Pharmacy and Pharmaceutical Sciences Commons^™

Host-Derived Interleukin-1Α Drives Tumor Immunosuppression By Reprogramming Tumor-Associated Myeloid Cells, Manikanda Raja Keerthi Raja, Gourab Gupta, Grace Atkinson, Katie Kathrein, Alissa R. Armstrong, R. Michael Gower, Igor Roninson Ph.D., Eugenia Broude, Mengqian Chen Ph.D., Hao Ji, Chang-Uk Lim, Hongjun Wang, Daping Fan, Peisheng Xu Ph.D., Hexin Chen

Faculty Publications

Myeloid cells are highly heterogeneous and play key roles in establishing an immunosuppressive tumor microenvironment (TME), but the mechanisms controlling their differentiation remain unclear. Using orthotopic murine breast cancer models, we investigated how interleukin-1α (IL-1α) influences this process. Deletion of host Il1α resulted in rejection of transplanted tumors. Single-cell RNA sequencing identified CX3CR1⁺ macrophages as the main source of IL-1α in the TME. Il1α deficiency disrupted monocyte–macrophage differentiation, reducing CX3CR1⁺ macrophages and increasing iNOS⁺ macrophages. Myeloid cells from Il1α⁻/⁻ hosts induced lower PD-1 and CTLA-4 expression in co-cultured CD8⁺ T cells than those from wild-type hosts. CellChat analysis showed …

Anoikis Resistance And Metastasis Of Ovarian Cancer Can Be Overcome By Cdk8/19 Mediator Kinase Inhibition, Mehri Monavarian, Resha Rajkarnikar, Emily Faith Page, Asha Kumari, Liz Quintero Macias, Felipe Massicano, Nam. Y. Lee, Sarthak Sahoo, Nadine Hempel, Mohit Kumar Jolly, Lara Ianov, Elizabeth Worthey, Abhyudai Singh, Igor Roninson Ph.D., Eugenia Broude Ph.D., Mengqian Chen Ph.D., Karthikeyan Mythreye

Faculty Publications

Anoikis resistance, or evasion of cell death triggered by matrix detachment, is a hallmark of cancer cell survival and metastasis. We showed that repeated exposure to suspension stress followed by recovery under attached conditions leads to development of anoikis resistance. The acquisition of anoikis resistance was associated with enhanced invasion, chemoresistance, and immune evasion in vitro and distant metastasis in vivo. This acquired anoikis resistance was not genetic, persisting for a finite duration without detachment stress, but was sensitive to CDK8/19 mediator kinase inhibition that could also reverse anoikis resistance. Transcriptomic analysis revealed that CDK8/19 kinase inhibition induces bidirectional transcriptional …

Cognitive Function And Hypertension, Natalia Motzko Noto, Betsi Reinosa Corrada, Lisa S. Robison, Robert Charles Speth

Faculty Proceedings, Presentations, Posters, Speeches, Lectures, etc.

Given the brain’s high energy demands, the blood supply to the brain is critical for its function. Hence the importance of an intact brain vascular system to adequately perfuse the brain to sustain cognitive function. Given the damage to the vascular system that ensues from hypertension, it is a foregone conclusion that chronic hypertension will lead to cognitive impairments that can ultimately lead to dementia. Despite this logical connection, it was not until the 1990’s that the association between hypertension and dementia began to be made. And, it was not until 2000 that the first definitive connection between hypertension and …

Molecular Survival Strategies Against Kidney Filtration: Implications For Therapeutic Protein Engineering, William Heaps, Anna Elise Packard, Kristina M. Mccammon, Tyler P. Green, Joseph P. Talley, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

The glomerular filtration barrier poses a significant challenge for circulating proteins, with molecules below ~60–70 kDa facing rapid renal clearance. Endogenous proteins have evolved sophisticated evasion mechanisms including oligomerization, carrier binding, electrostatic repulsion, and FcRn-mediated recycling. Understanding these natural strategies provides blueprints for engineering therapeutic proteins with improved pharmacokinetics. This review examines how endogenous proteins resist filtration, evaluates their application in protein engineering, and discusses clinical translation including established technologies (PEGylation, Fc-fusion) and emerging strategies (albumin-binding domains, glycoengineering). We address critical challenges of balancing half-life extension with tissue penetration, biological activity, and immunogenicity—essential considerations for the rational design of next-generation …

Treatment For Women With Mental Health Disorders Associated With Reproductive Health: An Opportunity For Interprofessional Collaboration, Ellen Modlin Phd, Otr/L, Bcp, Caps, Deana Goldin Phd, Dnp, Arnp, Fnp-Bc, Pmhnp-Bc

Journal of Interprofessional Practice and Collaboration

Abstract

Purpose: This article proposes an opportunity for interprofessional collaboration between mental health practitioners (MHPs) and occupational therapy practitioners (OTPs) for the treatment of women experiencing mental health disorders (MHDs) associated with reproductive health (RH) changes throughout the lifespan. This collaborative approach have the potential to optimize women’s health care and mitigate the risk of fragmented care, as these conditions are highly complex.

