Other Biochemistry, Biophysics, and Structural Biology Commons^™

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair

Dissertations & Theses (Open Access)

KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …

Design, Synthesis, And Analysis Of Paired Coiled-Coil Peptidic Molecular Building Blocks Used For Linearly Controlled Self-Assembly Of Α-Helical Coiled-Coil Heterodimer Peptide Pairs, Jason Distefano

Chemistry Theses

Molecular building blocks are fundamental to biological synthesis and processes and have been utilized in advanced materials, drugs and drug delivery systems, and biotechnology. Proteins have been used as molecular building blocks for the construction of complex, well-ordered structures. Coiled-coil protein domains are essential subunits used for the oligomerization of protein complexes, gene expression, and structural elements of biological materials. The synthesis and assembly of proteins utilizing coiled-coil motifs are of great scientific interest due to their potential applications in disease treatment, biomechanical motors, nanoscale delivery systems, etc. However, assembling protein complexes with specific morphology is still challenging because …

Annual Faculty Research Symposium 2022, Oakwood University

Proceedings

No abstract provided.

Als-Associated Kif5a Mutations Abolish Autoinhibition Resulting In A Toxic Gain Of Function, Desiree M. Barron, Adam R. Fenton, Sara Saez-Atienzar, Anthony Giampetruzzi, Aparna Sreeram, Shankaracharya, Pamela J. Keagle, Victoria R. Doocy, Nathan J. Smith, Eric W. Danielson, Megan Andresano, Mary C. Mccormack, Jaqueline Garcia, Valérie Bercier, Ludo Van Den Bosch, Jonathan R. Brent, Claudia Fallini, Brian J. Traynor, Erica L.F. Holzbaur, John E. Landers

Biochemistry -- Faculty Publications

Understandingthepathogenicmechanismsof diseasemutations is critical toadvancingtreatments.ALS-associated mutations in the gene encoding the microtubulemotor KIF5A result in skipping of exon 27 (KIF5ADExon27) and the encoding of a protein with a novel 39 amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C terminus of mutant KIF5A results in a constitutively active state. Furthermore,mutant KIF5A possesses altered protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative …

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 …

Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosis, Yukako Kayashima, Connor A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Ed Harris

Department of Biochemistry: Faculty Publications

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe^−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe^−/− mice carrying Aath5 covering the Stab2 …

Reduction Of Stabilin-2 Contributes To A Protection Against Atherosclerosisstabilin, Yukako Kayashima1*,, Conner A. Clanton, Amanda M. Lewis, Xinghui Sun, Sylvia Hiller, Phillip Huynh, Jennifer Wilder, John Hagaman, Feng Li, Nobuyo Maeda-Smithies, Edward N. Harris

Department of Biochemistry: Faculty Publications

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe^−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe^−/− mice carrying Aath5 covering the Stab2^DBA allele …

Disruption Of Claudin-Made Tight Junction Barriers By Clostridium Perfringens Enterotoxin: Insights From Structural Biology, Chinemerem P. Ogbu, Sourav Roy, Alex J. Vecchio

Department of Biochemistry: Faculty Publications

Claudins are a family of integral membrane proteins that enable epithelial cell/cell interactions by localizing to and driving the formation of tight junctions. Via claudin self-assembly within the membranes of adjoining cells, their extracellular domains interact, forming barriers to the paracellular transport of small molecules and ions. The bacterium Clostridium perfringens causes prevalent gastrointestinal disorders in mammals by employing an enterotoxin (CpE) that targets claudins. CpE binds to claudins at or near tight junctions in the gut and disrupts their barrier function, potentially by disabling their assembly or via cell signaling means—the mechanism(s) remain unclear. CpE ultimately destroys claudin-expressing cells …

A Glass Bead Semi‑Hydroponic System For Intact Maize Root Exudate Analysis And Phenotyping, Martha G. Lopez-Guerrero, Peng Wang, Felicia Phares4, Daniel P. Schachtman, Sophie Alvarez, Karin Van Dijk

Department of Biochemistry: Faculty Publications

Background: Although there have been numerous studies describing plant growth systems for root exudate collection, a common limitation is that these systems require disruption of the plant root system to facilitate exudate collection. Here, we present a newly designed semi-hydroponic system that uses glass beads as solid support to simulate soil impedance, which combined with drip irrigation, facilitates growth of healthy maize plants, collection and analysis of root exudates, and phenotyping of the roots with minimal growth disturbance or root damage.

Results: This system was used to collect root exudates from seven maize genotypes using water or 1 mM CaCl …

Sesamum Indicum Diet Prevents Hyperlipidemia In Experimental Rats, Muinat M. Adeyanju, Idris A. Saheed, Oluwaseun I. Oyelekan, Taiwo A. Dele-Osibanjo, Ayodeji A. Adelegan, Adekunle J. Raimi, Samuel O. Olalekan, Olugbenga S. Alabi, Khadijat M. Alli

Department of Biochemistry: Faculty Publications

Cardiovascular diseases and metabolic complications caused by hyperlipidemia are the leading cause of death globally. In this study, the hypolipidemic potency of Sesamum indicum (SI) seeds was investigated. Of the thirty-five (35) male rats used in the study, five (5) were randomly selected for baseline measurements and thirty (30) were fed high fat diet (HFD) for four (4) weeks before random assignment into three (3) groups. The experimental group was treated with 50% SI seed, the positive control group was given a hypolipidemic drug, atorvastatin (5 mg/kg/day) while the untreated group served as the negative control. With SI administration, the …

Role Of Specialized Pro-Resolving Mediators In Reducing Neuroinflammation In Neurodegenerative Disorders, Jana Ponce, Arzu Ulu, Corrine Hanson, Erin Cameron-Smith, Jenna Wuebker, John Bertoni, Alfred Fisher, Ka-Chun Siu, Vivien Marmelat, Jiri Adamec, Danish Bhatti

Department of Biochemistry: Faculty Publications

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders that affect millions of individuals worldwide. As incidence of these conditions increases with age, there will undoubtedly be an increased prevalence of cases in the near future. Neuroinflammation is a hallmark in the development and progression of neurodegenerative diseases and prevention or resolution of chronic neuroinflammation may represent a novel approach to treatment. The present review highlights the potential of the anti-inflammatory and pro-resolving effects of polyunsaturated fatty acid (PUFA)- derived mediators (Specialized Pro-resolving Mediators—SPM) in neurodegenerative disorders. PUFA-derived SPM are biosynthesized in response to chemicals produced from acute inflammatory …

Two Heads Are Better Than One: Current Landscape Of Integrating Qsp And Machine Learning, Tongli Zhang, Ioannis P. Androulakis, Peter Bonate, Limei Cheng, Tomáš Helikar, Jaimit Parikh, Christopher Rackauckas, Kalyanasundaram Subramanian, Carolyn R. Cho

Department of Biochemistry: Faculty Publications

Quantitative systems pharmacology (QSP) modeling is applied to address essential questions in drug development, such as the mechanism of action of a therapeutic agent and the progression of disease. Meanwhile, machine learning (ML) approaches also contribute to answering these questions via the analysis of multi-layer ‘omics’ data such as gene expression, proteomics, metabolomics, and high-throughput imaging. Furthermore, ML approaches can also be applied to aspects of QSP modeling. Both approaches are powerful tools and there is considerable interest in integrating QSP modeling and ML. So far, a few successful implementations have been carried out from which we have learned about …

Functional Foods: Promising Therapeutics For Nigerian Children With Sickle Cell Diseases, Oladeji John Alabi, Fikayo Noah Adegboyega, Dolapo Samuel Olawoyin, Oluwakemi Arinola Babatunde

Department of Biochemistry: Faculty Publications

Sickle cell disease (SCD), also known as sickle cell anemia (SCA) is one of the structural hemoglobinopathies that occurs due to a single nucleotide mutation from GAG to GTG, which changes the amino acid of a β-globin chain of hemoglobin (Hb) from glutamate to valine. This singular mutation results to disorderliness in red blood cells (RBCs) with advent of changes in RBC morphology and other pathological conditions. In the 1980s, intermittent red blood cell transfusions, opioids, and penicillin prophylaxis were the only available therapy for SCA and were commonly reserved for acute, life threatening complications. So far, the US Food …

