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Mary Callaghan Rose, PhD
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Children's National Medical Center
Children's Research Institute (CRI)
Principal Investigator, Center for Genetic Medicine Research (CGMR)
George Washington University
School of Medicine and Health Sciences
Research Professor, Pediatrics, Biochemistry/Molecular Biology |
Contact Information
Children's National Medical Center
Center for Genetic Medicine Research (CGMR)
111 Michigan Avenue, NW
Washington, DC 20010-2970
202-476-6029
mrose2@cnmcresearch.org
Education & Training
| Institution & Location |
Degree |
Year(s) |
Field of Study |
| Emmanuel College, Boston, MA |
BA |
1965 |
Chemistry |
| John Carroll University, Cleveland, OH |
MS |
1967 |
Phys. Organic Chemistry |
| Case Western Reserve University, Cleveland, OH |
PhD |
1970 |
Chemistry |
| Duke University, Durham, NC |
Post-doc |
1970-1973 |
Chemistry |
| Duke University Medical Center, Durham, NC |
Post-doc |
1974-1976 |
Biochemistry |
Research Interests
Dr. Rose is a senior investigator in the Research Center for Genetic Medicine at Children’s National Medical Center and Associate Research Professor in the Department of Pediatrics Biochemistry, and Molecular Biology at the George Washington University School of Medicine. She earned her PhD in Chemistry at Case Western in Ohio and did her postdoctorals in Chemistry and Biochemistry at Duke University. Dr. Rose’s research interests are in asthma and cystric fibrosis-related mucus production. Overproduction of mucus contributes to airway obstruction in asthma and cystic fibrosis, thereby increasing patient morbidity and mortality. The pathways that lead to airway mucus obstruction are different in each disease and are the culmination of several complex biological processes including mucin glycoprotein hypersecretion, mucin gene regulation by inflammatory/immune response mediators, and hyperplasia of goblet cells (the major mucin-producing cells). Research projects in our laboratory focus on the areas below, which impact on the pathophysiology of mucus obstruction in airway diseases.
Regulation of airway mucin genes by inflammatory/immune response mediators.
Following exposure to pathogens or environmental toxins, inflammatory/immune response mediators are generated as part of the host immune response. Many of these mediators are now known to transcriptionally upregulate expression of mucin genes. Our studies focus on mediator-induced regulation of expression of MUC5AC, a mucin gene that encodes the protein backbone of MUC5AC mucin, a predominant component of airway secretions. Glucocorticoids are used clinically to counteract airway inflammation. We have recently shown that the glucocorticoid Dexamethasone transcriptionally cis-represses expression of the MUC5AC gene. Current studies focus on evaluating the effect of glucocorticoids on chromatin structure following upregulation of the MUC5AC gene by inflammatory mediators. Some inflammatory mediators, such as IL8, increase the abundance of MUC5AC mRNA and do so by increasing transcript stability. Increased mRNA stability is typically regulated by sequences in the 3’ untranslated regions (UTR) of genes. Some IL8-responsive domains in the MUC5AC 3’ UTR have now been identified by RNA-EMSA using biotinylated RNA oligonucleotide probes. The identity of RNA-binding proteins is being established and functional studies are underway.
Genes and mechanisms that induce goblet cell metaplasia in murine airways.
We are using the IL13-induced murine model of allergic asthma to identify pathways that lead to the induction of goblet cells in the airway epithelium of mice with allergic asthma. This pathway is known to be mediated by the IL4Rx and the transcription factor Stat6. Ongoing studies have identified several candidate master and switch genes by expression array analyses of IL13-exposed or control murine trachea. Current studies focus on validating master genes with Stat6 cis-responsive elements that regulate downstream targets that lead to goblet cell metaplasia. Subsequent studies will focus on identification and functional assessment of switch genes that induce airway goblet cell differentiation.
The role of mucins in innate immunity.
The functional role of mucins in mucosal immunology is not at all well understood. We have recently shown that MUC7 mucin is present in the airway secretions of asthmatic, but not non-asthmatic, pediatric patients and that MUC7 mucin/peptides are induced in the airway secretions of infants following RSV infection. The question of whether MUC7 mucin levels are induced in the airways of infants with chronic lung disease is being investigated to determine whether MUC7 mucin is an innate immune responder to lung viral infection or to chronic inflammation. The mechanisms whereby MUC7 is expressed and mediated in the airways in response to viral infection and cytokines induced by viral infections are being investigated.
Publications
View a partial list of Mary Callaghan Rose's publications through the National Library of Medicine's PubMed online database.
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