Characterization Of Novel Arrhythmogenic Patterns Arising Secondary To Heterogeneous Expression And Activation Of Nav1.8, Zhong-He Zhang, Hector Barajas-Martinez, Hong-Yi Duan, Guo-Hua Fan, Hong Jiang, Charles Antzelevitch, Hao Xia, Dan Hu

Department of Medicine Faculty Papers

Background: Previous studies suggested that SCN10A/Nav1.8 may influence cardiac electrophysiology and the susceptibility to cardiac arrhythmias. Notably, the expression of SCN10A is not uniform, showing variable expression in each cardiac chamber. The present study aims to explore the functional significance of Nav1.8 expression among different cell types present in the ventricular myocardium.

Methods: The effect of the specific Nav1.8 blocker, A-803467, on action potential was recorded from epicardial, mid-myocardial (M cells) and Purkinje tissue slices isolated from the canine left ventricle using standard microelectrode techniques and on late sodium current from Purkinje cells using patch-clamp techniques.

Results: A-803467 treatment …

The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …

Small Molecule B-Raf Inhibitors As Anti-Cancer Therapeutics: Advances In Discovery, Development, And Mechanistic Insights, Yamile Abuchard Anaya, Ricardo Pequeno Bracho, Subhash Chauhan, Manish K. Tripathi, Debasish Bandyopadhyay

School of Medicine Publications

B-RAF is a serine/threonine kinase that plays a crucial role in the MAPK signaling pathway, regulating cell proliferation and survival. Mutations in B-RAF, particularly V600E, are associated with several malignancies, including melanoma, colorectal cancer, and non-small cell lung cancer, making it a key therapeutic target. The development of B-RAF inhibitors, such as Vemurafenib, Dabrafenib, and second-generation inhibitors like Encorafenib, has led to significant advancements in targeted cancer therapy. However, acquired resistance, driven by MAPK pathway reactivation, RAF dimerization, and alternative signaling pathways, remains a major challenge. This review explores the molecular mechanisms of B-RAF inhibitors, their therapeutic efficacy, and resistance …

Glucagon-Like Peptide-1 Receptor Agonists: Exciting Avenues Beyond Weight Loss, Lalitha Sundararaman, Divakara Gouda, Anil Kumar, Sumithra Sundararaman, Basavana Goudra

Department of Anesthesiology Faculty Papers

The last two decades have proffered many remarkable choices in managing type 1 and type 2 diabetes mellitus. Leading the list are glucagon-like peptide-1 receptor agonists (GLP1RAs), the first of which, exenatide, was approved by the FDA in 2005. Two other major classes of drugs have also entered the market: dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly known as gliptins and approved in 2006, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, with the first approval occurring in 2013. These drugs have revolutionized the treatment of diabetes. Additionally, on the horizon, the once-weekly basal insulin analog insulin icodec and the once-weekly combination of insulin icodec …

Prodrug Activation In Malaria Parasites Mediated By An Imported Erythrocyte Esterase, Acylpeptide Hydrolase (Apeh), Sesh A. Sundararaman, Justin J. Miller, Ellora C. Daley, Kelsey A. O'Brien, Paulina Kasak, Abigail M. Daniels, Rachel L. Edwards, Kenneth M. Heidel, Darean A. Bague, Madeleine A. Wilson, Andrew J. Koelper, Elexi C. Kourtoglou, Alex D. White, Sloan A. August, Georgia A. Apple, Regis W. Rouamba, Anthony J. Durand, John J. Esteb, Florian L. Muller, R. Jeremy Johnson, Geoffrey C. Hoops, Cynthia S. Dowd, Audrey R. Odom John

College of Health Professions Faculty Papers

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards et al., Sci. Rep. 7, 8400 (2017)]. However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme of multiple …

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …

Screening For Penicillin G Acylase (Pga)-Producing Bacteria And Gene Cloning Using Degenerate Oligonucleotide Primed-Pcr, Masdalifah Masdalifah, Sri Rezeki Wulandari, Gabriela Christy Sabbathini, Maria Ulfah, Dini Achnafani, Ahmad Wibisana, Feronika Heppy Sriherfyna, Is Helianti, Niknik Nurhayati

Makara Journal of Science

The growing concern over antibiotic resistance has driven global efforts to explore innovative solutions, including the use of Penicillin G acylase (PGA) to produce semisynthetic β-lactam antibiotics. This study screened four potential in-tracellular PGA-producing bacteria: Alcaligenes faecalis InaCC B444 (AfPGA), Kluyvera cryocrescens InaCC B850 (KcPGA), Providencia rettgeri InaCC B25 (Pr25PGA), and P. rettgeri InaCC B466 (Pr466PGA). Penicillin G Acylase encoding genes (pgas) were isolated from them using a Degenerate Oligonucleotide Primed-PCR (DOP-PCR) approach and sequenced. Microbiological assays confirmed all tested crude extracts to exhibit inhibitory effects. Penicillin G was used for evaluating hydrolytic activity and 6-Amino Penicillanic Acid (6-APA) coupled …

