Pharmacology, Toxicology and Environmental Health Commons^™

An Observational Study Of The Effect Of Concomitant Levetiracetam On Apixaban Concentrations In A Hospital Cohort, Chazmyn Riley, Kevin Lam, Cristina Micale, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the lack of evidence of a mechanism-based drug interaction, some professional organizations have advised caution coadministering apixaban and levetiracetam. Eligible patients taking apixaban with or without levetiracetam for any indication for at least 72 h were screened from the electronic medical records. Plasma samples from 77 patients were retrieved from salvaged clinical blood collections. Apixaban minimum and maximum concentrations (Cmin and Cmax) were compared using descriptive statistics in R. While the median Cmin and Cmax appear to be marginally elevated, there were no apparent differences relative to apixaban alone. These findings suggest no apparent interaction of levetiracetam and support …

Toxic Relationships: Characterization Of A Putative Virally Encoded Toxin In The Thermophilic Archaeal Fusellovirus Ssv1, Jonathan C. Abshier, Patrizia L. Alpapara, Guasåli Tomokane, Kenneth M. Stedman

Center for Life in Extreme Environments Publications

Mechanisms for the maintenance of chronic viruses are poorly understood, particularly for archaeal viruses. Here, we identify the product of Sulfolobus spindle-shaped virus 1 (SSV1) ORF a291 as a putative virally encoded toxin required for growth inhibition but dispensable for viral replication and virion production. Viruses lacking ORF a291 replicated their genomes and formed morphologically normal spindle-shaped particles, yet failed to inhibit the growth of uninfected Saccharolobus solfataricus. Substitution of residues at a predicted N-terminal signal peptide cleavage site abolished growth suppression without affecting replication, suggesting that secretion is essential for toxin function. Despite primary sequence divergence among fusellovirus …

Loss Of Palmitoylation Impacts The Interaction Between The Organic Anion Transporting Polypeptide (Oatp) 1b1 And Oatp1b3., Cecilia E. Villanueva, Whitney M. Nolte, Priscilla Flores-Ascencio, Bruno Hagenbuch

Manuscripts, Articles, Book Chapters and Other Papers

The organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are hepatic transporters that mediate the uptake of numerous therapeutics like antibiotics and statins. Various post-translational modifications, eg, phosphorylation and glycosylation, have been shown to impact OATP1B1 and OATP1B3 function and localization. S-palmitoylation (also known as S-acylation or palmitoylation) is a reversible post-translational modification that adds palmitic acid (C16:0) to cysteine residues and can influence a protein's function, localization, and protein-protein interactions. In this study, we investigated and characterized palmitoylation in OATP1B1 and OATP1B3. Using site-directed mutagenesis and acyl-resin-assisted capture assays, residue Cys24 was identified as the palmitoylation site for both …

Environmental Mercury Alters Immune Pathways Linked To Autoimmune Risk In Mice Mirroring Humans, Maurgan Lee, Paul Stemmer, Randall Gill, Allen Rosenspire, Anil Aranha, Heather Gibson

Medical Student Research Symposium

Background and Purpose: Mercury is a pervasive environmental contaminant, and human epidemiologic studies have linked chronic low-level exposure to increased autoimmune disease-risk. Dysregulated lymphocyte activation and impaired signaling tolerance are central mechanisms in human autoimmunity. Protein phosphorylation governs lymphocyte differentiation and function, alterations in phosphoproteomic networks may represent a signature of immune disruption. This study evaluates how low dose mercury exposure modifies B and T cell abundance and intracellular signaling patterns in BALB/c and Diversity Outbred (DO) mice.

Methods: BALB/c and DO mice were exposed to low dose HgCl2 in their water for two weeks or provided standard water controls. …

P300/Cbp Inhibition With Inobrodib In Combination With Gilteritinib And Venetoclax Targets Leukemia Stem Cells In Epigenetic Mutant Aml, Melanie L. Goetz, Jennifer S. Romer-Seibert, Amanda M. Versace, Scott Kogan, Chetan Jeurkar, Robert L. Bowman, Nigel Brooks, Kris Frese, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Acute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult patients with AML and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and …

