Enzymes and Coenzymes Commons^™

Optimizing Itpa R178c Assays Via Hplc, Jared J. Reisnouer, Wally D. Pines

2026 Symposium

Two of the major nucleotide bases in DNA and RNA (Adenine and Guanine) are derived from the purine Inosine Monophosphate (IMP). IMP may occasionally form the noncanonical nucleotide Inosine Triphosphate (ITP) within the cell and become incorporated into DNA during replication, leading to potentially lethal errors. To combat this, human cells produce the “housekeeping” enzyme Inosine Triphosphatase (ITPA) to revert ITP to IMP. A mutation of this protein that replaces the 178th amino acid Arginine with Cysteine (R178C) is associated with a fatal infantile encephalopathy. Previous assessments of enzyme-substrate binding and catalysis for ITPA variants have been run at a …

Genomic Ascertainment Of Chek2 -Related Cancer Predisposition, Sunyoung Kim, Jung Kim, Mark Ramos, Jeremy Haley, Diane Smelser, H. Shanker Rao, Uyenlinh L. Mirshahi, Katherine L. Nathanson, Barry I. Graubard, Hormuzd A. Katki, David Carey, Douglas R. Stewart

School of Graduate Studies Faculty Publications

Importance: There is clear evidence that deleterious germline variants in CHEK2 increase risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Objective: To quantify the prevalence of as well as cancer risk and survival associated with CHEK2 germline pathogenic and likely pathogenic variants using genomic ascertainment. Design, Setting, and Participants: This case-control study used 2 electronic health record-linked and exome-sequenced biobanks: UK Biobank (n = 469765) and Geisinger MyCode (adults only; n = 167050). Variants were classified according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Cases …

Bromelain-Based Enzymatic Debridement Of A Third-Degree Burn To Skin-Grafted Bowel, Shengqing Wang, Janie Faris, Kareem Abdelfattah, Samuel Mandell, M Victoria Miles

School of Medicine Faculty Publications

Burn injuries over previously grafted tissue present a formidable challenge for excision and debridement, particularly when there are critical underlying structures such as bowel. Enzymatic debridement with the recently approved anacaulase-bcdb, a bromelain-based enzymatic debridement gel (Nexobrid), presents an additional method of burn excision that may be useful in such a situation. This brief report presents the management of a complex third-degree burn over a remotely skin-grafted bowel mass using anacaulase-bcdb gel. This report is written with documented patient consent and approval by the Human Research Protection Program office in compliance with institutional policy. A 52-year-old man presented to our …

Determining Risk Factors And Rate Of Surgery After Collagenase Injections For Dupuytren Contracture, Ryan C. Cha, Juliet S. Chung, Sina Ramtin, Asif M. Ilyas

Department of Orthopaedic Surgery Faculty Papers

Purpose: Collagenase injections are a nonsurgical treatment for Dupuytren contracture, but their long-term effectiveness in preventing surgery remains unclear. This study aimed to evaluate the rate of surgical intervention following collagenase treatment and identify whether specific risk factors increase the likelihood of future surgical correction. Methods: This retrospective cohort study utilized the TriNetX US Collaborative network to identify patients diagnosed with Dupuytren contracture between January 2007 and September 2024. Patients initially treated with collagenase injections were identified using relevant current procedural terminology codes. Procedure-specific current procedural terminology codes were then used to determine which patients underwent a subsequent fasciectomy or …

Advances In Molecular Imaging Of Vegfrs: Innovations In Imaging And Therapeutics, Hanieh Karimi, Sarah Lee, Wenqi Xu, Sigrid A. Langhans, David K. Johnson, Erik Stauff, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like 64Cu-bevacizumab and 89Zr-ramucirumab, has emerged as a powerful …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

Investigating The Production Challenges Of The P100.1 Phage Endolysin, Jonah O. Frago

EWU Masters Thesis Collection

Acne vulgaris is one of the most common skin diseases globally. One key aspect of acne pathogenesis is the disturbance of healthy strain diversity of the skin bacterium Cutibacterium acnes. Many acne treatments are antimicrobial; however, these treatments are generally nonspecific and carry a variety of side effects in addition to contributing to rising antibiotic resistance. Lytic bacteriophages (or phages) are viruses that infect and kill bacteria. Their lytic lifestyle is facilitated by enzymes called endolysins. Phages have been studied as an alternative to traditional antimicrobials in acne treatment and have shown reduced C. acnes load in acne lesions and …

5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker

Departmental Honors & Graduate Capstone Projects

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed …

Cd8Α Structural Domains Enhance Gucy2c Car-T Cell Efficacy, Trevor R. Baybutt, Ariana A. Entezari, Adi Caspi, Ross E. Staudt, Robert D. Carlson, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite success in treating some hematological malignancies, CAR-T cells have not yet produced similar outcomes in solid tumors due, in part, to the tumor microenvironment, poor persistence, and a paucity of suitable target antigens. Importantly, the impact of the CAR components on these challenges remains focused on the intracellular signaling and antigen-binding domains. In contrast, the flexible hinge and transmembrane domains have been commoditized and are the least studied components of the CAR. Here, we compared the hinge and transmembrane domains derived from either the CD8ɑ or CD28 molecule in identical GUCY2C-targeted third-generation designs for colorectal cancer. While these structural …

Janus Kinase (Jak) Inhibitors: A New Frontier In The Treatment Of Vitiligo, Catherine F. Alapatt, Amanda Greenspan, Mohammad Fardos

Rowan-Virtua Research Day

Up to 70 million people worldwide suffer from vitiligo, an autoimmune disease characterized by the destruction of melanin. Current treatment options vary in efficacy. The disease manifests clinically as white circular macules of depigmentation seen primarily on the face and appendages.1 The pathophysiology of vitiligo is multifactorial and still being studied. One proposed mechanism behind the pathophysiology of vitiligo involves the upregulation of interferon gamma (IFN-γ) with downstream effects on JAK/STAT pathways resulting in CXCL10 transcription.1,2 Here we discuss Ruxolitinib, a topical JAK inhibitor, that recently passed its clinical trial phase, and Ritlecitinib, an oral JAK inhibitor which is currently …

Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia

Pharmacy Faculty Articles and Research

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Identification And Characterization Of Butyrate-Producing Species In The Human Gut Microbiome, Grace Maline

Theses/Capstones/Creative Projects

Inflammatory Bowel Diseases (IBD) including ulcerative colitis, indeterminate colitis, and Crohn’s disease are increasingly common conditions that places a high physical and financial burden on individuals and global healthcare systems. Though many treatments exist for these conditions, their unpredictable nature and causation make them difficult to manage across the variety of IBD patients. Additionally, many of these treatments come with undesirable side effects or modes of delivery. Therefore, it is worthwhile to explore the use of Short Chain Fatty Acids (SCFAs) such as butyrate whose affects in the human gut include decreased inflammation and decreased risk of colorectal cancer. As …

Carbon Dots As Artificial Peroxidases For Analytical Applications, Shih-Chun Wei, Yang-Wei Lin, Huan-Tsung Chang

Journal of Food and Drug Analysis

Nanozymes have become attractive in analytical and biomedical fields, mainly because of their low cost, long shelf life, and less environmental sensitivity. Particularly, nanozymes formed from nanomaterials having high surface area and rich active sites are interesting since their activities can be tuned through carefully controlling their size, morphology, and surface properties. This review article focuses on preparation of carbon dots (C dots) possessing peroxidase-like activity and their analytical applications. We highlight the important roles of the oxidation states and surface residues of C dots and their nanocomposites with metal, metal oxides, or metal sulfides playing on determining their specificity …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Urolithin A, A Gut Metabolite, Improves Insulin Sensitivity Through Augmentation Of Mitochondrial Function And Biogenesis, Ashley Mulcahy Toney, Rong Fan, Yibo Xian, Virginia Chaidez, Amanda E. Ramer-Tait, Soonkyu Chung

Department of Nutrition and Health Sciences: Faculty Publications

Objective: Urolithin A (UroA) is a major metabolite of ellagic acid produced following microbial catabolism in the gut. Emerging evidence has suggested that UroA modulates energy metabolism in various cells. However, UroA’s physiological functions related to obesity and insulin resistance remain unclear. Methods: Male mice were intraperitoneally administrated either UroA or dimethyl sulfoxide (vehicle) along with a high-fat diet for 12 weeks. Insulin sensitivity was evaluated via glucose and insulin tolerance tests and acute insulin signaling. The effects of UroA on hepatic triglyceride accumulation, adipocyte size, mitochondrial DNA content, and proinflammatory gene expressions were determined. The impact of UroA on …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

An Automated Syringe Pump System For Improving The Reproducibility Of Dynamic Hyperpolarized Mri Phantoms, Harlee G. Harrison

Dissertations and Theses (Open Access)

AN AUTOMATED SYRINGE PUMP SYSTEM FOR IMPROVING THE REPRODUCIBILITY OF DYNAMIC HYPERPOLARIZED MRI PHANTOMS

Harlee Grace Harrison, B.S.

Advisory Professor: James Bankson, Ph.D.

Magnetic Resonance Imaging (MRI) is a powerful tool in the diagnosis of cancer due to its ability to provide good soft tissue contrast and image resolution without the use of ionizing radiation. The use of hyperpolarized pyruvate as a contrast agent for tumor metabolism during MR scans has the potential to provide information about tumor metabolism in vivo that is not available from traditional imaging measurements or any other method. Hyperpolarization is achieved through dynamic nuclear polarization. …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Drug Interactions With Glutaredoxin Orthologues, Kahlilah R. Napper, Thomas C. Leeper, Ram Khattri, Daniel Morris, Caroline Davis

Williams Honors College, Honors Research Projects

Glutaredoxin, an enzymatic protein, is an important component of cell viability and function. It catalyzes reactions involved in DNA synthesis and innate immunity [1,4]. Glutaredoxin is also essential in antibiotic resistance in pathogenic bacterial species. Pseudomonas aeruginosa in particular is responsible for infecting the lung tissue of its human hosts, resulting in the development of pneumonia and cystic fibrosis [3]. Because glutaredoxin is pertinent in cell proliferation of eukaryotic and bacterial cells alike, medicinal fragments that take advantage of the subtle differences in protein structure of the orthologous proteins can be synthesized and enhanced to bind bacterial glutaredoxins, without inhibiting …

The Effect Of Maté On Enzymes Involved In The Recovery From Oxidative Stress, Amina Sadik, Theodore Chang

College of Osteopathic Medicine (TUN) Publications and Research

In comparing the effect of Maté to that of green tea, it has been shown that Maté has higher anti-oxidative properties. We have shown that the extract of Yerba Maté, paraguariensis, leaves does indeed have strong anti-oxidative properties through the evaluation of its scavenging activity and its ability of assist cardiomyocytes in their recovery from induced oxidative stress using both spectroscopy, a colorimetric assay and flow cytometry. In order to elucidate the mechanism behind this action, we quantified the enzymes known to be expressed naturally by cells under oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase. These enzymes …

Characteristics Of The Recovery Of The Coenzyme A-Synthesizing Protein Complex From Saccharomyces Cerevisiae, Stanley Joseph Tarnowski Jr.

Theses and Dissertations (ETD)

A multienzyme complex contained in Bakers' yeast (Saccharomyces cerevisiae) which synthesizes CoA has been named the coenzyme A-synthesizing protein complex (CoA-SPC). The CoA-SPC has been shown to be insoluble in the crude Bakers' yeast cell lysate formed by exposing the yeast cell to ether and dry ice. Only after solubilization has this multienzyme complex been shown to catalyze the formation of bound dephospho-CoA utilizing the substrates adenosine triphosphate, D-pantothenic acid and L-cysteine. A low molecular weight component or components of the soluble fraction of the yeast cell and chloride ion appears to be responsible for the solubilization of CoA-SPC. This …

The Purification, Properties And Subunit Structure Of Glycerol Dehydrogenase, Michael James Barrett

Theses and Dissertations (ETD)

The inducible, NAD-linked glycerol dehydrogenase (E.C. 1.1.1.6) of a guanine requiring mutant of A. aerogenes has been purified to homogeneity. The molecular weight of the pure enzyme was found to be 3.4 x 10⁵ daltons. The sedimentation coefficient of the enzyme was 10.7 x 10^-13 sec.^-1. The diffusion constant was 3.07 x 10^-7 cm²/sec.

The partial specific volume calculated from the amino acid composition was 0.72 ml/g. The following kinetic parameters were determined; K_m glycerol, 2.4 x 10^-3 m, K_m NAD, 2.8 x 10^-4 M, K_m dihydroxyacetone, 5.1 …