A Case Of Turmeric-Induced Hepatotoxicity With Hyperferritinemia, Nina R. Spitofsky, Albert A. Huang, Aria Jalalian, Stefanie Gallagher, Scott Fink

Department of Medicine Faculty Papers

Introduction: We present the first published case of turmeric-associated drug-induced liver injury (DILI) accompanied by significant ferritin elevation. Case Presentation: Our patient, a 59-year-old female with DILI caused by long-term ingestion of oral turmeric supplements, presented with painless jaundice on an annual exam. The patient’s liver function tests exhibited a hepatocellular pattern and hyperferritinemia (>2,000 ng/dL). Additional testing was negative except for heterozygosity for the H63D allele associated with hemochromatosis. A liver biopsy indicated acute hepatitis without fibrosis or stainable iron. Conclusion: Upon discontinuation of the supplement, liver enzymes normalized within a month. This case highlights the potential for …

Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato

Kimmel Cancer Center Faculty Papers

The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression …

Exploring Cucurbitacin D'S Protective Mechanism Against Benzo[A]Pyrene-Induced Liver Injury Through Nrf2 Activation, Shabnam Malik, Mohammed Sikander, Anyssa Rodriguiez, Daniel Zubieta, Debanhi Esparaza, Fathi T. Halaweish, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

Research Symposium

Background: Numerous studies have established a strong association between hepatocellular carcinoma (HCC) and various co-morbidity factors, including smoking. Tobacco smoke is a significant source of benzo[a]pyrene, a highly carcinogenic compound known to cause liver damage. Cucurbitacin, a triterpene with diverse biological activities, exhibits antioxidant, antiinflammatory, and anticancer effects. However, its hepatoprotective properties have not been thoroughly investigated. In this study, we aimed to evaluate the hepatoprotective effects of cucurbitacin D, a novel analog of cucurbitacin, against liver injury induced by benzo[a]pyrene in human HepG2 cells.

Method: To investigate the hepatoprotective effect of cucurbitacin D against benzo[a]pyreneinduced liver damage, proliferation, clonogenicity, …

Evaluating The Potential Of Herbal Extracts As Treatment In Immune Thrombocytopenia: A Review Of Evidence And Limitations, Russell Wiggins, Jihoo Woo, John Cauba, Shizue Mito

Research Symposium

Immune thrombocytopenia, formerly idiopathic thrombocytopenia purpura (ITP), is an autoimmune disease characterized by the depletion of platelets below 100,000/µl when other causes of thrombocytopenia have been ruled out. It is associated with several infectious pathologies, disease states, and as a known side effect and complication of several drugs and chemotherapies. Standard treatment calls for glucocorticoid mediated immunosuppression, intravenous immunoglobin transfusion, platelet stimulation, platelet transfusion, and splenectomy in instances of chronic and severe disease. While standard treatments are often effective, some cases prove resistant, and more commonly, some patients are unable to tolerate standard treatment protocols or opt out of surgical …

Improving Niclosamide's Effectiveness In Cancer Therapy: Advances In Drug Modification And Delivery, Russell Wiggins, Jihoo Woo, Shizue Mito

Research Symposium

The property of niclosamide to inhibit multiple cancer-related pathways has made it a promising candidate for the treatment of various cancers. However, poor bioavailability and solubility have significantly restricted its clinical application. This literature review explores various strategies that enhance the bioavailability and efficacy of Niclosamide through the development of Niclosamide derivatives and the utilization of drug delivery systems. We also briefly discuss Niclosamide’s suspected mechanisms of action in several cancer related pathways. Derivatives such as Niclosamide Ethanolamine (NEN) and Niclosamide Piperazine (NPP) have demonstrated improved pharmacokinetic properties, including increased solubility and bioavailability, without compromising anticancer activity. Importantly, these formulations …

Association Of Inflammatory Biomarkers With New Functional Morbidity At Hospital Discharge In Children Who Survive Severe Sepsis, Mallory Perry-Eaddy, Walter Faig, Martha Curley, Scott Weiss

Department of Pediatrics Faculty Papers

OBJECTIVE: New functional morbidity is common in critically ill children who survive sepsis; yet, the underlying biological mechanisms, particularly the impact of inflammation, remain unknown. We sought to test the hypothesis that increased levels of inflammatory biomarkers during the acute phase of pediatric sepsis are associated with new functional morbidity at hospital discharge.