The Risk Of Bpa In B Lymphocyte-Mediated Autoimmunity, Mario J. Palacios

Senior Honors Theses

Autoimmune disorders disproportionately affect females, a bias largely attributed to estrogen's modulation of B lymphocyte development and tolerance. Bisphenol A (BPA), a common plastic monomer, shows estrogenic activity and acts as an endocrine disruptor and epigenetic modifier. This thesis examines how BPA may increase autoimmune risk by mimicking estrogen such that it can excite estrogen receptors which rescue autoreactive B lymphocytes from apoptosis. While direct research linking BPA to B lymphocyte-mediated autoimmunity is limited, understanding BPA’s course of action in B lymphocytes is critical for addressing the rising prevalence of autoimmune diseases and its possible link to the increased and …

Herbularyo (Folk Healer): An Herbal Medicine Card Game, Maryjane T. Magsino, Inah Marie Q. Rivera, Armando M. Guidote, Genejane M. Adarlo

Chemistry Faculty Publications

Herbularyo, a card game teaching about herbal plants (HPs), was created and evaluated as a viable educational card game based on Tuomisto and Aksela’s criteria. A quasi-experiment was performed on 81 Grade 8 students from a private high school and 50 Grade 11 from a public high school. Independent t-test revealed that the control group (CG) and experimental group (EG) (p=0.386), and EG1 (played ≤5) and EG2 (played >5) (p=0.681) are not comparable with each other. Paired t-test showed EG performed better (p=0.001) than CG (p=0.901) whereas ANCOVA showed that playing Herbularyo improved students’ information retention (p=0.006). EG1 and EG2 …

Reversible, Light-Controlled Inhibition Of Stim1-Mediated Calcium Signaling Using Photoswitchable Ml-9 Derivatives In Jurkat-Lucia Nfat Reporter T Cells, José L. Matute Gálvez

Honors Scholar Theses

Store-operated calcium entry (SOCE) through calcium release-activated

calcium (CRAC) channels is the dominant pathway for sustained Ca2+ influx in

non-excitable cells and is essential for T cell activation, driving downstream

signaling through the calcineurin-NFAT transcriptional axis. Dysregulation of

SOCE produces multi-systemic disease phenotypes, establishing that precise,

spatiotemporally controlled modulation of this pathway is a fundamental

therapeutic requirement. ML-9 is one of the only characterized small molecules

capable of targeting SOCE upstream at the level of STIM1 localization, but lacks

the selectivity, pharmacokinetic properties, and spatiotemporal control necessary

for therapeutic development.

This work describes the design, synthesis, and biological evaluation of …

Psychedelic Research In The Modern Day: Good Or Bad?, Shane Miller

Mechanical Engineering Student Research

This work is about the usage/safety of psychedelic substances, and I explain whether they are good or bad in terms of other drugs, such as alcohol.

A Methotrexate Dashboard: Integrating Mtxpk.Org Into The Electronic Health Record To Facilitate Model-Informed Care For Pediatric Patients Receiving High-Dose Methotrexate., Zachary L. Taylor, Nieko Punt, Chris Jenkinson, Bill Vidonish, Jennifer Young, Maureen M. O'Brien, Laura Ramsey

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: The MTXPK.org webtool facilitates model-informed supportive care and glucarpidase use in patients receiving high-dose methotrexate, but its reliance on manual data entry limits workflow integration. We aimed to highlight how translational informatics can advance, automate, and enhance the usability of clinical decision support tools by embedding MTXPK.org within the electronic health record (EHR).

METHODS: A human factors study with 6 clinical providers guided iterative prototype development. MTXPK.org was rebuilt within the EHR using a 3-tier architecture with Fast Healthcare Interoperability Resources-based data retrieval, automated pharmacokinetic modeling, and interactive visualization.

RESULTS: Two rounds of prototyping with task-based evaluations and contextual …

Role Of Na⁺/K⁺-Atpase And Sodium–Calcium Exchanger In Digitoxin-Induced Cytotoxicity In Triple Negative Breast Cancer Cells, Alyson Sotomayor Quispe, Marilyn Odom Phd

SPARK Symposium Presentations

Triple Negative Breast Cancer (TNBC) is characterized by the absence of estrogen, progesterone, and HER2 receptors, limiting targeted treatment options. Digitoxin, a drug used to treat heart failure and atrial fibrillation through Na⁺/K⁺-ATPase inhibition, has demonstrated anticancer effects in TNBC cells, including apoptosis via the NF-κB pathway. This study investigates whether the Na⁺/K⁺-ATPase and sodium–calcium exchanger contribute to the mechanism of action of digitoxin in TNBC cells. We hypothesize that these transporters mediate digitoxin-induced cytotoxic effects. To test this, MDA-MB-468 cells were treated with digitoxin, and protein localization and expression were analyzed using immunofluorescence and Western blot. Digitoxin treatment resulted …

