Amino Acids, Peptides, and Proteins Commons^™

Impaired Dnajb2 Response To Heat Shock In Fibroblasts From A Neuropathy Patient With Dnajb2/Hsj1 Mutation: Cystamine As A Potential Therapeutic Intervention, Raj K. Pradhan, Nikolas G. Kinney, Brigid K. Jensen, Hristelina Ilieva

Farber Institute for Neuroscience Faculty Papers

Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an adult patient with severe sensory–motor polyneuropathy. This mutation is predicted to affect both isoforms of the protein. DNAJB2 (HSP40), a key member of the heat shock protein family, plays a critical role in cellular protection and stress, including response to heat shock. DNAJB2 traffics unfolded proteins to another heat shock protein, HSP70, and activates its ATPase …

Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria Tran, Shira N Johnston, Maria Tsingas, Ruteja Barve, Ramkrishna Mitra, Richard Loeser, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (Acan^CreERT2; Sirt6^fl/fl). Histological studies showed a degenerative phenotype in knockout mice …

Rationally Designed Pentapeptide Analogs Of Aβ19-23 Fragment As Potent Inhibitors Of Aβ42 Aggregation, Sachin B. Baravkar, Yan Lu, Qi Zhao, Hongying Peng, Weilie Zhou, Song Hong

School of Medicine Faculty Publications

Amyloid beta (Aβ42 and Aβ40) aggregation, along with neurofibrillary tangles, is one of the major neurotoxic events responsible for the onset of Alzheimer's disease. Many potent peptide-based inhibitors mainly focusing on central hydrophobic core Aβ16-20 (KLVFF) have been reported in recent years. Herein, we report pentapeptides -, based on the β-turn-inducing fragment Aβ19-23 (FFAED). The synthesis of peptides - was carried out using Fmoc/tBu-based solid-phase peptide synthesis technique, and it was found that pentapeptide potently inhibit the aggregation propensity of Aβ42, when incubated with it at 37 °C for 48 h. The aggregation inhibition study was conducted using thioflavin T-based …

Rescue Of The First Mitochondrial Membrane Carrier, The Mpic, By Tat-Mediated Protein Replacement Treatment, Samar Zabit, Orly Melloul, Michal Lichtenstein, Erin L. Seifert, Haya Lorberboum-Galski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mitochondrial phosphate carrier (mPiC), encoded by the nuclear gene SLC25A3, is synthesized with an N-terminus mitochondrial targeting sequence (MTS), enabling its import into the mitochondria. mPiC imports inorganic phosphate (P_i) into the mitochondrial matrix for ATP production and other matrix phosphorylation reactions, as well as regulates mitochondrial Ca²⁺ uptake and buffering of matrix Ca²⁺. PiC also imports copper (Cu), crucial to COX subunit holoenzyme assembly. Variants in SLC25A3 exist and lead to mPiC deficiency (MPCD), cause a rare autosomal recessive disease with no current cure; patients with MPCD usually die within the first …

Scoping Literature Review: The Role Of Leptin In Autism Spectrum Disorder (Asd) And Associated Obesity, Diana B. Riestra, Andrea Iannuzzelli

Rowan-Virtua Research Day

Overweight and obesity (OW/OB) are significant concerns among individuals with Autism Spectrum Disorder (ASD), yet the underlying causes remain unclear. Emerging evidence points to metabolic and hormonal factors—particularly leptin, a hormone involved in appetite regulation—as potential contributors. This scoping review examined five key studies from 2003 to 2024 that investigated the relationship between leptin and ASD in overweight populations. Across studies, individuals with ASD consistently exhibited elevated leptin levels compared to controls. While some findings also noted changes in other adipokines, such as lower resistin or progranulin, leptin was the most consistently dysregulated. These patterns suggest systemic alterations in energy …

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Caveolin-1: An Ambiguous Entity In Breast Cancer, Naveen Chintalaramulu, Dhirendra Pratap Singh, Biplov Sapkota, Dayanidhi Raman, Suresh Alahari, Joseph Francis