Method: Peer- reviewed literature from mental health and occupational therapy (OT) research was reviewed and summarized. The search focused on the barriers and potential opportunities for collaboration between MHPs and OTPs in women affected with MHDs associated …

Direct Effects Of Capsaicin On Voltage-Dependent Calcium Channels Of Mammalian Skeletal Muscle, Dmytro Isaev, Tatiana Prytkova, Badarunnisa Mohamed, Mohamed Omar Mahgoub, Keun-Hang Susan Yang, Murat Oz

Pharmacy Faculty Articles and Research

Capsaicin, a naturally occurring polyphenol, is known to affect energy expenditure and muscle fatigue and modulate contractions in skeletal muscle. The L-type Ca²⁺ channels are known to be an important ion channel involved in the various muscle functions and the effect of capsaicin on the skeletal L-type Ca²⁺ channels is currently unknown. In this study, the effects of capsaicin and capsaicin analogs on depolarization-induced Ca²⁺ effluxes through L-type Ca²⁺ channels in transverse tubule membranes from rabbit skeletal muscle and L-type Ca²⁺ currents recorded using the whole-cell patch clamp technique in rat myotubes were examined. Capsaicin, …

Impact Of Apitegromab On Motor Function In Spinal Muscular Atrophy, Jordyn Linfield, Ashley Jacob, Haylee Whyde, Owen Fox, Kaitlyn Bowden, Connor Dains, Brenna Hissong, Manoranjan D'Souza

Pharmacy and Wellness Review

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder characterized by the progressive loss of alpha motor neurons in the anterior horn of the spinal cord, leading to muscle weakness, atrophy, and impaired motor function.¹ SMA remains an extensive and difficult-to-treat condition, with only three disease-modifying therapies currently available to patients. A new investigational agent with a unique mechanism of action, apitegromab (SRK-015), has shown promising results in recent clinical trials. The safety and efficacy of apitegromab in patients with SMA have been explored in several clinical trials, with the TOPAZ and SAPPHIRE studies being the most notable. This …

Fda Approval Of The Eversense 365 Continuous Glucose Monitoring System: A New Era In Long-Term Glucose Monitoring, Kiley Devoll, Alexander Defranco, Kennedy Kosikowski, Anna Spalvieri, Macy Davis, Connor Dains, Brenna Hissong, Emily Eddy

Pharmacy and Wellness Review

Eversense 365 is an implantable continuous glucose monitoring (CGM) system designed to provide accurate glucose measurements for up to 365 days. Current clinical guidelines recommend CGM use for patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), with evidence demonstrating benefit in patients with T2DM regardless of concurrent insulin use. Healthcare providers play a key role in patient education and are well-positioned to support the adoption of long-term CGM technologies, including Eversense 365. The safety and efficacy of the 365-day CGM have been evaluated across a series of clinical trials, which demonstrate clinically meaningful improvements in …

Fda Policy Shift On Clinical Efficacy Study Requirements For Monoclonal Antibody Biosimilars, Rileigh Rahrig, Madilyn Paphanchith, Allie Honigford, Daniella Egbujor, Haley Brown, Jenny Magana Figueroa, Connor Dains, Brenna Hissong, Kyle W. Parker

Pharmacy and Wellness Review

Biologic products are widely used in the treatment of various disease states, including rheumatoid arthritis, inflammatory bowel disease, cancers, and genetic diseases. These products are derived from proteins and genes produced by living organisms and are subsequently used to treat specific disease states. Due to the complexity of biological products, the costs of research and production are high. Currently, the United States approval pathway requires extensive testing for biologics to be designated as biosimilars, meaning there are no clinically meaningful differences in safety or purity of their active components. These required tests can be redundant, as biosimilars are developed using …

P-78. Susceptibility Of Omadacycline In Bone And Joint Infections: Pathogen Susceptibility And Regimen Decisions From An Ongoing Randomized Controlled Trial, Amy Y. Kang, Evelyn A. Flores, Donna Phan Tran, Buchen (Olivia) Han, Isabel Payan, Guarina Garcia Delgado, Loren G. Miller