Moderate-Temperature Hydrothermal Treatment Removes Detectable Dna And Antibiotic Resistance Genes From Municipal Sludge While Preserving Resource Value, R Sean Norman M.Sc., Ph.D., Mirza Isanovic, Gabrielle Kartzmark, Nicole Berge

Faculty Publications

Wastewater treatment plants (WWTPs) are key reservoirs of antibiotic resistance genes (ARGs), with municipal sludge containing high bacterial densities and diverse ARGs that may spread through land application. Hydrothermal treatment (HT) is a process that inactivates pathogens and stabilizes biomass, but its performance at moderate temperatures is less understood. We evaluated HT (100°C–250°C; 2–24 h) for degrading bacterial DNA and ARGs in dewatered municipal sludge. DNA was quantified by fluorometry, bacterial presence confirmed by 16S rRNA gene PCR, and ARGs profiled by qPCR targeting 84 clinically and environmentally relevant genes. HT up to 250°C produced modest carbon densification, high solids …

Moderate-Temperature Hydrothermal Treatment Removes Detectable Dna And Antibiotic Resistance Genes From Municipal Sludge While Preserving Resource Value, R. Sean Norman, Mirza Isanovic, Gabrielle Kartzmark, Nicole Berge

Faculty Publications

Wastewater treatment plants (WWTPs) are key reservoirs of antibiotic resistance genes (ARGs), with municipal sludge containing high bacterial densities and diverse ARGs that may spread through land application. Hydrothermal treatment (HT) is a process that inactivates pathogens and stabilizes biomass, but its performance at moderate temperatures is less understood. We evaluated HT (100°C–250°C; 2–24 h) for degrading bacterial DNA and ARGs in dewatered municipal sludge. DNA was quantified by fluorometry, bacterial presence confirmed by 16S rRNA gene PCR, and ARGs profiled by qPCR targeting 84 clinically and environmentally relevant genes. HT up to 250°C produced modest carbon densification, high solids …

Seafood, Mercury, And Human Health In Coastal South Carolina: Findings From A Community-Based Study, Russell Fielding, Julia Saltzman, Rylee-Jade Bean, Jenna Monroe, Theodore R. Them Ii

Honors College Faculty Publications

Mercury (Hg), an environmental pollutant, can harm human health. Seafood consumption is a major way that people are exposed to Hg and the analysis of human hair is a standard method to measure Hg exposure. This community-based study identified demographic and dietary factors associated with elevated Hg concentrations and health outcomes of individuals with elevated Hg concentrations throughout two coastal South Carolina (SC) counties. We collected hair samples (n = 85) at local barbershops and salons; participants completed an online survey with questions on demographics, diet, and health histories; and we analyzed hair samples using a DMA-80. Between 4.9–8.4% of …

Freshwater Quality For Recreation, Heather Nix, Masha Bokar

Forestry and Natural Resources

South Carolina has many water resources that provide tremendous opportunities for people to enjoy water-based recreational activities, such as swimming, boating, and fishing. Participation in these activities produces significant economic benefits and supports many jobs throughout the state. However, at times, water quality may be unsafe for immersion or skin contact due to high levels of pollutants, such as bacteria or cyanotoxins. It is important for people to be aware of potential concerns and understand methods for determining if a waterbody’s current conditions are likely to be safe for primary or secondary recreation.

In Vitro Pharmacological Evaluation Of Novel Cmpi Derivatives As Selective Positive Allosteric Modulators Of The Alpha4 Beta2 Nicotinic Acetylcholine Receptor, Josue Gaona, Nataly Sanchez, Wilder Felix, Nathalia Menegasso, Brisa Cea, Ganesh Thakur, Ayman K. Hamouda

School of Medicine Student Publications and Presentations

Nicotinic acetylcholine receptors (nAChRs) contribute to the pathogenesis of neurodegenerative diseases such as Parkinson’s disease (PD), where degeneration of dopaminergic and cholinergic neurons disrupts neurotransmission. The (α4)₃(β2)₂ nAChR subtype is expressed on affected neuronal populations and represents a promising therapeutic target. Positive allosteric modulators (PAMs) may enhance receptor function while preserving endogenous signaling. We evaluated chemical derivatives of CMPI [3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl)isoxazol] as selective PAMs of (α4)₃(β2)₂ nAChRs. Two-electrode voltage-clamp recordings were performed in Xenopus laevis oocytes expressing defined receptor stoichiometries to assess potentiation and generate dose–response curves. Cytotoxicity was assessed in HEK cells using the MTT assay. Substitutions at the pyrazole …

Comparison Of Analytical Techniques From The Extraction Of Bioactive Compounds From Kratom, Curry, Ginger, And Turmeric, Riley Bruno

Honors Program: Senior Projects (Public)

Plants, herbs, and spices have been used as medicines for thousands of years. Early civilizations often attributed healing properties of plants to magical or divine forces. However, as chemistry and analytical technology advanced between the 16th and 18th centuries, scientists began to understand that bioactive compounds within the plants actually caused these effects. Today, natural products remain extremely important in drug discovery. As the number of newly developed synthetic drugs declines, there has been renewed interest in identifying biologically active molecules from plants. Bioactive molecules are a group of diverse chemical compounds that stimulate a response in living tissues. The …

When Words Flow Like Water: How The Enbridge Line 3 Pipeline Environmental Impact Statement Failed To Prevent Hydrogeologic Harm In Minnesota, Carly Gutzmann

Journal of Earth and Life Science

For the aquifers of Minnesota, the environmental impact statement (EIS) was a promise of protection that never left the page. An environmental impact statement is meant to be an aid in the decision making process in order to ensure that projects consider potential environmental harms that may occur. However, they are often used instead as another regulatory box to check, rather than as active considerations when planning. As such, a project plan can be flawed from the start—if project developers only consider environmental impacts after they have already put considerable time, effort, and funding into their project as-is, they may …

A Hybrid Response Surface Methodology And Machine Learning Framework For Quantifying Effects Of Physicochemical Parameters On Pfas Distribution, Harsh V. Patel, Jazmin Green, Hyoshin Park, Stephanie Luster-Teasley Pass, Renzun Zhao

Engineering Management & Systems Engineering Faculty Publications

Predicting PFAS adsorption across diverse adsorbents and environmental matrices remains challenging because adsorbent physicochemical properties, PFAS molecular descriptors, and operational conditions simultaneously influence adsorption. This study develops and evaluates a unified hybrid modeling framework that integrates Response Surface Model (RSM) with machine-learning algorithms to quantify how six key variables, surface area, Log K_ow, pH_pzc, pK_a, log dose, and log-initial concentration, affect PFAS distribution coefficients (Log K_d). A data set of more than 1000 adsorption observations spanning 15 PFAS compounds, multiple adsorbent types, and a broad operational range was compiled and preprocessed using …

Rna-Sequence-Driven Identification Of Differentially Expressed Genes In Α-Crystallin-Deficient Zebrafish, Kehlie Hopper

SPARK Symposium Presentations

Fetal Alcohol Syndrome (FAS) is a condition that develops in infants when exposed to alcohol in utero, leading to physical impairments such as reduced eye size and disrupted retinal function. Alpha-crystallin A is a key structural protein required for proper lens development and maintenance of transparency, while Alpha-crystallin B plays a protective role against cellular stress during eye development. In this study, I compared AB wild-type (ABWT), αA-crystallin knockout (cryaa), and αB-crystallin knockout (cryaba) zebrafish to investigate how the loss of these proteins influences eye development under ethanol exposure. The cryaa mutants exhibited reduced eye size even under control conditions, …

Murder On The Menu, Andrea Florian, Leslie Deleon, Angela Simpkins, Anamika Chhetri

SPARK Symposium Presentations

You're invited to a birthday party in Maryland! There will be many guests and even...seafood cuisine at a fancy restaurant! All is well until one of our guests comes down with a peculiar sickness. Do you think you can figure out what happened?

Honeymoon Horror Story, Andrea Florian, Aunalise Terreri, Kiley St. John, Sienna White

SPARK Symposium Presentations

On what was supposed to be a romantic honeymoon getaway, a newly married couple’s paradise quickly turns dark. The wife, Julia Harper, is found dead under mysterious circumstances, and suspicion falls on her neuroscientist husband. As lies unravel, investigators discover that this honeymoon was never about love, but revenge. In the end, all that’s left is betrayal and secrets…Can you solve this murder mystery?

The Last Ball, Andrea Florian, Lili M. Wrenne, Mehrael Adly, Jia Howell

SPARK Symposium Presentations

Sixty-year old, billionaire, Walter Spencer has been found dead at his annual birthday celebration. Guests reported odd behavior before he passed with wild mood swings, speaking gibberish, and experiencing hallucinations. Close friends of Walter say his young 25-year-old wife was the last to see him. Are you able to solve his mystery?

A Sweet Deception, Andrea Florian, Ellis Stafford, Bridget Mcloud, Awi Siam

SPARK Symposium Presentations

Have you ever wanted to be a detective and solve a murder? Well, here is your chance! Bradley Thompson, an investment banker at JP Morgan, was murdered in his home, and we are relying on you to piece together the toxicological clues and find his killer! This murder-mystery activity will involve selecting different toxicological tests and evaluating evidence to determine who committed this heinous crime.

Data For Forthcoming Article: "Employing Zebrafish To Understand Genetic Drivers Of Epilepsy-Related Comorbid Behaviors", Colleen Carpenter-Swanson

Biology Faculty Data

Forthcoming from Frontiers in Pharmacology:

"Children with epilepsy frequently experience a range of significant comorbidities beyond seizures, such as motor dysfunction, cognitive impairment, and neurodevelopmental delays. In some cases, these comorbidities contribute more significantly to overall disease burden than the seizures themselves. To improve quality-of-life (QOL) for these children, treatment options should be selected that control seizures and ameliorate comorbidities. Unfortunately, such therapeutics remain largely elusive. Addressing this issue requires suitable preclinical models. Here we used CRISPR-generated zebrafish with single-gene mutations linked to pediatric epilepsy and applied clinically-relevant behavioral assays to study the effects of these mutations. Using high-throughput locomotion-based …

Murder Of The Magic Mushroom Man, Andrea Florian, Alexa Cabral, Olivia Fawkes, Emily Gomez

SPARK Symposium Presentations

Rowan Tucker is an heirloom vegetable farmer that lives in Newbury, VT on an 80-acre farm. Most of the money in Rowan’s name was from selling psilocybin mushrooms that he disguised as payments under “crop-selling”. He was found dead presenting symptoms early that morning of confusion, hallucinations, vomiting, sweating, and extreme salivation. How did he get murdered? Who did it?

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …

Neonicotinoid Bioaccumulation In Bluegill And Bullhead Within Lake Julia And Lake Zumwalde, Jake Stuber

Journal of Earth and Life Science

Brown Bullhead Ameiurus nebulosus, Yellow Bullhead Ameiurus natalis, and Bluegill Lepomis macrochirus are unique in their stark differences. Bullhead are scaleless bottom feeders that can tolerate high pollution and low O₂ conditions. In contrast, Bluegill are scaled, aggressive nesters and are less tolerant of high pollutants or low-oxygen conditions. Among these pollutants include a class of chemicals called neonicotinoids (hereafter referred to as neonics). Neonics are a class of insecticides primarily used within agriculture and pest management. Due to the effectiveness, application has escalated on a global scale. They have been well documented by many toxicology assessments. …

A Ubiquitous Organophosphate Flame Retardant Disrupts Energy And Glucose Homeostasis In Mice, Krystal M. Sewell, Kelly Oriakhi, Sara Y. Ngo Tenlep, Megan L. Weaver, Mansura Shahad Bawa, Se-Hyung Park, Shubh Saraswat, Xiaohua D. Zhang, Robert N. Helsley, Samir Softic, Cetewayo S. Rashid

Pharmacology and Nutritional Sciences Faculty Publications

Organophosphate flame retardants (OPFRs) are used in many consumer products, and their presence in our environment raises concerns about potential health dangers. In humans, exposure to OPFRs, such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is associated with metabolic disorders such as obesity, hyperglycemia, and insulin resistance. Our current study seeks to determine how TDCPP exposure affects body composition, glucose homeostasis, and energy balance in a rodent model. C57Bl/6 J mice were divided into two weight-matched groups and fed purified low phytoestrogen diets containing either 0.1 % DMSO (control) or TDCPP 415 mg/kg resulting in an approximate exposure of 50 mg/kg/day. Both male …

Contribution Of Metabolism-Independent Glucose Sensing To Metabolic Homeostasis, Nadia Rashid, Kavaljit H. Chhabra

Pharmacology and Nutritional Sciences Faculty Publications

Glucose sensing and signaling are central to cellular metabolic machinery for the regulation of metabolic homeostasis. Glucose sensing has been almost always assumed to be coupled with glucose metabolism; however, recent findings have unraveled metabolism-independent sensing mechanisms. Here, we discuss whether glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) may also function as glucose sensors independent of their roles in transporting glucose. Moreover, we review the emerging roles of G protein-coupled receptors (GPCRs) in sensing glucose and, consequently, initiating its signaling pathways in a cell-specific manner. Altogether, this review offers insights into the newly identified glucose sensing mechanisms and highlights the …