School of Medicine Faculty Publications

Breast cancer (BC) is the most frequently diagnosed cancer in women and the second leading cause of death from cancer among women. Metastasis is the major cause of BC-associated mortality. Accumulating evidence implicates Caveolin-1 (Cav-1), a structural protein of plasma membrane caveolae, in BC metastasis. Cav-1 exhibits a dual role, as both a tumor suppressor and promoter depending on the cellular context and BC subtype. This review highlights the role of Cav-1 in modulating glycolytic metabolism, tumor-stromal interactions, apoptosis, and senescence. Additionally, stromal Cav-1's expression is identified as a potential prognostic marker, offering insights into its contrasting roles in tumor …

Ocular Surface Glycocalyx In Health And Disease, Rafael Martínez-Carrasco, Ajay Sharma

Pharmacy Faculty Articles and Research

The glycocalyx is a dynamic carbohydrate-enriched structure that forms a dense coating on the surface of animal cells, including those at the ocular surface. It plays a critical role in maintaining cellular functions and it has a significant influence in disease processes. At the ocular surface, glycoproteins such as mucins are essential for hydration, lubrication, and barrier protection. Proteoglycans and glycolipids contribute to cell signaling, and mediate interactions with pathogens. Alterations in the glycocalyx are implicated in a spectrum of ocular conditions, including dry eye disease, ocular allergies, infections, and systemic diseases such as Graft-versus-host disease (GVHD) and diabetes mellitus. …

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

Refractory Dermatitis Evolving Into Lupus Spectrum Disease In The Setting Of Dupilumab Use, Jonathan M. Joseph, Jacob Kilgore, Nicholas Culotta

School of Medicine Faculty Publications

Cutaneous lupus erythematosus (CLE) encompasses a broad range of clinical and histopathologic variants that can overlap with other dermatologic entities, complicating accurate diagnosis. We report the case of a 42-year-old male patient who initially presented with a diffuse pruritic eruption presumed to be atopic dermatitis, for which dupilumab was initiated. Within the following weeks, the patient developed a fever of unknown origin and diarrhea, raising concern for an atypical drug-related reaction or an unmasked autoimmune process. Subsequent biopsies demonstrated evolving histopathologic features, including superficial and deep perivascular dermatitis suggestive of drug eruption. In addition, a dermal mucin deposition with mixed …

Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning of SARS-CoV-2 spike residues, and binding free energy computations for two distinct groups …

Il-1Β In Neoplastic Disease And The Role Of Its Tumor-Derived Form In The Progression And Treatment Of Metastatic Prostate Cancer, Yetunde Oyende, Luke Taus, Alessandro Fatatis

Kimmel Cancer Center Faculty Papers

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β …

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

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 …

Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …

Ribosome Hibernation In Mycobacterium Abscessus And Its Effect On Antibiotic Resistance, Ryan Treen

Electronic Theses & Dissertations (2024 - present)

Non-tuberculosis mycobacteria (NTM) represent a diverse repertoire of species, most of which are ubiquitous in the environment. Some NTM species, such as Mycobacterium abscessus, can cause life-threatening infections in people with underlying medical conditions. The clinical incidence of such infections is on the rise, posing an emerging threat to public health. M. abscessus is characterized by intrinsic and acquired antibiotic resistance, complicating treatment strategies. Most chemotherapeutic approaches for M. abscessus infection target the bacterial ribosome, necessitating a better understanding of the physiological processes which confer this resistance. Multiple mycobacterial species respond to zinc-limiting conditions by inducing remodeling and hibernation …

Combination Of Hsp90 Inhibitors And Hsp70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis In Rabbits, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Dan E. Austin Jr., Len E. Murray, John D. Catravas

Bioelectrics Publications

Combined therapies with Heat Shock Protein 90 (HSP90) inhibitors and Heat Shock Protein 70 (HSP70) inducers are gaining significant interest in cancer and cardiovascular research. Here, we tested the hypothesis that HSP90 inhibitors and HSP70 inducers, together, can block the development of pulmonary fibrosis. We exposed New Zealand White Rabbits to hydrochloric acid (HCl, 0.1 N, 1.5 mL/kg), one of the top five chemicals most commonly involved in accidental exposures and inhalation injuries worldwide, and treated animals with either the orally available HSP90 inhibitor TAS-116 (1.7 mg/kg 5x/week) or TAS-116 combined with the HSP70 inducer, geranylgeranyl acetone (GGA, 50 mg/kg, …