Development, Structure, And Mechanism Of Synthetic Antibodies That Target Claudin And Clostridium Perfringens Enterotoxin Complexes, Benjamin J. Orlando, Pawel K. Dominik, Sourav Roy, Chinemerem P. Ogbu, Satchal K. Erramilli, Anthony A. Kossiakoff, Alex J. Vecchio

Department of Biochemistry: Faculty Publications

Strains of Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflicts humans and domesticated animals, causing prevalent gastrointestinal illnesses. CpE’s C-terminal domain (cCpE) binds cell surface receptors, followed by a restructuring of its N-terminal domain to form a membranepenetrating β-barrel pore, which is toxic to epithelial cells of the gut. The claudin family of membrane proteins are known receptors for CpE and also control the architecture and function of cell-cell contacts (tight junctions) that create barriers to intercellular molecular transport. CpE binding and assembly disables claudin barrier function and induces cytotoxicity via β-pore formation, disrupting gut homeostasis; however, a structural …

Metabolic Synergy Between Human Symbionts Bacteroides And Methanobrevibacter, Jennie L. Catlett, Sean Carr, Mikaela Cashman, Megan D. Smith, Mary Walter, Zahmeeth Sakkaff, Christine A. Kelley, Massimiliano Pierobon, Myra B. Cohen, Nicole R. Buan

Department of Biochemistry: Faculty Publications

ABSTRACT Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the Gram-negative heterotrophic bacterium Bacteroides thetaiotaomicron and the methanogenic archaeon Methanobrevibacter smithii, are proposed to have a synergistic metabolic relationship. Both organisms play vital roles in human gut health; B. thetaiotaomicron assists the host by fermenting dietary polysaccharides, whereas M. smithii consumes end-stage fermentation products and is hypothesized to relieve feedback inhibition of upstream microbes such as B. thetaiotaomicron. To study their metabolic interactions, we defined and optimized a coculture system and used software testing …

The Follicular Lymphoma Epigenome Regulates Its Microenvironment, Rada Amin, Mounia S. Braza

Department of Biochemistry: Faculty Publications

Follicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse …

Feedlot Diets Containing Different Starch Levels And Additives Change The Cecal Proteome Involved In Cattle’S Energy Metabolism And Inflammatory Response, Leone Campos Rocha, Andrey Sávio De Almeida Assunção, Renata Aparecida Martins, Victor Valério De Carvalho, Alexandre Perdigão2, Marília Afonso Rabelo Buzalaf, Jiri Adamec, Camila Pereira Braga, Danilo Domingues Millen, José Cavalcante Souza Vieira, Pedro De Magalhães Padilha

Department of Biochemistry: Faculty Publications

Diets for feedlot cattle must be a higher energy density, entailing high fermentable carbohydrate content. Feed additives are needed to reduce possible metabolic disorders. This study aimed to analyze the post-rumen effects of different levels of starch (25%, 35%, and 45%) and additives (monensin or a blend of essential oils and exogenous α-amylase) in diets for Nellore feedlot cattle. The cecum tissue proteome was analyzed via two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and then differentially expressed protein spots were identified with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The use of blends of essential oils associated with α-amylase as a feed additive promoted …

Recognition Of Extracellular Dna By Type Iv Pili Promotes Biofilm Formation By Clostridioides Difficile, Leslie A. Ronish, Ben Sidner, Yafan Yu, Kurt H. Piepenbrink

Department of Biochemistry: Faculty Publications

Clostridioides difficile is a Gram-positive bacillus, which is a frequent cause of gastrointestinal infections triggered by the depletion of the gut microbiome. Because of the frequent recurrence of these infections after antibiotic treatment, mechanisms of C. difficile persistence and recurrence, including biofilm formation, are of increasing interest. Previously, our group and others found that type IV pili, filamentous helical appendages polymerized from protein subunits, promoted microcolony and biofilm formation in C. difficile. In Gram-negative bacteria, the ability of type IV pili to mediate bacterial self-association has been explained through interactions between the pili of adjacent cells, but type …

