Biochemistry, Biophysics, and Structural Biology Commons^™

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Hedgehog Signaling And Congenital Disorders; The Case Of Anencephaly And Polydactyly, Joshua Towery

First-Year Research Immersion (FRI) Scholarship

The Hedgehog pathway is a fundamental signaling pathway in the human body; involved in carcinogenesis, stem cell maintenance, as well as limb patterning in embryonic development. Originally discovered in drosophila, their initial discovery, and subsequent analysis revealed many novel pieces of information about the mechanisms inside the human body, as many core components of the signaling pathway are carried over from fruit flies to humans. Because of the key roles hedgehog signaling plays in human development, dysfunction and mutations in the pathway can be detrimental. This review will focus on two congenital birth defects thought to be caused by hedgehog …

Neurotensin Modulates Ovarian Vascular Permeability Via Adherens Junctions, Andrew Pearson, Ketan Shrestha, Thomas E. Curry, Diane M. Duffy

UK CARES Faculty Publications

Neurotensin (NTS) is a 13-amino acid peptide which is highly expressed in the mammalian ovary in response to the luteinizing hormone surge. Antibody neutralization of NTS in the ovulatory follicle of the cynomolgus macaque impairs ovulation and induces follicular vascular dysregulation, with excessive pooling of red blood cells in the follicle antrum. We hypothesize that NTS is an essential intrafollicular regulator of vascular permeability. In the present study, follicle injection of the NTS receptor antagonist SR142948 also resulted in vascular dysregulation. To measure vascular permeability changes in vitro, primary macaque ovarian microvascular endothelial cells (mOMECs) were enriched from follicle aspirates …

A Review On Irisin, The Beta 3-Adrenergic Receptor, And Zinc Alpha 2-Glycoprotein’S Impact On Metabolic Health, Dawson Troutman

Honors College Theses

This thesis aims to provide insight into how Irisin, the beta 3-adrenergic receptor, and zinc alpha 2-glycoprotein can impact human metabolism. Analyzing studies on the impact these species have on thermogenesis and lipolysis help provide a clearer picture on their use in potential management of metabolic issues.

Expression And Purification Of Domain 1 Of The Cards Toxin, Dylan Andrews, Allison Woods, Ahmad Galaleldeen

Posters - 2024

Mycoplasma pneumoniae (Mp) is an atypical bacterium that is linked to various respiratory diseases such as walking pneumonia and asthma. Upon infection, Mp produces a 591-aa virulence factor known as Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX). The crystal structure of this 591-aa cytotoxin reveals a triangular molecule comprised of an N-terminal ADP-ribosylating domain and a Cterminal tandem β-trefoil domain that is responsible for vacuolation of the host’s cells. Based on structural and sequence homology to other ADP ribosylating toxins, the NAD+ binding site has been predicted, yet none of the published structures of the CARDS toxin contain NAD+. …

Tools For Biomolecular Modeling And Simulation, Xin Yang

Mathematics Theses and Dissertations

Electrostatic interactions play a pivotal role in understanding biomolecular systems, influencing their structural stability and functional dynamics. The Poisson-Boltzmann (PB) equation, a prevalent implicit solvent model that treats the solvent as a continuum while describes the mobile ions using the Boltzmann distribution, has become a standard tool for detailed investigations into biomolecular electrostatics. There are two primary methodologies: grid-based finite difference or finite element methods and body-fitted boundary element methods. This dissertation focuses on developing fast and accurate PB solvers, leveraging both methodologies, to meet diverse scientific needs and overcome various obstacles in the field.