Pharmacy Faculty Articles and Research

Background   Treatment of Bone and joint infections (BJIs) with oral antibiotics may have benefits compared to IV therapy. Yet oral treatment options may be limited by lack of options due to antibiotic-resistant pathogens and tolerability concerns. Omadacycline has in vitro activity against common BJI pathogens, including MRSA and most Enterobacterales. However, real-world susceptibility data and implications for oral therapy are limited.   Methods

We conducted a descriptive analysis of data from adult patients enrolled to date in an open-label, randomized controlled trial of comparing omadacycline-containing antibiotic regimen vs. standard of care (SOC) antibiotics for BJIs. Omadaycline susceptibility was assessed on available …

686. Antibiotic Prescribing For Urinary Tract Infections In Outpatient Settings: A Multicenter Assessment Based On The Five Ds Of Stewardship, Amy Y. Kang, Oliver Tan, Sunwoo Oh, Nikki Derleth, Megan Shieh, Helen Vu, Inna Tagarino, Audrey Harrington, Deborah Kupferwasser, Loren G. Miller

Pharmacy Faculty Articles and Research

Background   Urinary tract infections (UTIs) are a leading cause of outpatient antibiotic use. Prior studies have documented inappropriate prescribing during outpatient UTI visits, but few have assessed intervention opportunities using a structured stewardship framework. We evaluated UTI prescribing practices in a healthcare system using the Five Ds framework: Diagnosis, Drug, Dose, Duration, and De-escalation.   Methods

We conducted a retrospective study across 4 medical centers and > 20 outpatient clinics within the Los Angeles County Department of Health Services, the second largest U.S. safety net healthcare system. To ensure adequate representation across sites while maintaining feasibility for manual chart review, we reviewed …

Grover's Disease: A Review Of The Current Treatment Options, Dustin Ross, Dmsc, Mph, Pa-C

Lynchburg Journal of Medical Science

Grover’s disease, also known as transient acantholytic dermatosis, is an uncommon dermatologic condition characterized by pruritic papulovesicular eruptions that predominantly affect the trunk of older adults. Although the disease is often self-limited, it may significantly impair quality of life. This review summarizes treatment options and emerging therapies for Grover’s disease reported in the literature since 2019. A comprehensive search of PubMed and MEDLINE identified 1,068 records, of which thirteen publications met inclusion criteria, including one systematic review, one narrative review, one nonrandomized controlled study, nine case reports, and one fact sheet, representing a total of 337 patients. The literature demonstrates …

Physician Assistants And The Medical Science Liaison Role: Expanding Career Pathways Beyond Clinical Practice, Michael Filsinger

Lynchburg Journal of Medical Science

ABSTRACT

The purpose of this article is to examine how physician assistants can transition into Medical Science Liaison roles within the pharmaceutical and biotechnology industries. Growing interest in nonclinical career pathways has prompted more physician assistants to explore opportunities in medical affairs, yet many remain uncertain about the qualifications, expectations, and academic preparation associated with these positions. A focused literature review was conducted to evaluate the competencies required for Medical Science Liaison roles, the barriers clinician applicants often encounter, and the strategies that may support successful transition into industry-based careers. Findings show that physician assistants possess relevant strengths such as …

Structural Basis For The Subtype-Selectivity Of KCa2.2 Channel Activators, Young-Woo Nam, Alena Ramanishka, Yang Xu, Rose Marie Haynes Yasuda, Joshua A. Nasburg, Dohyun Im, Meng Cui, K. George Chandy, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance (K_Ca2.2) and intermediate-conductance (K_Ca3.1) Ca²⁺-activated K⁺ channels are gated by a Ca²⁺-calmodulin dependent mechanism. NS309 potentiates the activity of both K_Ca2.2 and K_Ca3.1, while rimtuzalcap selectively activates K_Ca2.2. Rimtuzalcap has been used in clinical trials for the treatment of spinocerebellar ataxia and essential tremor. We report cryo-electron microscopy structures of NS309-bound K_Ca2.2 and K_Ca3.1, in addition to structures of rimtuzalcap-bound K_Ca2.2 and mutant K_Ca3.1_R355K. The different conformations of calmodulin and the cytoplasmic HC helices in the …

Physiologically Based Pharmacokinetic Modeling Of Acetaminophen In A Preterm Neonate Population, Sonia Sharma

