Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …

The Increase Of Fentanyl Use In Young Adults And Its Relationship To Mental Illness, Madison Lilleberg, Madison Regel, Bashaer Abdushakour, Rosalee Allan

2022 Symposium

The abuse of prescription pain medication has risen to exponential levels in the United States within the past few years, leading to overdose deaths. The opioid epidemic sparked the popularity of the use of Fentanyl due to its highly potent pain-fighting properties. What was once approved to manage pain symptoms for cancer patients is now being used by thousands of young individuals irresponsibly and poses a threat to the health of our population. It is also becoming increasingly common worldwide to find this synthetic opioid mixed with other illicit drugs.

The scope of the research focuses on studies on self-medication …

Discovering The Role Of Repeat Sequences In Regulation Of The Phaz Gene In Streptomyces Sp. Sfb5a, Harrison Senter, Stephen Baron

Honors Projects

Streptomyces sp. SFB5A is an actinomycete (filamentous bacterium) that degrades PHB using an extracellular PHB depolymerase. PHB depolymerase synthesis is induced by growth on PHB and repressed by glucose (or other preferred carbon sources)², which suggests that there is transcriptional regulation of its corresponding gene, phaZ. Binding sites are suspected to be the repeat sequences found in the phaZ gene. There are 3 different sets of primers that can be made in order to emphasize specific functional repeats while disrupting the functionality of others. The goal of the project is to transform Streptomyces sp. 5A with constructs …

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSB and SJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSB and SJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has killed an …

Jnk And Nf-Κb Cell Signaling Pathways In Cardiovascular Disease Present Potential Targets For Curcumin Therapy, Mary Richfield

Senior Honors Theses

Curcumin (diferuloylmethane) is a compound derived from the rhizomes of Curcumin longa that has been long used for medicinal purposes. Curcumin alleviates the pathology of cardiovascular diseases, including atherosclerosis, aneurysm, and cardiomyopathy. The mechanism of curcumin therapy is under active research. The NF-κB and JNK pathways are two that curcumin interacts with to block inflammatory processes, apoptosis, and fibrotic tissue remodeling to prevent the pathologies of cardiovascular disease. While curcumin has demonstrated powerful mediation of cardiovascular disease, its bioavailability in body tissues is limited due to the instability and hydrophobicity of its structure. Further work is underway to stabilize …

Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke

Senior Honors Theses

The results of a folate deficiency study affecting cognition in mice suggested the altered genes may be controlled by a transcription factor known as Zinc Finger Protein 410 (Zfp410). Due to a lack of literature on Zfp410’s interacting proteins and DNA-binding location, our study aims to further elucidate the role Zfp410 plays in affecting cognition. A custom antibody was used to determine the Zfp410 isoforms present in mouse and rat brains. Moreover, the antibody was used to determine the binding partners of Zfp410 in the brain and locate specific genomic regions/sequences with which it associates in vivo. These results may …

Promoting Sustainable Responses To The Us Opioid Epidemic With Community-Academic Partnerships: Qualitative Outcomes From A Statewide Program, David L. Driscoll, Alison Evans Cuellar, Vinod Agarwal, Debra Jones, Kathy Hosig, Mary Beth Dunkenberger

Economics Faculty Publications

Background: Drug overdose deaths in the United States have continued to increase at an alarming rate. The United States is facing two devastating public health crises– the opioid epidemic and the COVID-19 pandemic. Within this context, one of the most ambitious implementation studies in addiction research is moving forward. Launched in May 2019, the HEALing Communities Study (HCS) was developed by the National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) as part of the Helping to End Addiction Long-termSM Initiative (National Institutes of Health, 2020). The goal for this research was to reduce …

Microplastics, The Environment, And Reproductive Health: How Is The Accumulation Of Microplastics In Our Environment And Bodies Impacting Reproductive Health?, Katherine Hayward

Independent Study Project (ISP) Collection

As global trends in both production and consumption of plastics continue to evolve, the bioaccumulation and biomagnification of microplastic particles in our everyday lives follow suit. This increasingly relevant problem has only recently been explored in the context of global health, and more specifically, reproductive health. Along with this steady increase in plastics and our exposure to them, researchers have separately observed adverse patterns in reproductive health. The chemicals involved throughout the microplastic life cycle may be playing a key role in these simultaneous patterns. With the aid of previous studies and publications on microplastics, exposure pathways, endocrine disruptors, and …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 2 – Categorical Bivariate Analysis And Attributable Fractions, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: As the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco. Methods: SEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) from National Cancer Institute in US states 2001–2017. Drug exposures taken from the National Survey of Drug Use and Health 2003–2017, response rate 74.1%. Federal seizure data provided …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 3 – Spatiotemporal, Multivariable And Causal Inferential Pathfinding And Exploratory Analyses Of Prostate And Ovarian Cancers, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: The epidemiology of cannabinoid-related cancerogenesis has not been studied with cutting edge epidemiological techniques. Building on earlier bivariate papers in this series we aimed to conduct pathfinding studies to address this gap in two tumours of the reproductive tract, prostate and ovarian cancer. Methods: Age-standardized cancer incidence data for 28 tumour types (including “All (non-skin) Cancer”) was sourced from Centres for Disease Control and National Cancer Institute using SEER*Stat software across US states 2001–2017. Drug exposure was sourced from the nationally representative household survey National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 1 - Continuous Bivariate Analysis, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background

The genotoxic and cancerogenic impacts of population-wide cannabinoid exposure remains an open but highly salient question. The present report examines these issues from a continuous bivariate perspective with subsequent reports continuing categorical and detailed analyses.

Methods

Age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) was sourced using SEER*Stat software from Centres for Disease Control and National Cancer Institute across US states 2001–2017. It was joined with drug exposure data from the nationally representative National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental Health Services Administration 2003–2017, response rate 74.1%. …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Agents, David Salehi, Saghar Mozaffari, Khalid Zoghebi, Sandeep Lohan, Dindyal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of cyclic peptides, [(DipR)(WR)₄], [(DipR)₂(WR)₃], [(DipR)₃(WR)₂], [(DipR)₄(WR)], and [DipR]₅, and their linear counterparts containing arginine (R) as positively charged residues and tryptophan (W) or diphenylalanine (Dip) as hydrophobic residues, were synthesized and evaluated for their molecular transporter efficiency. The in vitro cytotoxicity of the synthesized peptides was determined in human epithelial ovary adenocarcinoma cells (SK-OV-3), human lymphoblast peripheral blood cells (CCRF-CEM), human embryonic epithelial kidney healthy cells (HEK-293), human epithelial mammary gland adenocarcinoma cells (MDA-MB-468), pig epithelial kidney normal cells (LLC-PK1), and human epithelial …

Succinic Semialdehyde Dehydrogenase Deficiency (Ssadhd): Qualitative Needs Assessment For Patients With A Rare Neurological Disorder, Cassandra Bovee, Kayla Woodring

Annual Research Symposium

No abstract provided.

A Quantitative Analysis Of The Efficacy Of Various Essential Oils Against The Sars Cov-2 Virus, Elizabeth Wagstaff, Chandrelyn Kraczek, Jack Brandon Lopez

Annual Research Symposium

A poster presentation and abstract for the Roseman Symposium. The project focuses on testing 3 essential oil blends and two disinfectants containing an essential oil blend against SARS CoV-2 in response to the COVID-19 pandemic. The project procedure involves plaque assays, disinfection, and neutralization techniques.

Dissecting Mutational Allosteric Effects In Alkaline Phosphatases Associated With Different Hypophosphatasia Phenotypes: An Integrative Computational Investigation, Fei Xiao, Ziyun Zhou, Xingyu Song, Mi Gan, Jie Long, Gennady M. Verkhivker, Guang Hu

Mathematics, Physics, and Computer Science Faculty Articles and Research

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone mineralization and is highly variable in its clinical phenotype. The disease occurs due to various loss-of-function mutations in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). In this work, a data-driven and biophysics-based approach is proposed for the large-scale analysis of ALPL mutations-from nonpathogenic to severe HPPs. By using a pipeline of synergistic approaches including sequence-structure analysis, network modeling, elastic network models and atomistic simulations, we characterized allosteric signatures and effects of the ALPL mutations on protein dynamics and function. Statistical analysis of molecular features computed for the …

Antibacterial Activity, Structure-Activity Relationships, And Scale-Up Reaction Of 1,3,4-Oxadiazoles, Olivia Marie Smith

Undergraduate Honors Thesis Projects

Oxadiazoles are compounds in the field of organic chemistry that have been gathering interest in the medicinal chemistry and microbiology communities for their biological properties, which range from anti-inflammatory agents, to chemotherapy drugs, to antibiotics. The synthesis of oxadiazoles can be difficult due to the expensive and complex nature of the techniques used as well as the volatile reagents and elevated temperatures that are often required in organic synthesis. The Grote lab has recently developed a new method for the synthesis of 1,3,4-oxadiazoles under mild conditions. The goals of this thesis were thus twofold: to develop a viable scale-up procedure …

Combination Of Amphiphilic Cyclic Peptide [R4W4] And Levofloxacin Against Multidrug-Resistant Bacteria, Muhammad Imran Sajid, Sandeep Lohan, Shun Kato, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Bacterial resistance is a growing global concern necessitating the discovery and development of antibiotics effective against the drug-resistant bacterial strain. Previously, we reported a cyclic antimicrobial peptide [R₄W₄] containing arginine (R) and tryptophan (W) with a MIC of 2.67 µg/mL (1.95 µM) against methicillin-resistant Staphylococcus aureus (MRSA). Herein, we investigated the cyclic peptides [R₄W₄] or linear (R₄W₄) and their conjugates (covalent or noncovalent) with levofloxacin (Levo) with the intent to improve their potency to target drug-resistant bacteria. The physical mixture of the Levo with the cyclic [R_{4 …}

Emerging Drug Targets And New Drugs In The Treatment Of Psoriatic Arthritis, Carmen Lariccia, Natalie Lennartz, Jessica Lewe, Jeffery Allison

Pharmacy and Wellness Review

Psoriasis is an autoimmune disease characterized by painful skin lesions. When joints and connective tissue also become involved, the condition is referred to as psoriatic arthritis (PsA). Current treatments for moderate to severe PsA include therapies used to treat rheumatoid arthritis (RA) despite differences in disease presentation which includes factors such as peripheral disease, sacroiliitis, stiffness, presence of rheumatoid factor and psoriasis. Treatment out-comes for PsA are measured by the American College of Rheumatology (ACR) Responder Index (ACR20) and the Dis-ease Activity Score for 28 joints (DAS28). First-line treatment includes disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine or leflunomide …

Management Of Hyperkalemia To Prevent Cardiac Arrest, Jennifer Harklerode, Amber Paul, Crystal Zheng, Olivia Vanscoy, Olivia Henton, Mark Olah

Pharmacy and Wellness Review

Hyperkalemia is a metabolic problem that may be life threatening if left untreated. Cardiac arrhythmias may develop with the potential to lead to cardiac arrest and death. Hyperkalemia can oftentimes be undiagnosed due to the lack of clear, specific symptoms and inconclusive variations in electrocardiogram (ECG) readings and lab values. Therefore, it is important to recognize risk factors that can potentially in-crease serum potassium levels. Screening for medications that increase serum potassium levels and educating patients are steps that both inpatient and outpatient health care professionals can take to increase early detection and prevention of a hyperkalemic episode. It is …