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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  • The Role of Nanoparticle Formulation and Purification Parameters on Macrophage Drug Delivery

    Dewan, Brianna; Radvany, Martin; Truong, Nhu; Pearson, Ryan M. (2022-07-29)
  • The Advancement of Current Computational HDX-MS Analysis Methodologies Through Two Novel Packages: DCIPD and HExD-IPA

    Lowe, Vincent M.; Smith, Ally K.; Kihn, Kyle C.; Obi, Juliet; Deredge, Daniel (2022-07-29)
    EX1 and EX2 Deconvolution: Hydrogen-Deuterium exchange mass spectrometry (HDX-MS) analyzes the structural dynamics of proteins in solution through the monitoring of the time dependent exchange of the backbone amide Hydrogen with Deuterium. An exchange that is governed by the intrinsic rate of exchange (κchem) such that the closing rate (κcl) is far slower than κchem is determined to be an EX1 kinetic regime, in which all amide Hydrogens involved will be deuterated before folding. Within EX1 kinetics a bimodal isotopic distribution can arise. Bimodality within a spectra represents a mixture of EX1 and EX2 kinetics, which can be deconvoluted to obtain further insight into the system. The current program for Bimodal Deconvolution known as HxExpresss, while beneficial, lacks efficiency and ease of use. The HExD-IPA package, as presented in this poster, aims to remove those issues. Computational Integration with Experimental HDX-MS Data: In recent years, there has been a substantial interest in the integration of high-resolution computational methodologies such as MD simulations with the low resolution in vitro HDX-MS data. HDXer (HDX ensemble reweighting) is a computational software which aids in providing an objective, and quantitative, interpretation of computationally generated structural ensembles using HDX-MS data. HDXer uses a maximum entropy reweighting approach to reweight the modeled ensembles to the experimental HDX-MS data. The current methodology used to select optimal reweighting value involves the subjective determination of the inflection point from the elbow curve of Work (Bias Applied) vs Mean Standard Error (MSE) to select the optimal Work applied. The DCIPD package was developed to objectively determine the inflection point while providing a computationally more efficient methodology exploration of the Work applied.
  • Pseudomonas aeruginosa heme sensing and utilization inhibitors targeting HasAp and HemO

    Centola, Garrick; Witt, William; Hwang, Lucia; Barbier, Mariette; Wilks, Angela; Xue, Fengtian (2022-07)
  • The Regulatory Role of the Heme-Binding Protein PhuS in Pseudomonas aeruginosa

    Montes, Nicholas; Wilson, Tyree; Mouriño, Susana; Wilks, Angela (2022)
    Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that can cause life-threatening nosocomial infections in immunocompromised patients. P. aeruginosa requires iron for survival and infection and has evolved several mechanisms to sense and acquire iron from the host including the utilization of heme. PhuS is a cytoplasmic heme binding protein that regulates extracellular heme flux into P. aeruginosa through its conformational flexibility enabling it to exist in functionally distinct forms. The data presented indicates fluctuations in extracellular heme flux through PhuS can disrupt iron homeostasis through the altered expression of the prrF1/prrH sRNA network.
  • Acitretin Mimicking Inhibitors of Pseudomonas aeruginosa Heme Oxygenase (HemO)

    Aziza, Frank; Robinson, Elizabeth Ph.D.; Xue, Fengtian; Wilks, Angela (2022)
  • PATIENTS Program, Area Church Solidify Partnership

    Parks, Emily (UMB News, 2022-07-15)
    The PATIENTS Program and the Mount Lebanon Baptist Church are collaborating to build trust between academia and the West Baltimore community. Their new project, “Community Mistrust and Measures of Institutional Trustworthiness (COMMIT)" was funded by the National Institutes of Health under the Rapid Acceleration of Diagnostics for Underserved Populations initiative. This $1.2 million grant will create a sustainable model for trustworthy community-engaged research partnerships and organize a set of best practices around them.
  • Δ8-THC: An Old Cannabinoid with New Interest

    Johnson, Chad Ph.D.; Coop, Andrew; Eddington, Natalie D. (2022-07)
  • Benchmark Report on Utilization of Faculty Workload Models in Colleges and Schools of Pharmacy

    Lebovitz, Lisa; Fulford, Michael Ph.D.; Darley, Andrew PharmD, M.Ed., B.C.P.S. (2022-07)
  • Pharmapreneurial Partnerships by the University of Maryland’s Center for Innovative Pharmacy Solutions are Transforming Digital Health

    Rodriguez de Bittner, Magaly; Rochester-Eyeguokan, Charmaine D.; Osotimehin, Sadé; Sokan, Olufunke; Burns, Danielle; Lebovitz, Lisa; Eddington, Natalie D. (2022-07)
  • University of Maryland School of Pharmacy. Annual Report 2018-2019

    University of Maryland, Baltimore. School of Pharmacy, 2019
  • University of Maryland School of Pharmacy. Annual Report 2019-2020

    University of Maryland, Baltimore. School of Pharmacy, 2020
  • University of Maryland School of Pharmacy Graduate Programs

    University of Maryland, Baltimore. School of Pharmacy, 2021
  • University of Maryland School of Pharmacy Courses 2020-2022

    University of Maryland, Baltimore. School of Pharmacy (2021)
  • Doctor of Pharmacy Program and Required Curriculum

    University of Maryland, Baltimore. School of Pharmacy (2023)
  • Design, Development, and Characterization of Gallium (III) Salophen Metallotherapeutics Targeting Heme Sensing and Iron Acquisition Pathways in Pseudomonas aeruginosa

    Centola, Garrick; Wilks, Angela; Xue, Fengtian, Ph.D.; 0000-0001-5965-9545 (2022)
    The development of new antibiotics is outpaced by the rise in multi-drug resistant (MDR) bacteria, creating a global health problem. Pseudomonas aeruginosa, one such bacterium, is labeled as a “critical priority” pathogen by the WHO for its resistance to treatment and prevalence in hospital-acquired infections and immunocompromised patients where it is often life threatening. Adding to this problem, most new discoveries are derivatives of existing antibiotic classes rather than new strategies. Newer approaches targeting bacterial pathways critical to infection but not survival outside the host are expected to exert less selective pressure and slow resistance onset. One such strategy is interfering with bacterial iron uptake and utilization, as iron is a key micronutrient with several iron-regulated virulence traits used to counter iron-sequestering defense mechanisms of the host. P. aeruginosa can shift between the acquisition of labile iron stores and the more abundant heme-bound iron at various stages of infection, so inhibitors targeting these pathways must account for this adaptability. One such approach to targeting iron utilization in several forms is the use of gallium, which mimics ferric iron in ionic size and charge but cannot undergo critical redox processes, thus causing toxicity in the bacteria that acquire it under the guise of iron. This work describes the synthesis and characterization of Gallium Salophen (GaSal) and subsequent analogs targeting heme and iron acquisition pathways in P. aeruginosa. In this characterization, GaSal binds to a hemophore, HasAp, secreted by P. aeruginosa, and inhibits an extra-cytoplasmic function (ECF) signaling cascade with the outer-membrane receptor HasR, which is critical for sensing and adapting to host heme levels. GaSal is simultaneously a substrate for uptake, independent of its effect on HasAp. Using a combination of cell-based assays as well as in vitro target characterization and finally preliminary animal infection studies, GaSal and subsequent derivatives are shown to be promising new developments targeting several points in the iron uptake and utilization pathways of P. aeruginosa. Continued developments aim to retain such activity and include several routes towards further optimization and development as a therapeutic.
  • Impact of Undertreatment of Depression on Suicide and Suicide Attempt among Children and Adolescents: A Simulation Study with Microsimulation and Agent-Based Models

    Zhang, Chengchen; dosReis, Susan; 0000-0003-3349-8725 (2022)
    Background: Depression is a strong risk factor for suicide, but undertreatment of depression is common among children and adolescents. The impact of undertreatment of depression on suicidal behaviors in this population is largely unknown due to the limitations of conventional data sources and methods. This dissertation research aims to overcome these challenges by using simulation models to answer two questions: 1) Is undertreatment of depression associated with increased risk of suicidal behaviors? 2) Do interventions that reduce undertreatment of depression lower the risk of suicidal behaviors? Methods: A microsimulation model simulated the 1-year suicide rate and suicide attempt risk with 12-, 36-, 52-week antidepressant treatment and no treatment in children and adolescents with depression. Modified Poisson regression estimated the suicide rate ratios and suicide attempt risk ratios for 12-, 36- and 52-week treatment compared with no treatment. An agent-based model simulated the potential impact of the following interventions in preventing suicide and suicide attempt in a synthetic population of children and adolescents: 1) depression screening (i.e. reducing untreated depression); 2) reducing attrition during depression treatment (i.e., increasing the proportion who complete the first 12 weeks of treatment); 3) suicide intervention (i.e., screen and treat individuals who need suicide care) among depressed individuals; 4) universal suicide intervention in medical settings. Results: Compared with no treatment, 12-, 36- and 52-week antidepressant treatment was significantly associated with decreased suicide rate and risk of suicide attempt. Depression screening could reduce the risk of suicide attempt (-0.64% (95% Credible Interval (CI): -1.13%, -0.11%)) only when 80% untreated depression was reduced. Universal suicide intervention showed a significant decrease in the risk of suicide attempt, which increased with the screened proportion (20%: -0.68% (95% CI: -0.87%, -0.55%), 50%: -1.47% (95% CI: -1.61%, -1.77%), 80%: -2.89% (95% CI: -4.57%, -2.31%). The other interventions did not show a significant effect in reducing the risk of suicide attempt in the population. Conclusion: Antidepressant treatment for at least 12 weeks may reduce risk of suicidal behaviors. Universal suicide intervention in medical care settings may be more effective in reducing suicidal behaviors compared with interventions that reduce undertreatment of depression.
  • The Role of CAR and Nrf2 Dual Activation in doxorubicin/cyclophosphamide-based treatment of triple negative breast cancer

    Stern, Sydney; Wang, Hongbing, Ph.D.; 0000-0002-1479-605X (2022)
    Triple negative breast cancer (TNBC) affects 10-20% of all breast cancer cases and is associated with suboptimal outcomes due to drug resistance and/or intolerable side effects. The absence of targetable sites leaves cytotoxic chemotherapy the standard of care. Cyclophosphamide (CPA) and doxorubicin (DOX) are among the most used chemotherapeutic agents for TNBC. CPA, an alkylating prodrug, requires hepatic metabolic conversion to the rate-limiting metabolite, 4-hydroxy-cyclophosphamide (4-OH-CPA), primarily via cytochrome P450 (CYP) 2B6. Additionally, a portion of CPA is metabolized by CYP3A4 leading to a neurotoxic byproduct, chloroacetaldehyde, and an inactive byproduct, dechloroethyl-CPA. The constitutive androstane receptor (CAR, NR1I3), a nuclear receptor, regulates the expression of CYP2B6. Therefore, activation of CAR leads to preferential induction of CYP2B6 and subsequent bioactivation of CPA. On the other hand, DOX is often associated with dose-limiting cardiotoxicity. Mounting evidence suggests that this cardiotoxicity is in part attributed to the production of oxidative stress. It has been demonstrated that the activation of the nuclear factor erythroid 2-related factor (Nrf2) acts as a mediator in the protection against DOX-induced cardiotoxicity. Nrf2 regulates various antioxidant proteins and genes, such as heme-oxygenase 1 (HO-1), by binding to cis-acting antioxidant response elements in the promoter region of target genes, protecting against oxidative stress and inflammation. Our hypothesis was that dual activation of CAR and Nrf2 enhances the bioactivation of CPA while reducing DOX-mediated cardiotoxicity and improving the efficacy:toxicity ratio of CPA/DOX-based treatment for TNBC. CN06 was identified as a novel CAR and Nrf2 dual activator via high throughput screening and a chemical modification approach. Utilizing a multicellular co-culture model incorporating human primary hepatocytes, TNBC cells, and cardiomyocytes, we demonstrated that CN06 increased CPA/DOX-mediated TNBC cell death via CAR-dependent CYP2B6 induction and subsequent conversion of CPA to its active metabolite 4-hydroxy-CPA, while protecting against DOX-induced cardiotoxicity by selectively activating Nrf2-antioxidant signaling in cardiomyocytes but not in TNBC cells. Overall, these results indicate CAR and Nrf2 as a promising therapeutic strategy to improve the therapeutic index of CPA/DOX in the treatment of TNBC.

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