Spatially Controlled Monolayers For Electrically Switchable Biomolecule Detection, Eduard Lukhmanov

Theses, Dissertations and Capstones

The development of biosensors that are low-waste, highly stable, and possess an ability to be interchanged between capturing and non-capturing configurations is promising for the biodetector field. Stable packing and attachment of the sensor, the ability to create an interchangeable detecting probe of interest relatively easily, and dynamic control of the probe via a reversible bias can provide for that. With the set goals to control all those properties, DNA-dendron conjugate molecules were designed, synthesized in solution, purified, and utilized to make self-assembled monolayers of single-stranded DNA on gold. To be able to manipulate the conjugates’ sensing qualities in the …

Analysis Of The Antimicrobial Activity Of The Novel Chemotherapeutic Drug, Tpp1, Against Pseudomonas Aeruginosa And The Hydrogel Delivery Of Water-Soluble Antimicrobial Compounds, Alex Gasper

Senior Independent Study Theses

Cancer is one of the leading causes of death in the world, and it is commonly linked with bacterial infections that often complicate treatments. Recently, chemotherapeutics have been developed that are able to act as anti-cancer agents using delocalized lipophilic cations (DLCs) that are able to specifically target mitochondrial membranes of cancer cells. TPP1 is a newly developed chemotherapeutic drug that has activity against bladder cancer and melanoma cell lines in vitro. In order to determine if TPP1 has antimicrobial activity, TPP1 was tested against a common bacteria, Pseudomonas aeruginosa, to determine if antimicrobial activity was present. This testing was …

Arginine Catabolism And Polyamine Biosynthesis Pathway Disparities Within Francisella Tularensis Subpopulations, Yinshi Yue, Bhanwar Lal Puniya, Tomáš Helikar, Benjamin Girardo, Steven H. Hinrichs, Marilyn A. Larson

Department of Biochemistry: Faculty Publications

Francisella tularensis is a highly infectious zoonotic pathogen with as few as 10 organisms causing tularemia, a disease that is fatal if untreated. Although F. tularensis subspecies tularensis (type A) and subspecies holarctica (type B) share over 99.5% average nucleotide identity, notable differences exist in genomic organization and pathogenicity. The type A clade has been further divided into subtypes A.I and A.II, with A.I strains being recognized as some of the most virulent bacterial pathogens known. In this study, we report on major disparities that exist between the F. tularensis subpopulations in arginine catabolism and subsequent polyamine biosynthesis. The genes …

Addressing Barriers In Comprehensiveness, Accessibility, Reusability, Interoperability And Reproducibility Of Computational Models In Systems Biology, Anna Niarakis, Dagmar Waltemath, James Glazier, Falk Schreiber, Sarah M. Keating, David Nickerson, Claudine Chaouiya, Anne Siegel, Vincent Noël, Henning Hermjakob, Tomáš Helikar, Sylvain Soliman, Laurence Calzone

Department of Biochemistry: Faculty Publications

Computational models are often employed in systems biology to study the dynamic behaviours of complex systems. With the rise in the number of computational models, finding ways to improve the reusability of these models and their ability to reproduce virtual experiments becomes critical. Correct and effective model annotation in community-supported and standardised formats is necessary for this improvement. Here,we present recent efforts toward a common framework for annotated, accessible, reproducible and interoperable computational models in biology, and discuss key challenges of the field.

Scientists from different systems biology fields have long been developing community-driven guidelines and best practices for annotation, …

Building Digital Twins Of The Human Immune System: Toward A Roadmap, Reinhard Laubenbacher, Anna Niarakis, Tomas Helikar, G. An, B. Shapiro, R. S. Malik-Sheriff, T. J. Sego, P. Macklin, J. A. Glazier

Department of Biochemistry: Faculty Publications

Digital twins, customized simulation models pioneered in industry, are beginning to be deployed in medicine and healthcare, with some major successes, for instance in cardiovascular diagnostics and in insulin pump control. Personalized computational models are also assisting in applications ranging from drug development to treatment optimization. More advanced medical digital twins will be essential to making precision medicine a reality. Because the immune system plays an important role in such a wide range of diseases and health conditions, from fighting pathogens to autoimmune disorders, digital twins of the immune system will have an especially high impact. However, their development presents …

Endothelial Cell-Specific Deletion Of A Microrna Accelerates Atherosclerosis, Dafeng Yang, Stefan Haemmig, Jingshu Chen, Michael Mccoy, Henry S. Cheng, Haoyang Zhou, Daniel Pérez-Cremades, Xiao Cheng, Xinghui Sun, Jorge Haneo-Mejia, Shamsudheen K. Vellarikkal, Rajat M. Gupta, Victor Barrera, Mark W. Feinberg

Department of Biochemistry: Faculty Publications

Background and aims: Chronic vascular endothelial inflammation predisposes to atherosclerosis; however, the cell-autonomous roles for endothelial-expressing microRNAs (miRNAs) are poorly understood in this process. MiR-181b is expressed in several cellular constituents relevant to lesion formation. The aim of this study is to examine the role of genetic deficiency of the miR-181b locus in endothelial cells during atherogenesis.

Methods and Results: Using a proprotein convertase subtilisin/kexin type 9 (PCSK9)-induced atherosclerosis mouse model, we demonstrated that endothelial cell (EC)-specific deletion of miR-181a2b2 significantly promoted atherosclerotic lesion formation, cell adhesion molecule expression, and the influx of lesional macrophages in the vessel wall. Yet, …

Fish Oil Intake During Gestation And Lactation Attenuated Stz-Induced Diabetes Inmale Offspring Via Activation Of Brown Fat And Modulating Oxylipin Profile, Rong Fan, Shalom Thomas, Mikyoung You, Zhuoheng Li, Brandt Bessell, Bhanwar Lal Puniya, Tomáš Helikar, Zhenhua Liu, Soonkyu Chung

Department of Biochemistry: Faculty Publications

Fish oil (FO) has been demonstrated to activate brown thermogenesis and attenuate inflammation in the brown adipose tissue (BAT). Previously, we have reported thatmaternal FO supplementation promotes BAT activity of the weaned mice pups. However, whether maternal FO intake could confer sustainable metabolic benefits to offspring remains uncovered. Therefore, this study aimed to determine the differential impact of maternal FO during pregnancy versus lactation on BAT transcriptome and evaluate the role of bioactive lipid metabolites derived from maternal FO supplementation on the extended metabolic benefits of older pups in the context of type 1 diabetes (T1D).

Conclusions: Our results suggested …

Coordination Of Metal Center Biogenesis In Human Cytochrome C Oxidase, Eva Nývltová, Jonathan Dietz, Javier Seravalli, Oleh Khalimonchuk, Antoni Barrientos

Department of Biochemistry: Faculty Publications

Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3- copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the …

The Role Of Irf-1 In Spontaneous Mouse Glioma, Aakash B. Vaidya

Theses and Dissertations

Glioblastoma Multiforme has been shown to be one of the deadliest primary brain cancers. One of the reasons why GBM is so deadly, is a unique immunosuppressive tumor microenvironment that promotes GBM growth and progression. Both astrocyte and microglia have been implicated in immunosuppression. In this study, we explored the role of Interferon Regulatory Factor 1 (IRF-1) in astrocytes and glioma cells on the growth of spontaneous glioma tumors. IRF-1 is regulated by the JAK/STAT pathway and induces expression of Programmed death ligand 1 (PD-L1). PD-L1 downregulates immune responses to glioma. We found that IRF-1 had no effect on spontaneous …

A Link Between Methylglyoxal And Heart Failure During Hiv-1 Infection, Prasanta K. Dasg, Fadhel A. Alomar, Jesse L. Cox, Joellyn Mcmillan, Bryan T. Hackfort, Edward Makarov, Brenda Morsey, Howard S. Fox, Howard E. Gendelman, Santhi Gorantla, Keshore R. Bidasee

Department of Biochemistry: Faculty Publications

Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg- Prkdc^scidIl2rg^tm1Wjl/SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma …