The University of Maryland School of Pharmacy, founded in 1841, is a thriving center for life sciences research and community service. Through its education, research, and service programs, the School of Pharmacy strives to improve the health and well-being of society by aiding in the discovery, development, and use of medicines.

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  • PATIENTS Day 2019: Training for Cardiologists and their Patients about Patient-Centered Outcomes Research (PCOR)

    Cooke, Catherine E.; Burroughs, Angela; Mullins, C. Daniel; Perfetto, Eleanor M. (2019-05-31)
  • PATIENTS' Voices (2019)

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2019)
  • PATIENTS' Voices (2018)

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2018)
  • PATIENTS' Voices (2017)

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2017)
  • PATIENTS' Voices (2016)

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2016)
  • PATIENTS News (2015)

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2015)
  • PATIENTS News (2014)

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2014)
  • Correction: Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: A protocol [Syst Rev. 4, (2015) (143)] DOI: 10.1186/s13643-015-0134-z.

    Mayo-Wilson, E.; Hutfless, S.; Li, T. (BioMed Central Ltd., 2018)
    Erratum for “Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol for a systematic review” [Syst Rev. 2015] (https://www.doi.org/10.1186/s13643-015-0134-z) The correct title of the article should be "Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol". The article is a protocol for a methodological study, not a systematic review. Copyright 2018 The Author(s).
  • Effect of Cadmium Exposure on the Transport System of Organic Cation Transporters and Multidrug and Toxin Extrusion Proteins (OCTs/MATEs)

    Yang, Hong; Shu, Yan, Ph.D. (2019)
    The universal pollution by cadmium (Cd) in our agricultural land and the prevalence of cigarette smoking make the environmental Cd exposure an unneglectable human health concern. While the mechanism of cadmium accumulation has been extensively studied, no explicit mechanism has been reported regarding the elimination of cadmium from the body. On the other hand, whereas Cd exposure has been correlated with a variety of diseases, little is known pertaining to its effect on drug disposition and response in patients. Thus, we aim to delineate the mechanism of cadmium elimination and detoxification and to gain new insights into its effect on xenobiotic disposition and response. The OCTs/MATEs transport system are pair of transporter proteins highly expressed at the basolateral and apical membrane of hepatocytes and renal proximal tubules respectively. Recently, Cd has been identified as a substrate of OCTs, while we determined that MATEs could reduce the toxicity of Cd by serving as its efflux transporters in vitro. In addition, knockout of Mate1 in mice kidney resulted in higher renal toxicity in both chronic and acute Cd intoxication studies. We found that Cd was an inducer of OCT activity while an inhibitor towards MATEs in cells. Consistently, Cd exposure could lead to accumulation of the substrates of these transporters in mouse liver and kidney. Being focused on human (h) OCT2 and MATE1, our mechanistic studies revealed that hOCT2, as compared to hMATE1, was more active in trafficking between the plasma membrane and the cytoplasmic storage pool. Cd exposure could trigger the formation of a protein complex consisting of AKT2, calmodulin and AS160, which could then selectively facilitate the phosphorylation of AKT2 at T309, and initiate the translocation of hOCT2 to the plasma membrane. Altogether, our findings have identified MATE transporters as new contributors for Cd detoxification, and provided foundation to uncover environmental Cd as a previously unrecognized factor for the broad variation in drug disposition and response.
  • Water Flow-NMR—A Prospective Contact-Free In-Line Analytical Tool for Continuous Biomanufacturing

    Taraban, Marc B.; Briggs, Katharine T.; Yu, Bruce (2019)
    Continuous manufacturing of biopharmaceuticals paves way to much faster and higher quality products compared to conventional batch manufacturing. One of the most critical impediments for a wider use of continuous biomanufacturing is the lack of noninvasive analytical tools for process monitoring. We have already demonstrated that water proton transverse relaxation rate R2(1H2O) could be used to noninvasively monitor a number of important aspects of a solute state, such as protein concentration and aggregation. Here, we present the results obtained using compact low-field benchtop flow-NMR instrument capable to measure R2(1H2O) within a wide range of flow rates. Our measurements confirmed the sensitivity of R2(1H2O) to flow rate changes, protein concentration, and the content of the protein aggregates in stressed protein solutions.
  • When to include clinical study reports and regulatory documents in systematic reviews

    Jefferson, T.; Doshi, P.; Boutron, I. (BMJ Publishing Group, 2018)
    Reporting bias is a major threat to the validity and credibility of systematic reviews. This article outlines the rationale for accessing clinical study reports and other regulatory documents (regulatory data) as a means of addressing reporting bias and identifies factors that may help decide whether (or not) to include regulatory data in systematic reviews. The article also describes the origins and current state of regulatory data access and summarises a survey of current systematic reviewers' practices in considering regulatory data for inclusion in systematic reviews. How to access and extract regulatory data is not addressed. Organisations and other stakeholders such as Cochrane should encourage the use of data from clinical study reports as an important source of data in reviews of pharmaceutical interventions particularly when the intervention in question is of high importance and the risk of reporting bias is great. Copyright Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved.
  • University of Maryland School of Pharmacy Newsletter 2019

    Unknown author (University of Maryland, Baltimore. School of Pharmacy, 2019)
  • Medical Costs of Alpha-1 Antitrypsin Deficiency-associated Chronic Obstructive Pulmonary Disease in the United States

    Sieluk, Jan; Mullins, C. Daniel; 0000-0002-1833-0273
    Objectives: The objective of this study was to isolate the healthcare resource utilization and economic burden attributable to the presence of a genetic factor among Chronic Obstructive Pulmonary Disease (COPD) patients with and without Alpha-1 Antitrypsin Deficiency (AATD), twelve months before and after their initial COPD diagnosis. Methods: Retrospective analysis of OptumLabs® Data Warehouse claims (OLDW; 2000 – 2017). The OLDW is a comprehensive, longitudinal real-world data asset with de-identified lives across claims and clinical information. AATD-associated COPD cases were matched with up to 10 unique non-AATD-associated COPD controls. Healthcare resource use and costs were assigned into the following categories: office (OV), outpatient (OP), and emergency room visits (ER), inpatients stays (IP), prescription drugs (RX), and other services (OTH). A generalized linear model was used to estimate total pre- and post-index (initial COPD diagnosis) costs from a third-party payer’s perspective (2018 USD) controlling for age, gender, race/ethnicity, census region, augmentation therapy use, oxygen use, insurance type, year of COPD diagnosis, and Charlson Comorbidity Score. Healthcare resource utilization was estimated using a negative binomial regression. Results: The study population consisted of 8,881 patients (953 cases matched with 7,928 controls). The AATD-associated COPD cohort had higher expenditures and use of OV and OTH services, as well as OV, OP, ER, RX, and OTH before and after the index date, respectively. Adjusted total cost ratios for AATD-associated COPD patients as compared to controls were 2.036 [95% CI: 1.601 – 2.590] and 1.976 [95% CI: 1.550 – 2.517] while the incremental cost difference totaled $6,861 [95% CI: $3,025 - $10,698] an $5,772 [95% CI: $1,940 - $9,604] per patient before and after the index date, respectively. Conclusions: Twelve months before and after their initial COPD diagnosis, patients with AATD incur higher healthcare utilization costs that are double the cost of similar patients without AATD. This study also suggests that increased costs of AATD-associated COPD are not solely attributable to augmentation therapy use. Future studies should further explore the relationship between augmentation therapy, healthcare resource use, and other AATD-associated COPD expenditures.
  • Advances in Mass Spectrometric Structural Biology Techniques for Pattern Recognition Receptor Ligands of Microbial Origin

    Oyler, Benjamin; Goodlett, David Robinson, 1960-
    Pattern recognition receptors (PRR) are the innate immune system’s first-line sentinels for distinguishing “self” from “non-self.” Many molecules found in the bacterial cell wall are PRR ligands, including lipopolysaccharide (LPS), cardiolipin (CL), and peptidoglycan (PGN). Molecular structural biology techniques are essential for determining both basic cell biology and host-bacteria interactions through ligand-receptor binding mechanisms. Recent interest in designer PRR ligands or PRR ligand mimetics for use in drug discovery pipelines have given this research more translational value as well. Mass spectrometry (MS) has the unique capability to derive primary structures of ions as well as monitor many different ions in complex mixtures. Several different advances in PRR ligand structure analysis were achieved in this dissertation. First, chemical structure of an LPS-derived vaccine was determined using a top down tandem MS approach. Several different instrumental configurations and methods were employed to demonstrate complementarity of data and broad applicability of the approach. Second, CL from a newly discovered Actinomycete marine sponge symbiont was analyzed and compared to CL from a terrestrial Firmicute to generate hypotheses about host-bacterium interactions. This was the first molecular analysis of any secondary metabolites from this species of bacteria. Third, PGN subunits (muropeptides) from Rickettsia typhi were analyzed in a data dependent global LC-tandem MS approach. This was the first example of PGN structure discovery for R. typhi and the first example of this approach applied to PGN structure elucidation for any Rickettsiae species. All of these developments will help to advance PRR-ligand interaction research – an emerging and promising field for development of novel disease treatment and prevention approaches. Modulation of the innate immune response to bacterial insult is a challenging task without a clear understanding of underlying molecular mechanisms and how they might be manipulated by medicine. One key step in this process is development of sensitive and specific chemical analysis methods fit to acquire unequivocally interpretable data. While all of the methods described herein were applied to specific biological problems, their applicability to other scientific questions is broad.
  • Mass Spectrometry based structural analysis and systems immunoproteomics strategies deduce specifics of host-pathogen interactions

    Khan, Mohd M.; Goodlett, David Robinson, 1960-
    The innate immune system is the first line of defense against pathogens. Pattern recognition receptors (PRRs), such as the Toll-like receptors (TLRs) sense and sample pathogen-associated molecular patterns (PAMPs). On the host myeloid cell surface, the proinflammatory Gram-negative bacterial outer membrane component lipopolysaccharide (LPS, also known as endotoxin) activates the innate immune system via TLR4. Intracellularly, LPS is detected by the noncanonical inflammasome through caspase4/5/11. In the present work, mass spectrometry (MS)-based top-down structural analysis of LPS uncovered major determinants of molecular pathogenesis, and MS-based systems immunoproteomics elucidated specific features of the immune response against endotoxin. We used targeted proteomics to profile the host response to the pathogens Escherichia coli, Staphylococcus aureus, and Burkholderia cenocepacia, and we discovered significant temporal changes in the macrophage secretome. Additionally, we identified global changes in protein secretion in TLR4- and caspase11- stimulated macrophages. Finally, we observed bacterial proteomic rewiring within the biofilm forms of Burkholderia, possibly explaining the observed lowering in sensitivity to antibiotics.

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