Person: Ahmed, Saima
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Ahmed
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Saima
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Ahmed, Saima
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Publication Biomarker Discovery for Bronchopulmonary Dysplasia Using Mass Spectrometry Based Urine Proteomics(2016-05-02) Ahmed, Saima; Steen, HannoBronchopulmonary dysplasia (BPD) is a chronic lung disorder that primarily affects premature infants. BPD commonly begins as respiratory distress syndrome (RDS) and progresses to BPD when respiratory complications persist past the original due date of the infant. BPD can last for years depending on the severity, with respiratory complications seen into adulthood for a subset of cases. To ensure the best possible health outcome, it is imperative to identify the premature infants at risk for BPD as early as possible. Given the fragility of these premature infants and the limited availability and invasive extraction of blood, I investigated the use of urine for the discovery of biomarker candidates for BPD. These samples were uniquely collected by inserting cotton balls into the diapers of these premature infants. Using less than 150 ul of urine per sample, I employed data dependent and data independent acquisition LC/MS methods to perform high throughput urine proteomics on premature infants with and without BPD. I identified several urinary proteins that show altered abundance levels in the severe BPD population. Interestingly, many of these proteins have been described before in the context of BPD, though not as urinary proteins. The identified proteins potentially point to prognostic markers to identify infants at risk of BPD and ultimately to develop novel targeted therapeutics for prevention and treatment of BPD.Publication Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures*(The American Society for Biochemistry and Molecular Biology, 2016) Oh, Djin-Ye; Dowling, David; Ahmed, Saima; Choi, Hyungwon; Brightman, Spencer; Bergelson, Ilana; Berger, Sebastian T.; Sauld, John F.; Pettengill, Matthew; Kho, Alvin; Pollack, Henry J.; Steen, Hanno; Levy, OferAdjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles, paralleling responses to adjuvant-containing vaccines in vivo. Age-specific in vitro modeling coupled with proteomics may provide fresh insight into the ontogeny of adjuvant action thereby informing targeted adjuvanted vaccine development for distinct age groups.Publication Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease(WILEY-VCH Verlag, 2013) Kentsis, Alex; Shulman, Andrew Ira; Ahmed, Saima; Brennan, Eileen; Monuteaux, Michael C; Lee, Young-Ho; Lipsett, Susan; Paulo, Joao; Dedeoglu, Fatma; Fuhlbrigge, Robert; Bachur, Richard; Bradwin, Gary; Arditi, Moshe; Sundel, Robert; Newburger, Jane; Steen, Hanno; Kim, SusanKawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high-accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case-control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.97–1 and 0.95–1, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease.