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Doctoral Dissertations

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Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov Nov 2023

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …


Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker Apr 2023

Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker

Doctoral Dissertations

Cigarette Smoke is a significant cause of morbidity and mortality in the United States, accounting for over 480,000 annual deaths. Of these deaths, the most common cause of mortality in chronic smokers is cardiometabolic diseases. Likewise, a significant portion of smokers experience some form of cardiac, vascular, or metabolic dysfunction throughout their lifetime. More specifically, smoking is shown to induce mitochondrial dysfunction in these tissues, causing an increase in oxidative damage and poor overall health. However, despite the advances in the health outcomes related to cigarette smoke exposure, the mechanisms underlying mitochondrial dysfunction in striated muscle and the vasculature remain …


Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan Oct 2022

Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan

Doctoral Dissertations

Biomaterials are widely applied for the diagnosis and treatment of numerous diseases. In addition to fulfilling specific biological functions, biomaterials must also be non-toxic, biocompatible, and sterilizable to be regarded as safe-for-use. Polymers are excellent candidates for fabricating functional biomaterials due to their wide availability and varied properties and may be natural or synthetic. Polymer precursors are fabricated into coatings, foams, scaffolds, gels, composites, and nanomaterials for several biomedical applications. This dissertation focuses on two types of polymeric biomaterials – protein-based materials and synthetic polymeric nanoparticles. Proteins are biopolymers that naturally occur with a variety of structural and functional properties. …


Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward Sep 2022

Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward

Doctoral Dissertations

Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …


Polymer-Based Strategies For Therapeutic Delivery To Bacterial Biofilms, Cheng-Hsuan Li Oct 2021

Polymer-Based Strategies For Therapeutic Delivery To Bacterial Biofilms, Cheng-Hsuan Li

Doctoral Dissertations

Bacterial infections are emerging threat to public health. Antibiotics once provided front-line treatments to bacterial infections; however, bacteria adapted to resist antibiotics through drug resistance mechanisms and biofilm formation. In this dissertation, I describe polymer-based strategies for therapeutic delivery as treatments of bacterial biofilm infections. Initially, I developed a functional polymer for delivering hydrophobic carvacrol (the primary constituent of oregano oil) to the bacterial biofilms. This strategy incorporates a cross-linking strategy to fabricate a robust yet biodegradable nanoemulsion, improving antimicrobial activity of carvacrol and overcoming antimicrobial resistance development. Next, I demonstrated that this functional polymer-based emulsion platform provides a general …


Using The Suprachiasmatic Nucleus As A Model System To Assess Tolerance And Withdrawal To Alcohol, Jonathan Houghton Lindsay Aug 2017

Using The Suprachiasmatic Nucleus As A Model System To Assess Tolerance And Withdrawal To Alcohol, Jonathan Houghton Lindsay

Doctoral Dissertations

Alcohol abuse induces many disorders including depression, metabolic syndrome, and sleep disturbances. The strong link between alcohol abuse and sleep problems, along with the close connection between sleep and circadian rhythms, led us to investigate ethanol’s effects on the circadian clock. Previous work has shown that acute ethanol blocks photic phase shifts in vivo and glutamatergic phase shifts in vitro. However, neural systems become tolerant to ethanol across different timeframes. Despite both ethanol tolerance and ethanol withdrawal syndrome being listed as criteria for developing alcohol use disorders, little is known about how ethanol tolerance and withdrawal induced hyperexcitability develop and …


Dried Whole Plant Artemisia Annua As A Novel Antimalarial Therapy, Mostafa A. Elfawal Nov 2014

Dried Whole Plant Artemisia Annua As A Novel Antimalarial Therapy, Mostafa A. Elfawal

Doctoral Dissertations

Dried Whole plant Artemisia annua as a novel antimalarial therapy September 2014 Mostafa Ahmed Elfawal Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Stephen M. Rich Malaria is one of the worst vector-borne parasitic diseases in the developing world. The World Health Organization (WHO) estimated that 215 million cases of malaria occurred, with >655,000 deaths; half the world’s population is at risk of contracting the disease. Drugs are primary weapons for reducing malaria in human populations. Successful drugs are highly efficacious and inexpensive to manufacture synthetically. However, emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that …


“Effects Of N-3 And N-6 Polyunsaturated Fatty Acids On Human Promyelocytic Hl- 60 Cells, Robert Clements Gillis Aug 2003

“Effects Of N-3 And N-6 Polyunsaturated Fatty Acids On Human Promyelocytic Hl- 60 Cells, Robert Clements Gillis

Doctoral Dissertations

Enteral nutrition with eicosapentaenoic acid (EPA; 20:5 n-3) and γ-linolenic acid (GLA; 18:3 n-6) decreased pulmonary inflammation by reducing neutrophil counts and chemotactic factors in bronchoalveolar lavage fluid during acute respiratory distress syndrome (ARDS). We hypothesize that the antiinflammatory effects of EPA and GLA may be due, in part, to induction of neutrophil apoptosis. Neutrophil apoptosis is an important physiological process in the resolution of pulmonary inflammation. Furthermore, pro-inflammatory eicosanoids formed from arachidonic acid (AA) by lipoxygenase (LO) and cyclooxygenase (COX) pathways have been shown to inhibit apoptosis in certain cell types. The purpose of this dissertation is to determine …