Selected Full-Text Dissertations 2020-

Extremely preterm neonates are a pharmacologically vulnerable group due to their immature organ function and rapid developmental changes, which complicate optimal drug dosing. This thesis introduces a comprehensive physiologically based pharmacokinetic (PBPK) model for acetaminophen (APAP) tailored to this population, incorporating mechanistic ontogeny equations for key sulfotransferase (SULT) enzymes SULT1A1, SULT1A3, SULT1B1, and SULT2A1 developed from a unique dataset of pediatric liver samples. The PBPK model was calibrated and validated using observed pharmacokinetic data from neonates, infants, and children, demonstrating high predictive accuracy across developmental stages. By applying virtual twin simulations, the model was used on a nationwide children's hospital …

Reducing Healthcare Spending With Pharmacist Driven Icg Allocation, Rachel W. Wong, Calvin Le, Vanessa Sifuentes, Faith Rutherford, Grace Desrochers, Zuhair Ali, Mike K. Liang

Gulf Coast Division GME Research Day 2026

No abstract provided.

A Flupirtine Benzyl Carbamate Improves Neurocognitive Deficits And Molecular Pathology In The Cln6nclf Mouse, Victoria Chaoul, Omar Shmoury, Ramy Alam, Sara Saab, Joelle Makoukji, Lynn Al Aridi, Nadine J. Makhoul, Jihane Soueid, Angelica V. Carmona, Princess Simeon, Paul C. Trippier, Rose-Mary Boustany

Journal Articles: Pharmaceutical Sciences

Neuronal ceroid lipofuscinosis type 6 (CLN6) is a fatal, autosomal recessive neurodegenerative disorder characterized by cognitive/motor impairment, vision loss, as well as neuronal loss and gliosis in the brain, and premature death. Onset typically occurs in childhood. No approved pharmacological treatments exist that halt or reverse disease progression. A novel flupirtine benzyl carbamate was orally administered to male and female Cln6^nclf mice from 4 to 28 weeks of age to evaluate its neuroprotective and antispastic effects. Drug treatment produced significant, sex-dependent phenotypic improvements. Treated mice of both sexes exhibited reduced hindlimb spasticity, but only treated males demonstrated diminution in …

Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao

Pharmaceutical Sciences (PhD) Dissertations

A significant problem faced in oncology is the lack of chemotherapeutic agents that are tumor site-specific, resulting in reduced therapeutic efficacy and unintended infliction of harm to surrounding healthy tissues and cells that often lead to serious side effects. Current strategies being explored to circumvent this issue aim to refine delivery of  chemotherapeutic agents specifically to tumor sites, which may be achieved via conjugation of these agents to biomarker-specific ligands. This forms the foundation of ligand-targeted drug delivery. Among different breast cancers, treatment of the triple-negative breast cancer (TNBC) subtype has been particularly challenging, largely due to the absence of …

Amyloid Β-Cholesterol Interplay: Removal Of Cholesterol From The Membranes To Catalyze Aggregation And Amyloid Pathology, Rishiram Baral, Ruan Van Deventer, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The interplay between the cholesterol metabolism and assembly of Aβ42 (the 42-residue form of the amyloid-β peptide) peptides in pathological aggregates is considered one of the major molecular mechanisms in the development of Alzheimer's disease (AD). Numerous in vitro studies led to the finding that high cholesterol levels in membranes accelerate the production of Aβ aggregates. The molecular mechanisms explaining how cholesterol localized inside the membrane bilayer catalyzes the assembly of Aβ aggregates above the membrane remain unknown. We addressed this problem by combining different AFM modalities, including imaging and force spectroscopy, with fluorescence spectroscopy. Our combined studies revealed that …

In Vitro Dihalobenzene Nephrotoxicity In Isolated Kidney Cells, Jana Ahmed Sherif

Theses, Dissertations and Capstones

Brominated and chlorinated benzenes are common industrial chemicals linked to kidney injury. This study evaluated the nephrotoxicity of several mono- and dihalogenated derivatives using isolated kidney cells from male Fischer 344 rats. LDH release and trypan blue exclusion were measured after 30- and 60-minute exposures to 0.25–1.0 mM to test compounds. Toxicity increased with increased concentration and longer times. Mixed-halogen bromobenzenes, particularly 1-bromo-4-chlorobenzene, showed one of the highest toxicity levels, while 1,4dichlorobenzene was the most toxic chlorobenzene. Antioxidants (glutathione, ascorbate, and αtocopherol) markedly reduced injury, indicating oxidative mechanisms play a role in toxicity. cytochromes P450 (CYP) inhibitors (piperonyl butoxide and …