Cyclophilin A Supports Translation Of Intrinsically Disordered Proteins And Affects Haematopoietic Stem Cell Ageing, Laure Maneix, Polina Iakova, Charles G Lee, Shannon E Moree, Xuan Lu, Gandhar K Datar, Cedric T Hill, Eric Spooner, Jordon C K King, David B Sykes, Borja Saez, Bruno Di Stefano, Xi Chen, Daniela S Krause, Ergun Sahin, Francis T F Tsai, Margaret A Goodell, Bradford C Berk, David T Scadden, André Catic

Faculty, Staff and Students Publications

Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. …

Cifa And Cifb Expression In Response To Piwi And Aub Knockdown In Jw18 D. Melanogaster Cells, Julieta Alarcon

Posters - 2024

Wolbachia is an intracellular bacterium that is known for inducing cytoplasmic incompatibility (CI) in its Drosophila melanogaster hosts. CI is characterized by embryonic death when males that express cifA and cifB genes mate with unaffected females (Shropshire, Rosenberg, and Bordenstein 2020). PIWI proteins play important roles such as germline determination, spermiogenesis, and transposon silencing (Thomson and Lin 2009). Previous studies have shown that Piwi expression decreases in a developmental window called the “Piwiless pocket” or Pilp. When Aub is depleted in the Pilp, then Piwi expression increases (Théron et al. 2018). We will determine if Piwi and Aub FANA ASO …

Characterization Of Rna Binding Proteins Regulating Axonal Localization Of Prenyl-Cdc42 Mrna, Ashley I. Loomis

Senior Theses

Following traumatic injury, axons in the peripheral nervous system (PNS) can spontaneously regenerate, albeit rather slowly. This regeneration requires messenger RNA (mRNA)-localization into and translation within the axons. One such mRNA originates from the CDC42 gene, which produces two mRNA splice variants: Prenyl-CDC42 and Palm-CDC42 encoding mRNAs. CDC42 promotes axon growth and regeneration by regulating actin filament polymerization in growth cones of axons. This plays an important role to support nerve regeneration in humans. The prenyl-Cdc42 mRNA is found in both central nervous system (CNS) and PNS axons, where it can be locally translated into CDC42 protein, which is subsequently …

Exploring Cation Exchange: Unveiling Its Significance In Biochar And Bioenergetics Applications, Gyanendra Kharel

Chemistry & Biochemistry Theses & Dissertations

Cation exchange, a cornerstone of soil chemistry and nutrient cycling, is a fundamental chemical process that occurs in soils, sediments, membranes, and other solid materials. It involves the interchange of positively charged ions, or cations, between a solid matrix and a surrounding solution. This process is crucial in various natural and engineered systems, leading to a range of applications across different fields.

This dissertation presents an extensive investigation into the applications of cation exchange in the fields of biochar and bioenergetics, encompassing three distinct aims. The first aim concentrates on the surface oxygenation of biochar through ozonization, aiming to achieve …

Decreasing The Antibiotic Survival Of Multi-Drug Resistant Gram-Positive Organisms, Areej Malik

Biomedical Sciences Theses & Dissertations

Biofilm production plays a crucial role in bacterial antibiotic tolerance and novel approaches are needed to combat it. The stringent response (SR), activated by nucleotide alarmones (pp)pGpp, is crucial for bacterial transcriptional reprogramming. In Clostridioides difficile, the SR is implicated in antibiotic survival, contributing to infection recurrence. Despite its known roles in sporulation and biofilm production in other bacterial species, the broader influence of the SR on C. difficile physiology remains undiscovered. This study deletes the C. difficile SR gene relQ, revealing the pivotal role of RelQ in regulating SR-dependent phenotypes in this organism. The absence of RelQ …

A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder

Undergraduate Research Symposium

Triple negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and disproportionately affects African American women. TNBC cells lack the common hormone receptors that many pre-existing cancer treatments target. Fortunately, metal-based complexes with thiosemicarbazone ligands have gained significant attention for their potential as anti-cancer agents. Cobalt(III) complex ([Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH]) and Copper(II) complex ([Cu(acetylethTSC)Cl]Cl•0.25C2H5OH) specifically have properties of high toxicity, which can contribute to decreased cancer cell activity. The effects of these complexes are currently being investigated on cancerous and non-cancerous breast cell lines. The cytotoxic effect of the cobalt(lll) complex and the copper(ll) complex was analyzed …

Myeloid-Derived Suppressor Cell Mitochondrial Fitness Governs Chemotherapeutic Efficacy In Hematologic Malignancies, Saeed Daneshmandi, Jee Eun Choi, Qi Yan, Cameron R. Macdonald, Manu Pandey, Mounika Goruganthu, Nathan Roberts, Prashant K. Singh, Richard M. Higashi, Andrew N. Lane, Teresa W-M Fan, Jianmin Wang, Philip L. Mccarthy, Elizabeth A. Repasky, Hemn Mohammadpour