Asymmetric Synthesis Of The Hiv Protease Inhibitor Tmc-126 And An Anti-Malarial Agent Via A Titanium Tetrachloride Mediated Asymmetric Glycolate Aldol Addition Reaction. Redefining The Curtius Rearrangement Reaction Via Dehomologation Of Carboxylic Acids Bearing Alpha-Leaving Groups, Kweku Amaning Affram

Theses and Dissertations

Acquired Immune Deficiency Syndrome (AIDS) and malaria are two devastating infectious diseases caused by HIV and Plasmodium parasites. AIDS is caused by HIV-1 and HIV-2, transmitted through sexual contact, blood transfusions, needle sharing, and perinatal routes. Malaria, caused by plasmodium parasites through mosquito bites. Today, millions of people around the world have been infected with HIV and malaria and much research has been done to treat it. However, despite advancements in therapeutic options, these diseases remain a significant global health threat, particularly in developing countries due to the emergence of drug-resistant strains for both HIV and malaria complicating eradication efforts. …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

An E. Coli Two-Hybrid System To Investigate Human Protein-Protein Interactions, Rebecca M. Richardson, Sarah M. Ho, Lane Tong, Morgan G. Daniels, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Abstract

The LexA-E. coli two-hybrid (LexA-E2H) system was initially developed to study interactions between microbial proteins in an Escherichia coli (E. coli) environment. We here demonstrate its utility for studying mammalian protein interactions. Specifically, this study uses LexA-E2H to provide the first direct and quantitative validation of Glucose Regulated Protein 78 (GRP78) binding to the cleaved-Prostate Apoptosis Response 4 (cl-Par-4) tumor suppressor. Furthermore, the results establish that this interaction does not require phosphorylation of either protein. MacConkey agar was used for initial detection of the interaction through colorimetric colony screening, distinguishing pale white-pink colonies (+ interaction) from …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Proteoglycan 4 (Lubricin) And Regulation Of Xanthine Oxidase In Synovial Macrophage As A Mechanism Of Controlling Synovitis, Khaled A. Elsaid, Ling X. Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Tannin A. Schmidt, Gregory D. Jay

Pharmacy Faculty Articles and Research

Background

Synovial macrophages (SMs) are important effectors of joint health and disease. A novel Cx3CR1 + TREM2 + SM population expressing the tight junction protein claudin-5, was recently discovered in synovial lining. Ablation of these SMs was associated with onset of arthritis. Proteoglycan 4 (PRG4) is a mucinous glycoprotein that fulfills lubricating and homeostatic roles in the joint. The aim of this work is to study the role of PRG4 in modulating synovitis in the context of SM homeostasis and assess the contribution of xanthine oxidase (XO)-hypoxia inducible factor alpha (HIF-1a) axis to this regulation.

Methods

We used Prg4FrtloxP/FrtloxP …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Induction Of Tier 2 Hiv-Neutralizing Iga Antibodies In Rhesus Macaques Vaccinated With Bg505.664 Sosip, Justin C. Smith, Prabhu S. Arunachalam, Traci H. Legere, Lisa A. Cavacini, Eric Hunter, Bali Pulendran, Rama R. Amara, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

BACKGROUND: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified. METHODS: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.664 SOSIP and 3M-052 adjuvant, which is …

Evolving Treatment Strategies For Systemic Lupus Erythematosus In Clinical Practice: A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Chandni R. Patel, Alison M. Hawkins, Caroline R. Burroughs, Kristin Nicole Bembenick, Chizoba N. Mosieri, Shahab Ahmadzadeh, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Dentistry Faculty Publications

Systemic lupus erythematosus (SLE) is an autoimmune disease that more commonly affects African American people, although it is seen in people of all racial backgrounds. This condition is characterized by a dysregulated immune response resulting in widespread inflammation. Clinical manifestations caused by this inflammation include arthritis, anemia, cutaneous rashes, pleuritis, and nephritis. Treatment for SLE aims to reduce disease activity and maintain a state of low inflammation. In this regard, numerous treatments are used, such as hydroxychloroquine, glucocorticoids, and non-glucocorticoid immunosuppressants such as methotrexate. Related to these drugs resulting in significant adverse effects and being ineffective in controlling SLE symptoms …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …