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.