Markey Cancer Center Faculty Publications

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprogram- ing, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of …

Blocking The Dimerization Of Polyglutamine-Expanded Androgen Receptor Protects Cells From Dht-Induced Toxicity By Increasing Ar Turnover, Allison Lisberg, Yuhong Liu, Diane E. Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular degenerative disease caused by a polyglutamine expansion in the androgen receptor (AR). This mutation causes AR to misfold and aggregate, contributing to toxicity in and degeneration of motor neurons and skeletal muscle. There is currently no effective treatment or cure for this disease. The role of an interdomain interaction between the amino- and carboxyl-termini of AR, termed the N/C interaction, has been previously identified as a component of androgen receptor-induced toxicity in cell and mouse models of SBMA. However, the mechanism by which this interaction contributes to disease pathology is unclear. …

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

A Review On Role Of Bacillus Species In Bio-Calcification: A Way Forward In Carbonate Precipitation, Ardil Bin Mansoor, Sheema Yousaf, Amna Gulzar, Ramsha Iqbal, Aisha Waheed Qurashi

Journal of Bioresource Management

Bio-calcification, also known as microbiologically induced calcite precipitation, is a phenomenon involving the activity of the enzyme urease. A large number of soil microorganism exhibit urease-producing ability. The main purpose of this review article is to signify the calcium carbonate bio-precipitation by Bacillus species including Lysinibacillus sphaericus and Bacillus subtilis. They both precipitated calcite and the shape and size depending on the external and internal conditions like the type of culture medium and the bacterial strains that were used. The research group increased attentions toward MICP (microbial-induced carbonated precipitation) because of its eco-friendly application. Different bacterial strains had been …

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

Altered Lipid Metabolism In Apc-Driven Colorectal Cancer: The Potential For Therapeutic Intervention, Courtney O. Kelson, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Altered lipid metabolism is a well-recognized feature of solid cancers, including colorectal cancer. In colorectal cancer, upregulation of lipid metabolism contributes to initiation, progression, and metastasis; thus, aberrant lipid metabolism contributes to a poor patient outcome. The inactivating mutation of APC, a vital tumor suppressor in the Wnt signaling pathway, is a key event that occurs early in the majority of colorectal cancer cases. The potential crosstalk between lipid metabolism and APC-driven colorectal cancer is poorly understood. This review collectively highlights and summarizes the limited understanding between mutations in APC and the upregulation of Wnt/beta- catenin signaling and lipid metabolism. …

Β-Cyclodextrin-Enzalutamide Self-Assembly Complexes For Prostate Cancer Therapy, Meghana Kolli, Rahul Tiwari, Subhash C. Chauhan, Yonghong Zhang, Neeraj Chauhan, Alba C. M, Murali Yallapu

Research Symposium

Background:Castrate circumstances brought on by therapy give rise to castrationresistant prostate cancer (CRPC), which thereafter develops androgen receptor (AR) resistance. AR inhibitors are frequently used to obstruct AR translocation in cells that overexpress AR and slow the progression of cancer by reducing the number of AR receptors that are accessible. In comparison to Bicalutamide, a first-generation AR inhibitor, the hydrophobic drug Enzalutamide has demonstrated higher effectiveness. We investigate Enzalutamide as a viable option for the formation of self-assembly complexes because AR downregulation is still the major treatment for CRPC.

Methods:Enz-loaded self-assembly complexes (enz-β-CD) formulation was developed using solvent …

Trip13’S Crucial Role In Pancreatic Cancer Progression, Swati Dhasmana, Anupam Dhasmana, Stella Rios, Iris A. Enriquez-Perez, Sheema Khan, Farrukh Afaq, Upender Manne, Murali M. Yallapu, Subhash Chauhan

Research Symposium

Background: Pancreatic cancer, characterized by its high mortality rate, stands as one of the most aggressive cancer forms. The projected surge in pancreatic cancer-related deaths, making it the second leading cause in the United States by 2030, underscores the urgency for effective early screening tools. This study employs data mining methods to scrutinize bioinformatic data surrounding TRIP13. Examining differential expression across various cancers, correlating TRIP13 expression with pancreatic cancer stages, exploring associations with common cancer genes, and analyzing overall survival rates constitute the core investigations. Integrated with molecular biology techniques, the study further quantifies TRIP13 expression in progressive pancreatic cancer …

Targeting Mycobacterial Efflux System For Combating Anti-Microbial Resistance, Arathi Radhakrishnan, Raj Kishor Kapardar, Rajpal Srivastav

Research Symposium

Background: The drug resistance in the microbes is a serious concern in medicine. Along with intrinsic factors, extrinsic factors like unprescribed usage of drugs are the contributing factors. The drug tolerance has led to the emergence of superbugs. Mycobacterial species utilize an array of multidrug efflux mechanisms linked to intrinsic and acquired antibiotic resistance. Understanding molecular mechanisms regulating efflux could reveal new therapeutic targets and strategies. Our study is aimed to target regulators of efflux Mycobacterial transporter.

Methods: Using the reference mycobacterial strain, antibiotic sensitivity was first profiled by minimal inhibitory concentration assays across a panel of antimicrobials, followed by …

Proteomic Analysis Of Stress Associated Factor Overexpression In Hepatocellular Carcinoma, Mohammad Shabir Hussain, Sophia Leslie, Amayrani Sanchez, Samantha Lopez, Kyle Doxtater, Manish Kumar Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) constitutes a substantial portion, accounting for 85% to 90% of liver cancers worldwide. Notably, within the Hispanic population, liver cancer mortality rates are notably higher, particularly evident in regions like the South Texas Rio Grande Valley (RGV), where nearly 90% of the populace is Latino/Hispanic. This region grapples with poverty affecting nearly 30% of its residents, coupled with elevated rates of obesity, diabetes, and low-income households, thereby fostering a prevalent environment of stress. Stress can profoundly impact cancer outcomes by compromising immune functionality and triggering inflammatory responses, potentially impairing surveillance against oncogenic triggers. The activation of …

Piperlongumine Nanoformulation Attenuates Pancreatic Tumor Desmoplasia And Alter Tumor Immune Responses, Vivek Kumar Kashyap, Neeraj Chauhan, Mohammed Sikander, Eswara N. H. K. Ghali, Bilal Hafeez, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

Research Symposium

Pancreatic cancer (PanCa) is characterized by lack of early diagnosis, poor response to available therapeutic modalities and chemoresistance. Gemcitabine (GEM) is currently considered the most effective therapy for PanCa; however, it shows only a marginal survival benefit of 6 months. This poor drug response has been attributed to desmoplasia, causes suboptimal drug delivery, alters tumor microenvironment (TME), which includes tumor surrounding blood vessels, fibroblasts, immune cells, extracellular matrix, and other signaling molecules and induces chemo-resistance in tumors. To overcome these existing issues associated with chemotherapy, identification and development of novel therapeutic modalities are a pressing need. Piperlongumine (PL) is a …

Coomassie Brilliant Blue Dye As A Method For Analyzing Fracture Markings In Bone, Abigail Hoffmeister, David Harutunyan, Matthew Aizawa, Everett Baker, Brandon Mendoza, Chase Freeman, Siran Iskanian

Seaver College Research And Scholarly Achievement Symposium

Coomassie Brilliant Blue Dye is a dye commonly used to stain proteins. Because of its ability to adhere to proteins, this research has focused on perfecting a method of dyeing a fractured flat bone in order to most accurately observe and analyze fracture markings within the trabecular layer. Stereoscopic microscopy was the chosen technique of analysis for this research because of its proven effectiveness in glass and ceramic fractography to observe varying depths. In order to most effectively apply stereoscopic microscopy to this research, the following variables were manipulated to maximize color contrast in the trabecular layer in order to …

Is Edna Concentration In Staphylococcus Aureus Biofilm Affected By Nanotube Coating?, Brooklyn Z. Jones, Bradford K. Berges, Lucy C. Bowden

Library/Life Sciences Undergraduate Poster Competition 2024

1st Place Oral Presentation

• ~30% of artificial joint failure is caused by infection1

• 80-100% of patients who receive external fixator pins will experience an infection2

• Most of these infections are caused by Staphylococcus aureus

• S. aureus forms biofilms (surface-associated collections of bacteria) that are extremely difficult to treat

• eDNA provides structure and protection to the biofilm

Changes In Environmental Conditions Affect The Two Isoforms Of Snap-25 Differently, Joseph Jackson, Dixon J. Woodbury, Tanner M. Blocker, Samuel W. Shumway, Jarom S. Sumsion, Thomas Weed, Jason Carlson, Nathan Mumford, Ryan Poland

Library/Life Sciences Undergraduate Poster Competition 2024

In the brain, neurons communicate via releasing and detecting neurotransmitters. Release occurs through exocytosis, following fusion of synaptic vesicles to neuronal cell membranes. This process is driven by formation of a dynamic quaternary protein structure known as the SNARE complex. SNAP-25 contributes two alpha helical domains to this complex. Neurons express SNAP-25 in two distinct isoforms, SNAP-25A (25A) and SNAP-25B (25B). These two isoforms vary by only 9 amino acids and are expressed differently depending on brain region and the developmental stage of the neuron [1]. The primary structures of 25A and 25B and their effect on SNARE complex formation …

Using Chimeric Autoantigen Receptor (Caar) T Cells To Eliminate Autoreactive B Cells In Autoimmune Diseases, Abigail Cheever, Chloe Kang, Hunter Lindsey, Mackenzie Hansen, Kim O'Neill, Scott Weber

Library/Life Sciences Undergraduate Poster Competition 2024

• Graves’ disease (GD) is an antibody-mediated autoimmune disease affecting the thyroid and causes hyperthyroidism
• 4th most common autoimmune disease in the US
• Autoreactive B cells produce anti-TSHR antibodies (TRAbs) which mimic thyroid stimulating hormone (TSH) and chronically stimulate thyroid cells causing hyperthyroidism
• There currently is no treatment which addresses the root cause of the disease

Effects Of Post-Translational Histone Modifications On Transcription Rate, Jacob Hunter, Steven Johnson, Aaron Bohn, Sarah Ricks, Sarah Hodson, David Bates, Steven M. Johnson

Library/Life Sciences Undergraduate Poster Competition 2024

DNA structure and organization in eukaryotic cells significantly impacts the regulation of geneexpression, cellular properties and overall behavior. At the most fundamental unit of this organization,~147 bp of DNA wraps 1.7 times around a histone octamer core, forming a collective unit called thenucleosome. Positioning and occupancy of nucleosomes around promoter elements of genes is knownto be a strong regulator of transcription in eukaryotic nuclei. Post-translational modifications (PTM’s) tothe protruding N-terminal tails of histone proteins are known to influence chromatin structure and thusgene expression; however, relatively little is known about the residual effect of histone PTM’s ontranscription rate.

Design To Data For Mutants Of Β-Glucosidase B From Paenibacillus Polymyxa: E26k, I170y, And V398n, Carter Ahlstedt, Annika Bennett, Daniel Kaluka

Lux et Fides: A Journal for Undergraduate Christian Scholars

Protein modeling aids in developing novel protein configurations that are critical in, for example, the pharmaceutical and environmental industries. However, the predictive capabilities of the protein modeling algorithms are limited due to a lack of experimental data on structure and function. To bridge this gap, Seigel Lab at UC Davis developed the Design to Data (D2D) program to catalog thermal stability and catalytic efficiency data sets on β-glucosidase B (BglB) variants. Over 300 BglB variants have been characterized. However, there are over 8400 possible BglB single-point mutations. We utilized Foldit software to design BglB mutants E26K, I170Y, and V398N. The …

Design Of The Strive-Ipf Trial- Study Of Therapeutic Plasma Exchange, Rituximab, And Intravenous Immunoglobulin For Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Tejaswini Kulkarni, Gerard J Criner, Daniel J Kass, Ivan O Rosas, Mary Beth Scholand, Daniel F Dilling, Ross Summer, Steven R Duncan

Faculty, Staff and Students Publications

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

METHODS: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population …