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Item Dysferlin’s C2a Domain, Ca2+ Binding and Pkcα Suppress Ryr1-mediated Ca2+ Leak Into the Triad Junction(2025-02-15) Bloch, Robert J.; Lukyanenko, Valeriy; Muriel, Joaquin M.; Garman, DanielDysferlin is an integral membrane protein of the triad junction (TJ). It absence in skeletal muscle leads to Limb Girdle Muscular Dystrophy R2, an autosomal recessive disease. Our studies of dysferlin-null mouse myofibers in vitro show the following. (i) Mild injury by hypoosmotic shock decreases the amplitude of the voltage-induced Ca2+ transient and generates Ca2+ waves via Ca2+-induced Ca2+ release (CICR). (ii) These effects are suppressed by drugs that stabilize the DHPR-RyR1 couplon or inhibit RyR1 Ca2+ leak. (iii) They are also suppressed by low concentrations (10nM) of BAPTA-AM in the bathing medium; (iv) BAPTAAM also increases the voltage-induced Ca2+ transient amplitude in dysferlin-null fibers, bringing them to control levels. (v) Dysferlin’s C2A domain binds Ca2+. A chimera in which C2A is replaced with GCaMP6fu, which binds Ca2+ rapidly, targets TJs normally and suppresses abnormal Ca2+ signaling. (vi) Expression of dysferlin’s C2A domain via transfection also rescues Ca2+ signaling. These results suggest that dysferlin -- specifically its C2A domain -- stabilizes DHPR -RyR1 coupling to suppress Ca2+ leak and CICR, which is likely pathogenic. We also found a role for PKCα. (vii) PKCα concentrates at TJs. (viii) Dysferlin and PKCα co-immunoprecipitate. (ix) Targeting dysferlin’s C2A domain to TJs as a chimera with the C2 domain of PKCα increases its ability to rescue Ca2+ signaling. (x) Activation of PKCα with PMA suppresses abnormal Ca2+ signaling in injured dysferlin-null fibers. (xi) Inhibition of PKCα with Gö6976 induces abnormal Ca2+ signaling, including Ca2+ waves, in injured wild type fibers. These results suggest that dysferlin stabilizes DHPR-RyR1 coupling and suppresses Ca2+ leak by facilitating targeted phosphorylation by PKCα, but that activation of PKCα can compensate for dysferlin’s absence to shut down RyR1-mediated leak.Item The Assessment of Commercially Available In-Home Drug Disposal Product(2025-02-14) Vavaroutsos, Kacey; Tawde, Salonee; Ibrahim, Ahmed; Johnson, Chad, Ph.D.; Hoag, Stephen W.Item Optimizing In Vitro Permeation Testing and Extraction Methods for Endogenous Estradiol and Estriol: Addressing Donor Variability and Experimental Challenges(2024-12-06) Gundlapalli, Saipavani; Reginauld, Bianca; Stinchcomb, Audra L., 1966-The measurement of endogenous estradiol and estriol levels in the skin is crucial for understanding their physiological roles and therapeutic applications. In vitro permeation testing (IVPT) is a key method for studying substance diffusion through the skin, but it faces challenges such as maintaining sink conditions and intra-subject variability. The purpose of this study is to evaluate the permeation and retention of endogenous estradiol and estriol in human skin using IVPT and extraction methods. The results from this research will help to facilitate the development of personalized dermatological treatments tailored to individual skin characteristics, enhance the effectiveness of transdermal drug delivery systems, and inform the formulation of cosmetic products designed for anti-aging and skin hydration.Item Oncology Patient Perspectives on Cannabis Use for Medical Purposes Related to Cancer Diagnosis in Maryland(2024-12-09) Ezeofor, Lotanna; Sera, Leah; Simms, Alexandra; Couture, Leah; Duffy, Alison P.Item Utilizing a Vizient Clinical Database for a Cost Savings Project(2024-12-11) Buzgo, Evan; Williams, Carla, Pharm.D., B.C.P.S; Dicubellis, JosephItem Determination of % Water Content in Potassium Citrate by Using KF, Moisture Analyzer, and LOD(2024-12-06) Katkade, Akash Sunil; Brown, KeithItem A Multiscale and Machine Learning-Based Approach to Efficient HDX Prediction(2024-12-06) Devarakonda, Akshatha; Wintrode, Patrick L.Item Impact of novel ERK1/2 signaling modulators on AP-1 proteins involved in airway smooth muscle cell proliferation relevant to airway remodeling in asthma(2024-11-13) Jateng, Danielle; Deshpande, Deepak; Pogash, Sarah; Fletcher, Steven; Shapiro, Paul, Ph.D.Item Improving Glycemic Control in Type 2 Diabetes: A Comparison of In-Person vs. Telehealth Diabetes Education(2024-12-09) Orenuga, AbiolaItem Comprehensive analysis of metabolites and biomarkers in lung using MALDI-MSI(2024-10-25) Andrews, William Temple; Oglesby, Amanda G.; Wilks, Angela; Farese, Ann M.; MacVittie, Thomas J.; Kane, Maureen A.Item APHA 2024 Cannabis(2024-10-27) Sealfon, Nicole; Barnes, Paris; Michel Dukes, Vanessa; Karslioglu, Rana; Shaya, Fadia T.Item Christian Pharmacists Fellowship International(2024-08-26)Item Expanding Vaccination Access in Underserved Communities Across Maryland Through a Collaborative Approach(2024-05-15) Brandt, NicoleItem Purification of paFur and Exploration of the Heme Regulation Mechanism over the phuS Gene(2024-07-26) Schindler, Isabella; Egoshi, Riki; Wilks, AngelaPseudomonas aeruginosa is a common bacteria that can cause various infections in the human body and survives in the body during chronic infections via iron from heme. The Wilks Lab is interested in finding ways to disrupt the transportation of heme to P. aeruginosa in order to cure infections. The PhuS protein is part of the heme uptake systems that affect heme delivery into P. aeruginosa and is known to be regulated by heme and iron. This project specifically focuses on finding the heme dependent transciptional regulator of the phuS gene promoter.Item Novel Next-generation Non-catalytic p38alpha/MK2 Immunomodulators with Endothelial-barrier-stabilizing and Anti-inflammatory Activity(2024-05-17) Tulapurkar, Mohan; Lugkey, Katerina; Shapiro, Paul, Ph.D.; Fletcher, Steven; MacKerell, Alexander D., Jr.; Luo, Wendy; Lal, Ritu; Hasday, Jeffrey D.We have previously identified a small three-ring molecule, UM101, targeted to the ED substrate-docking domain of p38alpha MAPK. UM101 modified p38alpha/MK2 signaling, stabilized endothelial barrier and reduced expression of proinflammatory genes. A next-generation analog with modifications on the first and third ring, Gen-1124, has improved anti-inflammatory and endothelial barrier-stabilizing activity, is lung protective in mouse models of influenza and ARDS, and is currently in a Phase II clinical trial in ARDS. To develop additional therapeutic candidates, we designed and synthesized UM101 analogs with modifications on the middle ring and tested the novel compounds for endothelial barrier- stabilizing and anti-inflammatory activity.Item Recruiting for Graduate Programs: One Size Does Not Fit All(2024-07-20) Johnson, Chad; Coop, Andrew; Sera, Leah; McCormick-Howell, Annamarie; San Juan, KristinaItem Teaching the Chemistry and Pharmacology of Psychedelics to Non-Scientists: Adaptation of PharmD Teaching Pedagogy for MS Students(2024-07-20) Coop, Andrew; Johnson, Chad; Sera, LeahItem Short-chain dehydrogenase/reductase 3 (DHRS3) deficiency results in altered patient retinoid profiles(2024-07-07) Yu, Jianshi; Williams, Christina; Liu, Tian; Pilli, Nageswara; Trainor, Paul A.; Moise, Alexander A.; Wilkie, Andrew; Kane, Maureen A.Item Longitudinal Treatment Pathways Following Opioid Use Disorder Diagnosis Among Commercially-Insured Beneficiaries in the U.S.(2024-07-01) Pathan, Uzma; Saini, Jannat; DiPaula, Bethany; Ehret, Megan J.; Johnson, Abree; Qato, Danya; Rizk, John