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Loyola University Chicago

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Articles 1 - 30 of 175

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

In Silico Binding Of 2-Aminocyclobutanones To Sars-Cov-2 Nsp13 Helicase And Demonstration Of Antiviral Activity, Thahani S. Habeeb Mohammad, Yash Gupta, Cory T. Reidl, Vlad Nicolaescu, Haley Gula, Ravi Durvasula, Prakasha Kempaiah, Daniel P. Becker Ph.D. Mar 2023

In Silico Binding Of 2-Aminocyclobutanones To Sars-Cov-2 Nsp13 Helicase And Demonstration Of Antiviral Activity, Thahani S. Habeeb Mohammad, Yash Gupta, Cory T. Reidl, Vlad Nicolaescu, Haley Gula, Ravi Durvasula, Prakasha Kempaiah, Daniel P. Becker Ph.D.

Chemistry: Faculty Publications and Other Works

The landscape of viral strains and lineages of SARS-CoV-2 keeps changing and is currently dominated by Delta and Omicron variants. Members of the latest Omicron variants, including BA.1, are showing a high level of immune evasion, and Omicron has become a prominent variant circulating globally. In our search for versatile medicinal chemistry scaffolds, we prepared a library of substituted α-aminocyclobutanones from an α-aminocyclobutanone synthon (11). We performed an in silico screen of this actual chemical library as well as other virtual 2-aminocyclobutanone analogs against seven SARS-CoV-2 nonstructural proteins to identify potential drug leads against SARS-CoV-2, and more broadly against coronavirus …

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Role Of Micrornas In Intestinal Inflammation And Barrier Homeostasis After Alcohol And Burn Injury, Caroline J. Herrnreiter Jan 2023

Role Of Micrornas In Intestinal Inflammation And Barrier Homeostasis After Alcohol And Burn Injury, Caroline J. Herrnreiter

Dissertations

MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression. Within the intestinal epithelium, miRNAs play a critical role in gut homeostasis and aberrant miRNA expression has been implicated in various disorders associated with intestinal inflammation and barrier disruption. In this study, we sought to profile changes in intestinal epithelial cell miRNA expression after alcohol and burn injury and elucidate their impact on inflammation and barrier integrity. In a more targeted approach, we began by focusing on anti-inflammatory miRNAs that, when downregulated, could exacerbate inflammation and result in intestinal barrier disruption. Using a mouse model of acute ethanol intoxication …

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Characterizing The Dynamic Localization Of Cmi In Early Drosophila Development, Asra Habibullah Jan 2023

Characterizing The Dynamic Localization Of Cmi In Early Drosophila Development, Asra Habibullah

Master's Theses

The COMPASS-like family of lysine methyltransferases, MLR/MLX complexes, are epigenetic regulators that are essential for normal development through the methylation of the fourth lysine residue on histone 3 (H3K4), a universal epigenetic mark associated with active transcription. This family of complexes is highly conserved from yeast to mammals and the genes encoding the human MLR complexes have been associated with various developmental diseases and cancers (Dingwall and Fagan, 2019). In D. melanogaster, the enzymatic methyltransferase core of this complex is composed of two proteins: Cara Mitad (Cmi, also known as Lpt) and Trithorax-related (Trr). Although these proteins have been shown …

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Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied Jan 2023

Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied

Master's Theses

Bcl2-associated athanogene-3 (BAG3) is a pro-autophagy co-chaperone that we havepreviously shown localizes to the cardiac sarcomere and is critical for proteostasis and maintenance of normal sarcomeric function. Indeed, BAG3 loss in heart failure (HF) results in accumulation of ubiquitinated sarcomeric proteins, and depressed maximum force generating capacity (Fmax). However, how BAG3 is regulated in the cell is not well understood, with uncertainty about its structure and proteoforms. During our analysis of human heart tissue, BAG3 appears as a “doublet”, with one band at 74 kDa (BAG3-Z) and a second at a higher 85 kDa (BAG3-FL). Previous studies hypothesized the full-length …

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Dynamic Control Of The Cardiac Calcium Pump, Sean Robert Cleary Jan 2023

Dynamic Control Of The Cardiac Calcium Pump, Sean Robert Cleary

Dissertations

The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ into the endoplasmic reticulum of cells to establish a reservoir for Ca2+ signaling. In the heart, the activity of this transporter is tightly controlled via direct interactions with two competing regulatory micropeptides: phospholamban (PLB) and dwarf open reading frame (DWORF). PLB inhibits SERCA, while DWORF activates SERCA. These competing interactions determine cardiac performance by modulating the Ca2+ signals that drive the contraction/relaxation cycle. Previous studies indicated these SERCA-micropeptide interactions are Ca2+-sensitive; SERCA binds PLB more avidly at low cytoplasmic [Ca2+] but binds DWORF better when [Ca2+] is high. Here, FRET-microscopy demonstrated that this …

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The Impacts Of Framework Mutations On Steady-State Kinetics Of An Aldolase Abzyme, Charles Andrew Mettler Oct 2022

The Impacts Of Framework Mutations On Steady-State Kinetics Of An Aldolase Abzyme, Charles Andrew Mettler

Master's Theses

During affinity maturation, antibodies acquire point mutations that lead to enhanced binding strength to a particular ligand while simultaneously becoming more conformationally restricted as they become increasingly complementary to their ligand’s electrostatic geometry. This property has catalytic potential in transition-state (TS) stabilization whereby kinetic barriers (i.e., the energetic gap between the substrate and its TS) are reduced and reaction rates are enhanced. This basic mechanism is thought to underlie the majority of the rate enhancement observed for enzymes. A key integration of antibody binding specificity and strength with enzymatic catalytic strategy is the development of catalytic antibodies (“abzymes”). Abzymes are …

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Structural And Transient Kinetic Analysis On Mechanism-Based Inactivators Of Human Ornithine Aminotransferase, Arseniy Butrin Oct 2022

Structural And Transient Kinetic Analysis On Mechanism-Based Inactivators Of Human Ornithine Aminotransferase, Arseniy Butrin

Dissertations

HCC, Hepatocellular carcinoma, MBI, Mechanism-based inactivator, OAT, Ornithine Aminotransferase

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The Roles Of A Probiotic Exopolysaccharide In Breast Cancer, Mai Rachel Nguyen Oct 2022

The Roles Of A Probiotic Exopolysaccharide In Breast Cancer, Mai Rachel Nguyen

Dissertations

breast cancer, exopolysaccharide, probiotic

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Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee Jul 2022

Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee

Engineering Science Faculty Publications

Novel stimulation protocols for neuromodulation with magnetic fields are explored in clinical and laboratory settings. Recent evidence suggests that the activation state of the nervous system plays a significant role in the outcome of magnetic stimulation, but the underlying cellular and molecular mechanisms of state-dependency have not been completely investigated. We recently reported that high frequency magnetic stimulation could inhibit neural activity when the neuron was in a low active state. In this paper, we investigate state-dependent neural modulation by applying a magnetic field to single neurons, using the novel micro-coil technology. High frequency magnetic stimulation suppressed single neuron activity …

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Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah Mar 2022

Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing …

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Abl2 Promotes Alcohol-Associated Liver Disease Via Ppar Gamma Regulation, Gregory Malnassy Jan 2022

Abl2 Promotes Alcohol-Associated Liver Disease Via Ppar Gamma Regulation, Gregory Malnassy

Dissertations

Alcohol-associated liver disease (AALD) is an umbrella term for a spectrum of diseases resulting from chronic alcohol (e.g. ethanol) abuse ranging in severity from reversible conditions such as alcohol-induced steatosis to advanced and largely irreversible liver pathologies including alcoholic steatohepatitis (ASH), alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). AALD is one of the primary causes of chronic liver disease worldwide and accounts for 44% of liver disease deaths in the United States. Drinking rates, both in the United States and globally, have increased year over year for the past three decades, a trend which has resulted in significantly …

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Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah Nov 2021

Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …

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Bridging The 12-6-4 Model And The Fluctuating Charge Model, Pengfei Li Jul 2021

Bridging The 12-6-4 Model And The Fluctuating Charge Model, Pengfei Li

Chemistry: Faculty Publications and Other Works

Metal ions play important roles in various biological systems. Molecular dynamics (MD) using classical force field has become a popular research tool to study biological systems at the atomic level. However, meaningful MD simulations require reliable models and parameters. Previously we showed that the 12-6 Lennard-Jones nonbonded model for ions could not reproduce the experimental hydration free energy (HFE) and ion-oxygen distance (IOD) values simultaneously when ion has a charge of +2 or higher. We discussed that this deficiency arises from the overlook of the ion-induced dipole interaction in the 12-6 model, and this term is proportional to 1/r …

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Somatic Inhibition By Microscopic Magnetic Stimulation, Hui Ye Jun 2021

Somatic Inhibition By Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Electric currents can produce quick, reversible control of neural activity. Externally applied electric currents have been used in inhibiting certain ganglion cells in clinical practices. Via electromagnetic induction, a miniature-sized magnetic coil could provide focal stimulation to the ganglion neurons. Here we report that high-frequency stimulation with the miniature coil could reversibly block ganglion cell activity in marine mollusk Aplysia californica, regardless the firing frequency of the neurons, or concentration of potassium ions around the ganglion neurons. Presence of the ganglion sheath has minimal impact on the inhibitory effects of the coil. The inhibitory effect was local to the …

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Function Of Mllt3 In Liver Metabolism, Grace Ann Hammack Jan 2021

Function Of Mllt3 In Liver Metabolism, Grace Ann Hammack

Master's Theses

The chromatin regulator MLLT3 recognizes target genes through the YEATS domain that identifies post-translationally modified histones, with preference for crotonyl and acetyl marks, and recruits different multiprotein effector complexes through its C-terminal domain to target genes. To study the role of MLLT3 in gene regulation, the Zeleznik-Le and Hemenway labs developed Mllt3 whole-body knockout (Mllt3;Rosa26-CreERT2) mice. These mice have a hematopoietic stem cell phenotype and an unexpected obesity and hepatic steatosis phenotype. It was unknown whether these phenotypes were from liver intrinsic effects or influenced by other parts of the body. To study this fatty liver phenotype further, Mllt3;Alb-Cre were …

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Beta-Adrenergic Receptor Mediated Transcriptional Dysregulation In Hematopoeitc Stem And Progenitor Cells Leads To Bone Marrow Erythroid Suppresion In Multiple Myeloma Patients - Ex Vivo Investigations, Vimal Ravi Subramaniam Jan 2021

Beta-Adrenergic Receptor Mediated Transcriptional Dysregulation In Hematopoeitc Stem And Progenitor Cells Leads To Bone Marrow Erythroid Suppresion In Multiple Myeloma Patients - Ex Vivo Investigations, Vimal Ravi Subramaniam

Master's Theses

The sympathetic nervous system (SNS) regulates our body’s involuntary response to stress or harm. Once activated, it releases hormones and neurotransmitters known as catecholamines throughout the body to mediate its recovery. The catecholamines bind to adrenergic receptors located on various cells in a process designated as adrenergic signaling to elicit this response. This process is not always to our benefit. Adverse symptoms such as anemia can result due to adrenergic signaling. Our laboratory previously showed that burn injury triggers adrenergic receptor stimulation resulting in anemia induced by diminished erythropoiesis. The development of anemia in these studies was found to be …

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Axonal Blockage With Microscopic Magnetic Stimulation, Hui Ye Oct 2020

Axonal Blockage With Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials …

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A Review Of The Preclinical And Clinical Efficacy Of Remdesivir, Hydroxychloroquine, And Lopinavir-Ritonavir Treatments Against Covid-19, Dawid Maciorowski, Samir Z. El Idrissi, Yash Gupta, Brian J. Medernach, Michael B. Burns, Daniel P. Becker Ph.D., Ravi Durvasula, Prakasha Kempaiah Sep 2020

A Review Of The Preclinical And Clinical Efficacy Of Remdesivir, Hydroxychloroquine, And Lopinavir-Ritonavir Treatments Against Covid-19, Dawid Maciorowski, Samir Z. El Idrissi, Yash Gupta, Brian J. Medernach, Michael B. Burns, Daniel P. Becker Ph.D., Ravi Durvasula, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

In December of 2019, an outbreak of a novel coronavirus flared in Wuhan, the capital city of the Hubei Province, China. The pathogen has been identified as a novel enveloped RNA beta-coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus SARS-CoV-2 is associated with a disease characterized by severe atypical pneumonia known as coronavirus 2019 (COVID-19). Typical symptoms of this disease include cough, fever, malaise, shortness of breath, gastrointestinal symptoms, anosmia, and, in severe cases, pneumonia.1 The high-risk group of COVID-19 patients includes people over the age of 60 years as well as people with existing cardiovascular …

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Indoline‐6‐Sulfonamide Inhibitors Of The Bacterial Enzyme Dape, Cory T. Reidl, Tahirah K. Heath, Iman Darwish, Rachel M. Torrez, Maxwell Moore, Elliot Gild, Boguslaw P. Nocek, Anna Starus, Richard C. Holz, Daniel P. Becker Ph.D. Sep 2020

Indoline‐6‐Sulfonamide Inhibitors Of The Bacterial Enzyme Dape, Cory T. Reidl, Tahirah K. Heath, Iman Darwish, Rachel M. Torrez, Maxwell Moore, Elliot Gild, Boguslaw P. Nocek, Anna Starus, Richard C. Holz, Daniel P. Becker Ph.D.

Chemistry: Faculty Publications and Other Works

Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG).

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Phosphorylation Of Adp-Glucose Pyrophosphorylase During Wheat Seeds Development, Danisa M. L. Ferrero, Claudia V. Piattoni, Matías D. Asencion Diez, Bruno E. Rojas, Matías D. Hartman, Miguel A. Ballicora, Alberto A. Iglesias Jul 2020

Phosphorylation Of Adp-Glucose Pyrophosphorylase During Wheat Seeds Development, Danisa M. L. Ferrero, Claudia V. Piattoni, Matías D. Asencion Diez, Bruno E. Rojas, Matías D. Hartman, Miguel A. Ballicora, Alberto A. Iglesias

Chemistry: Faculty Publications and Other Works

Starch is the dominant reserve polysaccharide accumulated in the seed of grasses (like wheat). It is the most common carbohydrate in the human diet and a material applied to the bioplastics and biofuels industry. Hence, the complete understanding of starch metabolism is critical to design rational strategies to improve its allocation in plant reserve tissues. ADP-glucose pyrophosphorylase (ADP-Glc PPase) catalyzes the key (regulated) step in the synthetic starch pathway. The enzyme comprises a small (S) and a large (L) subunit forming an S2L2 heterotetramer, which is allosterically regulated by orthophosphate, fructose-6P, and 3P-glycerate. ADP-Glc PPase was found in a phosphorylated …

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Synthesis Of A Protected 2-Aminocyclobutanone As A Modular Transition State Synthon For Medicinal Chemistry, Thahani S. Habeeb Mohammad, Cory T. Reidl, Matthias Zeller, Daniel P. Becker Ph.D. Mar 2020

Synthesis Of A Protected 2-Aminocyclobutanone As A Modular Transition State Synthon For Medicinal Chemistry, Thahani S. Habeeb Mohammad, Cory T. Reidl, Matthias Zeller, Daniel P. Becker Ph.D.

Chemistry: Faculty Publications and Other Works

The hydrochloride salt of ɑ-aminocyclobutanone protected as its dimethyl acetal 2,2-dimethoxycyclobutan-1-aminium chloride (3) has been prepared as a modular synthon for convenient access to cyclobutanone-containing lead inhibitors of hydrolase enzymes including serine proteases and metalloproteases. Protected ɑ-aminocyclobutanone 3 was converted to representative amide and sulfonamide-functionalized 2-aminocyclobutanone derivatives. Reaction of the amino acetal 3 with phenyl isothiocyanate afforded the bicyclic urea 1-hydroxyl-2,4-diazabicyclo[3.2.0]heptane-3-thione (9) as confirmed by a single crystal X-ray structure.

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Selectivity For Allosteric Effectors Of Bacterial Adp-Glucose Pyrophosphorylase: Structural And Functional Studies, Mashael Alghamdi Jan 2020

Selectivity For Allosteric Effectors Of Bacterial Adp-Glucose Pyrophosphorylase: Structural And Functional Studies, Mashael Alghamdi

Dissertations

The biosynthesis of the intracellular polysaccharide in bacteria and plants, glycogen and starch, respectively, controlled by the key regulatory step that catalyzed by ADP-Glucose Pyrophosphorylase (ADP-Glc PPase). ADP-Glc PPase is an allosteric enzyme regulated by metabolites produced of the principle carbon assimilation pathway in each organism. Agrobacterium tumefaciens enzyme activated by fructose 6-phosphate (Fru6P) and pyruvate, whereas Escherichia coli enzyme activated by fructose 1,6-bisphosphate (FBP), and both enzymes inhibited by AMP. Here, we targeted the allosteric regulation of the A. tumefaciens enzyme, examined some residues that may impact the regulation mechanism (Ser72, His71, Arg75, Ser351, Ser334, Arg368, Asn350, and Asp291), …

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Human Isocitrate Dehydrogenase Enzymes, Joseph Valentein Roman Jan 2020

Human Isocitrate Dehydrogenase Enzymes, Joseph Valentein Roman

Dissertations

Mammals have three forms of isocitrate dehydrogenase (ICDH) that each catalyze the oxidative decarboxylation of isocitrate forming alpha-ketoglutarate (AKG), carbon dioxide and reduced pyridine nucleotide. The intra-mitochondrial, citric acid cycle enzyme is ICDH III that exists as a hetero tetramer and uses NAD+ as a substrate. ICDH I and ICDH II are both dimeric enzymes that reside in the cytosol and use NADP+. While, the precise function of the cytosolic ICDHs is not known, active site variants of both ICDH I and II cause a variety of cancers. The R132H variant of ICDH1 is one of the most common alterations. …

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Laser Surface Cleaning As A Novel Approach For Genesis Solar Wind Collectors, Martina Schmeling, I. V. Veryovkin, C. E. Tripa Jan 2020

Laser Surface Cleaning As A Novel Approach For Genesis Solar Wind Collectors, Martina Schmeling, I. V. Veryovkin, C. E. Tripa

Chemistry: Faculty Publications and Other Works

A new surface cleaning method utilizing lasers has been evaluated for its suitability to Genesis solar wind collectors

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Total Reflection X-Ray Fluorescence, Martina Schmeling Mar 2019

Total Reflection X-Ray Fluorescence, Martina Schmeling

Chemistry: Faculty Publications and Other Works

Total reflection X-ray fluorescence (TXRF) spectrometry is a non-destructive and surface sensitive multi-element analytical method based on energy dispersive X-ray fluorescence spectrometry with detection limits in the lower picogram range. It utilizes the total reflection of the primary X-ray beam at or below the critical angle of incidence. At this angle, the fluorescence intensity is substantially enhanced for samples present as small granular residue or as thin homogenous layer deposited at the surface of a thick substrate. Generally, two types of application exist: micro- and trace-analysis as well as surface and thin-layer analysis. For micro- and traceanalysis, a small amount …

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Mllt3 Regulates Expression Of Genes Critical To Liver Metabolic Homeostasis, Jonathan Richard Dixit Jan 2019

Mllt3 Regulates Expression Of Genes Critical To Liver Metabolic Homeostasis, Jonathan Richard Dixit

Master's Theses

Hepatic steatosis (fatty liver) is increasingly prevalent in the US, and is characterized by triglyceride accumulation within hepatocytes. This is a direct result of an imbalance between lipid import, export, de novo lipogenesis, and beta oxidation. Hepatic steatosis can also progress to nonalcoholic steatohepatitis (NASH) which is characterized by increased hepatocyte damage, inflammation, and fibrosis. Further progression can lead to liver failure or hepatocellular carcinoma, requiring liver transplant or causing death. Our lab recently created Mllt3 conditional whole body knockout mice. These mice developed hepatic steatosis and NASH following Mllt3 deletion. MLLT3 is a master gene regulator that is part …

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Yczr, A New Case Of Plp-Dependent Mocr/Gabr Type Transcription Regulator In Klebsiella Pneumonia, Yuanzhang Zheng Jan 2019

Yczr, A New Case Of Plp-Dependent Mocr/Gabr Type Transcription Regulator In Klebsiella Pneumonia, Yuanzhang Zheng

Dissertations

Increasing number of genes encoding PLP-dependent transcription regulators, MocR/GabR type regulators, have been identified in various bacterial genomes. However, only a handful of them, including MocR, PdxR and GabR have been studied experimentally. They control different aspects of the bacterial metabolism. Only GabR has reported crystallographic structures. MocR/GabR regulators possess a chimeric structure consisted of a WHTH DNA binding domain and an Aminotransferase-like regulation domain, which can bind PLP as an effector in transcription regulation. Such a chimeric construct presents an interesting case in molecular evolution. The regulation domains of All MocR/GabR type regulators loss their catalytic capacity during evolution …

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Characterization Of The Effects Of Sex And Estrogen Receptor Signaling On Antigen-Specific T Cells For Immunotherapy, Flor Cecilia Navarro Negredo Jan 2019

Characterization Of The Effects Of Sex And Estrogen Receptor Signaling On Antigen-Specific T Cells For Immunotherapy, Flor Cecilia Navarro Negredo

Dissertations

Adoptive cell transfer (ACT) immunotherapy using antigen (Ag)-specific T cells is partially effective treating several malignancies but numerous challenges remain in order to improve its therapeutic potential. The roles of host factors, such as sex hormone receptor signaling, that can affect the T cell anti-tumor function remain understudied. The work performed in this dissertation characterized the role of estrogen signaling on T cell function in vitro, and during ACT immunotherapy against hepatocellular carcinoma (HCC) in vivo. Estrogen signaling through ERa enhanced the expression and secretion of Type I effector cytokines including IFNg, TNFa, and Granzyme B in male and female …

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Heteroleptic Nickel Complexes Of A Bulky Bis(Carbene)Borate Ligand, Jorge L. Martinez, Wei-Tsung Less, Maren Pink, Chun-Hsing Chen, Jeremy M. Smith Dec 2018

Heteroleptic Nickel Complexes Of A Bulky Bis(Carbene)Borate Ligand, Jorge L. Martinez, Wei-Tsung Less, Maren Pink, Chun-Hsing Chen, Jeremy M. Smith

Chemistry: Faculty Publications and Other Works

Bis(carbene)borate ligand transfer to the nickel nitrosyl synthon Ni(NO)(PPh3)2Br provides the new nickel nitrosyl complex Ph2B(t BuIm)2Ni(NO)(PPh3). The solid state structure reveals a trigonal pyramidal nickel ion with a very long bond to the apical PPh3 ligand. The complex reversibly dissociates PPh3 in solution to afford three‐coordinate Ph2B(t BuIm)2Ni(NO), with NMR data providing evidence for PPh3 binding at low temperatures. Ligand transfer to Ni(PMe3)2Cl2 provides the square planar complex, Ph2B(t BuIm)2Ni(PMe3)Cl, which shows no evidence for rearranging to the form a homoleptic complex with two bis(carbene)borate ligands. This complex is a suitable synthon for the [Ph2B(t BuIm)2Ni]+ fragment, as demonstrated …

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A Gcn5-Related N-Acetyltransferase (Gnat) Capable Of Acetylating Polymyxin B And Colistin Antibiotics In Vitro, Mateusz P. Czub, Brian Zhang, M. Paul Chiarelli, Karolina A. Majorek, Layton Joe, Pryemyslaw J. Prebski, Alina Revilla, Weiming Wu, Daniel P. Becker, Wladek Minor, Misty L. Kuhn Nov 2018

A Gcn5-Related N-Acetyltransferase (Gnat) Capable Of Acetylating Polymyxin B And Colistin Antibiotics In Vitro, Mateusz P. Czub, Brian Zhang, M. Paul Chiarelli, Karolina A. Majorek, Layton Joe, Pryemyslaw J. Prebski, Alina Revilla, Weiming Wu, Daniel P. Becker, Wladek Minor, Misty L. Kuhn

Chemistry: Faculty Publications and Other Works

Deeper exploration of uncharacterized Gcn5-related N-acetyltransferases has the potential to expand our knowledge of the types of molecules that can be acylated by this important superfamily of enzymes and may offer new opportunities for biotechnological applications. While determining native or biologically relevant in vivo functions of uncharacterized proteins is ideal, their alternative or promiscuous in vitro capabilities provide insight into key active site interactions. Additionally, this knowledge can be exploited to selectively modify complex molecules and reduce byproducts when synthetic routes become challenging. During our exploration of uncharacterized Gcn5-related N-acetyltransferases from Pseudomonas aeruginosa, we identified such an …

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