Riquelme ME, Langefeld CD, Harley JB, Gilkeson GS. Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry. J Rheumatol. 2013; 40:842-849.
  26. Rubicz R, Yolken R, Drigalenko E, Carless MA, Dyer TD, Bauman L, Melton PE, Kent JW, Jr., Harley JB, Curran JE, Johnson MP, Cole SA, Almasy L, Moses EK, Dhurandhar NV, Kraig E, Blangero J, Leach CT, Göring HH. A genome-wide integrative genomic study localizes genetic factors influencing antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1). PLoS Genet. 2013; 9:e1003147.
  27. Sánchez E, Rasmussen A, Riba L, Acevedo-Vasquez E, Kelly JA, Langefeld CD, Williams AH, Ziegler JT, Comeau ME, Marion MC, Garcia-De La Torre I, Maradiaga-Cecena MA, Cardiel MH, Esquivel-Valerio JA, Rodriguez-Amado J, Moctezuma JF, Miranda P, Perandones CE, Castel C, Laborde HA, Alba P, Musuruana JL, Goecke IA, Anaya JM, Kaufman KM, Adler A, Glenn SB, Brown EE, Alarcón GS, Kimberly RP, Edberg JC, Vilá LM, Criswell LA, Gilkeson GS, Niewold TB, Martin J, Vyse TJ, Boackle SA, Ramsey-Goldman R, Scofield RH, Petri M, Merrill JT, Reveille JD, Tsao BP, Orozco L, Baca V, Moser KL, Gaffney PM, James JA, Harley JB, Tusie-Luna T, Pons-Estel BA, Jacob CO, Alarcón-Riquelme ME. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations. Arthritis Rheum. 2012; 64:3687-94.
  28. Shen N, Liang D, Tang Y, de Vries N, Tak PP. MicroRNAs--novel regulators of systemic lupus erythematosus pathogenesis. Nat Rev Rheumatol. 2012; 8:701-9.
  29. Shen N, Liang D, Tang Y, Qin Y. Epigenetics of lupus. In: DJ Wallace, B Hahn, eds. Dubois' Lupus Erythematosus and Related Syndromes. Philadelphia, PA: Elsevier/Saunders; 2012:46-56.
  30. Sumegi J, Nestheide SV, Barnes MG, Villanueva J, Zhang K, Grom AA, Filipovich AH. Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis. Blood. 2013; 121:e14-24.
  31. 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; 79:2692-702.
  32. Uccellini L, De Giorgi V, Zhao Y, Tumaini B, Erdenebileg N, Dudley ME, Tomei S, Bedognetti D, Ascierto ML, Liu Q, Simon R, Kottyan L, Kaufman KM, Harley JB, Wang E, Rosenberg SA, Marincola FM. IRF5 gene polymorphisms in melanoma. J Transl Med. 2012; 10:170.
  33. Vaughn SE, Kottyan LC, Munroe ME, Harley JB. Genetic susceptibility to lupus: the biological basis of genetic risk found in B cell signaling pathways. J Leukoc Biol. 2012; 92:577-91.
  34. Waggoner SN, Kumar V. Evolving role of 2B4/CD244 in T and NK cell responses during virus infection. Front Immunol. 2012; 3:377.
  35. Wang FF, Huang XF, Shen N, Leng L, Bucala R, Chen SL, Lu LJ. A genetic role for macrophage migration inhibitory factor (MIF) in Adult-onset Still's disease. Arthritis Res Ther. 2013; 15:R65.
  36. Wang S, Adrianto I, Wiley GB, Lessard CJ, Kelly JA, Adler AJ, Glenn SB, Williams AH, Ziegler JT, Comeau ME, Marion MC, Wakeland BE, Liang C, Kaufman KM, Guthridge JM, Alarcón-Riquelme ME, Biolupus, Networks G, Alarcón GS, Anaya JM, Bae SC, Kim JH, Joo YB, Boackle SA, Brown EE, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, Criswell LA, Edberg JC, Freedman BI, Gilkeson GS, Jacob CO, James JA, Kamen DL, Kimberly RP, Martin J, Merrill JT, Niewold TB, Pons-Estel BA, Scofield RH, Stevens AM, Tsao BP, Vyse TJ, Langefeld CD, Harley JB, Wakeland EK, Moser KL, Montgomery CG, Gaffney PM. A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus. Genes Immun. 2012; 13:380-7.
  37. Weckerle CE, Mangale D, Franek BS, Kelly JA, Kumabe M, James JA, Moser KL, Harley JB, Niewold TB. Large-scale analysis of tumor necrosis factor alpha levels in systemic lupus erythematosus. Arthritis Rheum. 2012; 64:2947-52.
  38. Weirauch MT, Cote A, Norel R, Annala M, Zhao Y, Riley TR, Saez-Rodriguez J, Cokelaer T, Vedenko A, Talukder S, Dream5 Consortium, Bussemaker HJ, Morris QD, Bulyk ML, Stolovitzky G, Hughes TR. Evaluation of methods for modeling transcription factor sequence specificity. Nat Biotechnol. 2013; 31:126-34.
  39. Welsh RM, Waggoner SN. NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections. Virology. 2013; 435:37-45.
  40. Yang W, Tang H, Zhang Y, Tang X, Zhang J, Sun L, Yang J, Cui Y, Zhang L, Hirankarn N, Cheng H, Pan HF, Gao J, Lee TL, Sheng Y, Lau CS, Li Y, Chan TM, Yin X, Ying D, Lu Q, Leung AM, Zuo X, Chen X, Tong KL, Zhou F, Diao Q, Tse NK, Xie H, Mok CC, Hao F, Wong SN, Shi B, Lee KW, Hui Y, Ho MH, Liang B, Lee PP, Cui H, Guo Q, Chung BH, Pu X, Liu Q, Zhang X, Zhang C, Chong CY, Fang H, Wong RW, Sun Y, Mok MY, Li XP, Avihingsanon Y, Zhai Z, Rianthavorn P, Deekajorndej T, Suphapeetiporn K, Gao F, Shotelersuk V, Kang X, Ying SK, Zhang L, Wong WH, Zhu D, Fung SK, Zeng F, Lai WM, Wong CM, Ng IO, Garcia-Barceló MM, Cherny SS, Shen N, Tam PK, Sham PC, Ye DQ, Yang S, Zhang X, Lau YL. Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians. Am J Hum Genet. 2013; 92:41-51.
  41. Yao Y, Liu Z, Jallal B, Shen N, Rönnblom L. Type I interferons in Sjögren's syndrome. Autoimmun Rev. 2013; 12:558-66.
  42. Zhu S, Pan W, Song X, Liu Y, Shao X, Tang Y, Liang D, He D, Wang H, Liu W, Shi Y, Harley JB, Shen N, Qian Y. The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-α. Nat Med. 2012; 18:1077-86.
  43. Zhu W, Streicher K, Shen N, Higgs BW, Morehouse C, Greenlees L, Amato AA, Ranade K, Richman L, Fiorentino D, Jallal B, Greenberg SA, Yao Y. Genomic signatures characterize leukocyte infiltration in myositis muscles. BMC Med Genomics. 2012; 5:53.

Faculty, Staff, and Trainees

Faculty Members

John B. Harley, MD, PhD, Professor
Leadership Division Director
Michael Barnes, PhD, Assistant Professor
Leadership Director of Cincinnati Biobank
Hermine Brunner, MD, MSc, MBA, Professor
Iouri Chepelev, PhD, Assistant Professor
Edward H. Giannini, MSc, DrPH, Professor Emeritus
David Glass, MD, Professor Emeritus
Leadership Emeritus Associate Director of the Cincinnati Children's Research Foundation
Alexei A. Grom, MD, Associate Professor
Michael Henrickson, MD, MPH, Associate Professor
Jennifer Huggins, MD, Associate Professor
Leadership Fellowship Director
Kenneth Kaufman, PhD, Professor
Daniel Joe Lovell, MD, MPH, Professor
Leadership Joseph E. Levinson Endowed Chair in Pediatric Rheumatology; Associate Division Director; Clinic Co-Director
Rina Mina, MD, Assistant Professor
Halima Moncrieffe, PhD, Instructor
Esi Morgan DeWitt, MD, MSCE, Assistant Professor
Alexey Porollo, PhD, Assistant Professor
Nan Shen, MD, Associate Professor
Susan Thompson, PhD, Professor
Leadership Associate Division Director
Sherry Thornton, PhD, Assistant Professor
Leadership Director of the Flow Cytometry Core
Tracy Ting, MD, Assistant Professor
Leadership Clinic Co-Director
Stephen Waggoner, PhD, Assistant Professor
Matthew Weirauch, PhD, Assistant Professor

Clinical Staff Members

  • Janalee Taylor, MSN, RN, CNP

Trainees

  • Moussa El-Hallak, MD, PGY6, Memorial University Medical Center
  • Pai-Yue Lu, MD, PGY6, New York Medical College
  • Jordan Jones, MD, PGY4, Des Moines University College of Osteopathic Medicine
  • Khalid Abulaban, MD, PYG5, Gulf Medical College Amjan
  • Patricia Vega-Fernandez, MD, PGY6, University of Texas Health Science Center at San Antonio, Texas
  • Ke Liu, BS, 2003, Nanchang University
  • Samuel Vaughn, BS, 2004, Brigham Young University
  • Jiadi Xu, BS, 2010, China Agricultural University
  • Leah Kottyan, PhD, 2010, University of Cincinnati
  • Bahram Namjou, MD, 1989, Oklahoma Medical Research Foundation
  • Erin Zoller, PhD, 2011, University of Cincinnati
  • Dong Liang, PhD, 2010, Université Paris Descartes

Division Collaboration

Division of Biostatistics and Epidemiology » Bin Huang
Analyzed data from multiple clinical trials of agents for the treatment of pediatric and adult rheumatic diseases.
Division of Behavioral Medicine and Clinical Psychology »
Ongoing studies of pediatric fibromyalgia.
Division of Infectious Diseases » Margaret Hostetter
Study of a new mechanism of biofilm formation by Candida albicans. Analysis of de novo mutations as possible causative factors for osteomyelitis and recurrent staph infection.
Division of Neonatology and Pulmonary Biology » Bruce Trapnell
Analysis of possible functional implications of de novo mutations is associated with tracheal ring deformity.
Division of Hematology » Matthew Flick
Examining the effects of deficits in hemostatic factors on the pathogenesis of arthritis. We have shown that several hemostatic factors, including fibrinogen and specific regulatory domains of fibrinogen, play key roles in the pathogenesis of arthritis.
Division of Emergency Medicine » Richard Strait
Mechanism of IgG Inhibition in Inflammatory Arthritis. Our studies indicate that deficiency in IgG exacerbates arthritis in animal models. We are examining the potential mechanisms of IgG1 inhibition of inflammatory arthritis.
Division of Biomedical Informatics » Bruce Aronow and Anil Jegga
We are building an integrated computational system for data mining of huge datasets relevant to human diseases.
Division of Allergy and Immunology » Mark Rothenberg
Dr. Weirauch is involved in at least four different projects examining how transcription factor binding events contribute to the development of Eosinophilic Esophagitis.
Division of Human Genetics » C. Alexander Valencia
Dr. Weirauch has provided Bioinformatic analysis for a paper characterizing the targets of Granzyme B. Drs. Valencia and Weirauch are also applying for funding together for a joint experimental/computational platform for identifying transcription factor binding events that are disrupted by a given disease-associated genetic variant.
Division of Pediatric Urology » Joo-Seop Park
Dr. Weirauch aided in analysis of ChIP-seq results.
Division of Developmental Biology » Yutaka Yoshida
Dr. Weirauch is helping decipher the gene regulatory network controlling the expression of PLEXINA1 in the human brain.
Division of Dermatology » Kara Shah
Dr. Ting continues to have a joint Dermatology/ Rheumatology clinic with Dr. Kara Shah on a quarterly basis. This is a joint clinic to treat patients with identified or potential rheumatologic/ dermatologic conditions.
Divison of Behavioral Medicine and Clinical Psychology » Dennis Drotar
Adherence in JIA and effect on outcomes.
Division of Behavioral Medicine and Clinical Psychology » Susmita Kashikar-Zuck
Dr. Ting collaborates with Dr. Kashikar-Zuck and her lab in behavioral medicine and clinical psychology for continued research in juvenile fibromyalgia. They continue to publish the findings from the longitudinal follow-up study and are working on the development of a new combined neuromuscular training and CBT program.
Division of Human Genetics » Taosheng Huang
Collaboration with Dr. Huang to help him find a "safe place" to target a TALEN protein to the OPA1 promoter, with the goal of establishing a therapy to increase its expression levels and prevent optic atrophy.
Division of Human Genetics » Kejian Zhang and Greg Grabowski
Drs. Harley and Kaufman have been working closely with Drs. Zhang and Grabowski on the development of exome sequencing as a clinical test.
Division of Developmental Biology » Brian Gebelein
Dr. Weirauch is helping elucidate the regulatory logic of an important enhancer in Drosophila development.
Division of Allergy and Immunology » Marc Rothenberg
Drs. Harley and Kaufman are collaborating with Dr. Rotherberg on the GWAS of Eosinophilic Esophagitis.
Division of Human Genetics; Division of Endocrinology » Lisa Martin and Nancy Crimmins
Dr. Harley is collaborating on the genetics of early childhood obesity.
Division of Biomedical Informatics » John Hutton , Imre Solti , Keith Marsolo, and Michael Wagner
Dr. Harley, Cincinnati Children’s site leader for the eMERGE Network project, is working closely with Drs. Hutton, Solti, Marsolo and Wagner.
Division of Neonatology and Pulmonary Biology » Louis Muglia
Genetics of prematurity - with Drs. Harley and Kaufman
Division of Pediatric Ophthalmology » Richard Lang
Genetics of retinal toxicity of prematurity - with Drs. Harley and Kaufman.
Division of Human Genetics » Mehdi Keddache
Exome sequencing - Drs. Harley and Kaufman
Division of Human Genetics; Division of Anesthesia » Cindy Prows and Senthil Sadhasivam
Return of genetic results - Dr. Harley collaborates with Nurse Prows and Dr. Sadhasivam on various ROR projects.
Division of Clinical Pharmacology ; Division of Human Genetics » Sander Vinks , Kejian Zhang, and Cindy Prows
Dr. Harley collaborates with Drs. Vinks, Zhang and Nurse Prows on CYP2D6 data generation and incorporation with next generation pharmacogenomics data.
Division of Immunobiology » Lee Grimes
Drs. Harley and Kaufman collaborate with Dr. Grimes on exome sequencing in severe congenital neutropenia.
Division of Neonatology and Pulmonary Biology » Paul Kingma
Drs. Harley and Kaufman collaborate with Dr. Kingma on the genetics of congenital diaphragmatic hernia.
Division of Neonatology and Pulmonary Biology » Paul Kingma and James Greenberg
Drs. Harley and Kaufman collaborate with Dr. Kingma and Dr. Greenberg on various genomics projects: Polymicrogyria, Esophageal Atresia, Situs Inversus.
Division of Infectious Diseases » Peggy Hostetter
Drs. Harley and Kaufman collaborate with Dr. Hostetter on the genetics of Disseminated staph.
Division of Anesthesia » Vidya Chidambaran and Senthil Sadhasivam
Depressed Respiratory Condition with Opioid Use/Treatment - Dr. Harley
Division of Neonatology and Pulmonary Biology » Bruce Trapnell
Tracheal Ring Deformity - Dr. Harley
Division of Endocrinology » Nancy Crimmins
Early onset obesity - Dr. Harley
Division of Neonatology and Pulmonary Biology » Ardythe Morrow
genetics of neonatal necrotizing colitis - Dr. Harley
Division of Asthma Research » Neeru Hershey
Genetics of asthma - Dr. Harley
Division of Developmental & Behavioral Pediatrics » Patty Manning
Genetics of autism - Dr. Harley
Division of Bone Marrow Transplantation & Immune Deficiency ; Division of Immunobiology » Kasiani Myers and Lee Grimes
Bone marrow failure syndromes including neutropenia - Dr. Harley
Division of Experimental Hematology » Jame Mulloy
lente virus vector construction for ionizing radiation project - Dr. Harley
Division of Human Genetics ; Division of Occupational and Physical Therapy ; Division of Child Life ; Division of Behavioral Medicine and Clinical Psychology »
Dr. Ting acts as the medical leader for the Intensive Physical Therapy Program for children and adolescents with joint hypermobility and chronic pain. This recurring two week program has continued to prove successful and is quickly increasing in size. We hope to recruit additional patients for the coming year and to begin evaluating outcomes of the program.
Division of Biomedical Informatics »
Ongoing project with PR-COIN (led by Dr. Morgan DeWitt) on upload of Epic electronic health record data into the PR-COIN registry, this facilitates participation of Cincinnati Children’s in the national QI learning network to improve care and outcomes of children with JIA. This allows a data-in-once strategy, with data entered at point of care to be used for quality improvement and research.

Grants, Contracts, and Industry Agreements

Rheumatology Grants

Grant and Contract AwardsAnnual Direct

Barnes, M

Expansion of Family Aspects of a DNA Biorepository
UL1 RR 02631409/01/11-03/31/13$77,817

Brunner, H

Amgen TREAT
10/14/08-06/30/13$5,000
An Observational Registry of Abatacept in Patients with Juvenile Idiopathic Arthritis
02/01/13-01/31/23$252,616
Forecasters of Future and Progressive CKD in Patients with Microvascular Glomerular Injury
U01 DK 08567310/01/09-04/30/13$38,504
Progression of Autoimmunity During Puberty in SLE
R56 AI 08525804/01/12-08/31/13$3,660
Standardizing and Optimizing Treatment for Lupus Nephritis in Children
10/01/11-09/27/13$12,402
Childhood Arthritis and Rheumatology Research Alliance Registry ("CARRA Registry")
09/01/12-08/31/13$1,125

Grom, A

MUNC13-4 gene Polymorphisms in Macrophage Activation Syndrome and Systemic Juvenile Idiopathic Arthritis
R01 AR 05904908/08/11-07/31/16$225,000

Harley, J

Better Outcomes for Children: GWAS & PheWAS in eMERGEII
U01 HG 00682805/15/12-04/30/15$1,038,586
Genetic Linkage in Lupus
R37 AI 02471709/07/10-02/28/15$260,844
Genome-Wide Association Study in African-Americans with Systemic Lupus Erythematosus
W81XWH-10-1-067509/01/10-08/31/13$168,159
Genomics of Lupus
P01 AI 08319408/01/11-07/31/14$172,577
Identification of Diagnostic Markers for Lupus Nephritis
R21 AI 10398001/18/13-12/31/14$50,000
Genetic Lupus Associations in the Hispanic 12q24 Linkage (Project 2)
P01 AR 4908404/01/11-03/31/13$90,695

Huggins, J.

ACR REF / AMGEN Rheumatology Fellowship Training Award
07/01/13-06/30/2014$25,000

Kaufman, K

Reverse Genomics of Anti-Protective Antigen Response
U19 AI 06262909/01/11-08/31/14$30,108

Kottyan, L

Center for Environmental Genetics (Kottyan)
P30 ES 00609604/01/11-03/31/12$1,080

Lovell, D

Camp Wekandu at Camp Joy 2013
04/01/13-03/31/14$1,800
Multidisciplinary Clinical Research Center
P60 AR 04778408/18/08-07/31/13$837,145
Lovell, DanielAdministrative Core$70,673
Giannini, EdwardMethods Core$151,589
Brunner, HermineProject 1$238,624
Lovell, DanielProject 2$305,219
Grom, AlexeiProject 3$272,012
Seid, MichaelProject 4$139,417

Morgan DeWitt, E

Enhancing PROMIS in Pediatric Pain, Rheumatology, and Rehabilitation Research
U01 AR 05794009/30/09-07/31/13$415,393

Thompson, S

Gene Expression In Pediatric Arthritis
P01 AR 04892909/01/11-08/31/16$971,484
Thompson, SusanAdministrative Core$254,635
Thompson, SusanCore A$133,747
Thompson, SusanProject 3$232,213
Grom, AlexiProject 4$93,164
Harley, JohnProject 1$46,715
Lovell, DanielProject 2$38,314
Wagner, MichaelCore B$172,696

Thompson, S

Cincinnati Rheumatic Disease Core Center
P30 AR 04736308/25/11-06/30/16$395,722
Thompson, SusanAdministrative Core$267,732
Thompson, SusanCore 1$107,317
Flick, MatthewCore 2$52,222
Thornton, SherryCore 3$64,385
Wagner, MichaelCore 4$49,431
Exome Sequencing Studies in Juvenile Idiopathic Arthritis
01/01/13-12/31/14$92,593
Current Year Direct$5,167,310
Industry Contracts

Brunner, H

$35,989
$120,460
$2,986
$7,007
$3,157
$44,792

Grom, A

$10,318

Lovell, D

$8,701
$304,446
$65,895
$4,390
$153,511
$80,785
Current Year Direct Receipts$842,437
Total$6,009,747