METHODS: We conducted a post hoc secondary analysis of the MitoPSe clinical study, including N = 119 critically ill children who survived sepsis. Data collected included demographic and clinical variables and 31 inflammatory biomarkers collected at three distinct timepoints (within days 1-2 of PICU admission, days 3-5, …

The Role Of The Female Reproductive Cycle In Social Communication And Relevance To Mental Health, Julissa Amaro Castillo, Fernando Dominguez, Ariana Hinojosa, Giselle Padilla, Mario Gil

Research Symposium

The female reproductive cycle is characterized by fluctuating hormones, including estrogens and progesterone, that are involved in reproductive health; however, they have also been linked to disorders like Premenstrual syndrome (PMS), Premenstrual Dysphoric Disorder (PMDD), mood swings, depression and others. The goal of this study is to use the Syrian hamster (Mesocricetus auratus) as an animal model to examine the influence of the reproductive cycle and hormones on behavior. Scent-marking activity known as flank marking is exhibited by territorial or sociable animals. In essence, animals mark their territory or convey information such as reproductive status by rubbing their flanks or …

Effects Of Arginine-Vasopressin In The Brain On Cardiovascular Function In A Psychosocial Stress Animal Model, Esmeralda Lopez-Garcia, Ariana V. Hinojosa, Esperanza I. Alaniz, Fernando Dominguez, Giselle Padilla, Mario Gil

Research Symposium

Background: Psychosocial stress impacts cardiovascular health, increasing the risk of events like myocardial infarction (MI), stress cardiomyopathy, and neuropsychiatric disorders, including Major Depressive Disorder (MDD) and Anxiety. However, our understanding of the biological mechanisms that connect psychosocial stress with negative cardiovascular and psychological outcomes remains incomplete. Arginine-vasopressin (AVP) is linked to both mental and physical health by regulating social behavior, blood pressure, and anxiety-related behaviors. This study investigates the potential cardioprotective effects of the neuropeptide AVP, in an effort to generate evidence that it may strengthen heart function and lessen the severity of adverse cardiovascular events caused by stress, brain …

Implementation Of Staff Education On Suicide Prevention, Julianne Ji, Hannah Cryder, Trista Joy, Isabel Pfingston, Jaylen Wilson, Kelsey Crosby, Ashlyn Mulcahey

Nursing Leadership in Community Engagement Projects

Implementation of Staff Education on Suicide Prevention

Kelsey Crosby, Hannah Cryder, Julianne Ji, Trista Joy, Ashlyn Mulcahey, Isabel Pfingston, and Jaylen Wilson

School of Health Sciences, Seattle Pacific University

NUR4153: Nursing Leadership in Community Engagement

Dr. Bomin Shim

February 26, 2025

Implementation of Staff Education on Suicide Prevention

Our group, consisting of seven nursing students, partnered with an agency dedicated to supporting individuals in recovery from addictions of all forms, including substance use, gambling, and alcohol dependence. The agency focuses on helping them reach their full potential, minimize relapse, and maintain recovery. Elements of the agency’s work include providing two …

Synthesis Of Medicinally Privileged Spiro-Β-Lactams, Debasish Bandyopadhyay, Reinaldo Mendes, Subhash C. Chauhan

Research Symposium

Background: Four-membered cyclic amide, commonly known as β-lactam, has been playing a crucial role in drug discovery research since its discovery by Alexander Fleming in 1928 from Penicillium notatum. The β-lactam antibiotics are broadly effective against several bacterial infections through acylating the transpeptidase involved in cross-linking peptides to form peptidoglycan or periplasmic murein, which is a fundamental constituent of the bacterial cell wall for both the gram-positive (ten or more layers) and gram-negative (one or two layers) bacteria. Although for more than eight decades, β-lactams have been recognized as antibiotics, later, other medicinal activities of β-lactam derivatives have been …

Exploring The Effects Of Serotonin And Ssris On The Neurological, Behavioral, And Cardiovascular Systems Under Induced Stress –Using The Animal Model Of The Syrian Hamster, Ariana V. Hinojosa, Esperanza I. Alaniz, Esmeralda Lopez-Garcia, Giselle Padilla, Fernando Dominquez, Mario Gil

Research Symposium

Background: Serotonin is a neurotransmitter that has been found to have a wide range of effects on not just the neuropsychological processes but has also been found to exert effects outside the central nervous system (CNS); regulating numerous biological processes, such as metabolism, gastrointestinal system, reproductive function, and even the cardiovascular system. However, there is still a limited understanding of how serotonin affects all these systems due to its complexity and ability to regulate homeostasis. This project aims to create a stronger foundation of knowledge about serotonin and its influence on the interaction between the CNS, behavior, and cardiac function …

Long-Term Safety And Comparative Efficacy Of Il-17 Inhibitors In Treating Ankylosing Spondylitis, Alyssa L. Sepulveda, Yolanda V. Gutierrez, Ronald A. Shaju

Research Symposium

Background:
Ankylosing Spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, characterized by spinal stiffness, sacroiliitis, and potential vertebral fusion. While nonsteroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor (TNF) inhibitors are first-line treatments, IL-17 inhibitors, such as secukinumab and ixekizumab, are used in patients with inadequate response or contraindications to TNF inhibitors. These targeted therapies address IL-17’s role in driving inflammation and structural damage in AS.

Methods:
A systematic review was conducted using PubMed, Science Direct, and Cochrane to identify studies published between 2000 and 2025. Keywords included “Ankylosing spondylitis” and “IL-17 inhibitors” and “efficacy.” Inclusion criteria …

Epigenetic Landscapes Of Aging In Breast Cancer Survivors: Unraveling The Impact Of Therapeutic Interventions-A Scoping Review, Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy L Shaver, Victoria Seewaldt, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting …