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Articles 1 - 30 of 33
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Computationally Modeling Dynamic Biological Systems, Katherine Jarvis
Computationally Modeling Dynamic Biological Systems, Katherine Jarvis
Electronic Theses and Dissertations
Modeling biological systems furthers our understanding of dynamic relationships and helps us make predictions of the unknown properties of the system. The simple interplay between individual species in a dynamic environment over time can be modeled by equation-based modeling or agent- based modeling (ABM). Equation based modeling describes the change in species quantity using ordinary differential equations (ODE) and is dependent on the quantity of other species in the system as well as a predetermined rates of change. Unfortunately, this method of modeling does not model each individual agent in each species over time so individual dynamics are assumed to …
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge
Electronic Theses and Dissertations
It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam
Impact Of Pank1 Deletion On Mitochondrial Acetylation And Cardiac Function During Pressure Overload., Timothy N. Audam
Electronic Theses and Dissertations
Recent studies have associated elevated protein acetylation levels with heart failure in humans. Although mechanisms promoting elevated acetylation levels are not fully known, excess acetyl-CoA may drive enzyme-independent acetylation of cardiac proteins. Accumulation of acetyl-CoA depends on the availability of sufficient CoA, whose production is regulated by pantothenate kinases in the CoA biosynthetic pathway. We show that cardiac proteins are hyperacetylated during heart failure in humans and tested in mice whether limiting CoA abundance would improve ventricular remodeling during pressure overload-induced hypertrophy. We limited cardiac CoA levels by deleting the rate-limiting enzyme in CoA biosynthesis, Pank1 (one of three PANK-encoding …
The Intersection Of Extracellular Signaling And Stress Pathways, Sari Mayhue
The Intersection Of Extracellular Signaling And Stress Pathways, Sari Mayhue
Electronic Theses and Dissertations
Cell growth is reliant on the flawless orchestration of cellular signaling and is crucial to evade cancer metastasis. It is important to understand key elements of cellular processes like gene regulation and stress signaling and how they contribute to oncogenesis. Cancer cells prove exceptionally adaptive as they effectively evade cellular stress, thus encouraging a tumor hospitable environment and subsequently cancer metastasis. Protein-folding and cellular homeostasis are essential functions of the endoplasmic reticulum (ER). An overabundance of protein accumulation within the ER jeopardizes cellular homeostasis causing stress. Under ER stress, these functions fail to maintain cellular stability resulting in the activation …
Lipidomic Analysis Of Various Developmental Stages Of Physcomitrium Patens, Deepshila Gautam
Lipidomic Analysis Of Various Developmental Stages Of Physcomitrium Patens, Deepshila Gautam
Electronic Theses and Dissertations
Lipids maintain fluidity of the cell membrane during the lifetime of all organisms. The moss Physcomitrium patens, an early land plant, enters reproductive phase under cold (15°C) conditions relative to its gametophytes (22°C). Thus, we hypothesized that their lipid content and composition would be distinct. Using ESI-MS/MS, we showed that the content and acyl composition of 11 lipid classes varied during development. Galactolipids were abundant in gametophytes but insignificant in sporophytes; among phospholipids, phosphatidylcholine was predominant in both phases. Although, sporophytes contained around five-fold less lipids than the gametophyte, their phosphatidic acid content, which accumulates during stress, was 18-fold …
Computational And Biochemical Characterizations Of Anhydrobiosis-Related Intrinsically Disordered Proteins., Brett R. Janis
Computational And Biochemical Characterizations Of Anhydrobiosis-Related Intrinsically Disordered Proteins., Brett R. Janis
Electronic Theses and Dissertations
Anhydrobiosis is the remarkable phenomenon of “life without water”. It is a common technique found in plant seeds, and a rare technique utilized by some animals to temporarily stop the clock of life and enter a stasis for up to several millennia by removing all of their cellular water. If this phenomenon can be replicated, then biological and medical materials could be stored at ambient temperatures for centuries, which would address research challenges as well as enhance the availability of medicine in areas of the world where refrigeration, freezing, and cold-chain infrastructure are not developed or infeasible. Furthermore, modifying crop …
Regulation Of The Ribosome Biogenesis Factor Hyvh1 By Src-Mediated Phosphorylation, Ashley Anne Dadalt
Regulation Of The Ribosome Biogenesis Factor Hyvh1 By Src-Mediated Phosphorylation, Ashley Anne Dadalt
Electronic Theses and Dissertations
The protein tyrosine phosphatase (PTP) superfamily is a major segment of the signal transduction landscape, responsible for regulating the biomolecular phosphorylation status of the cell. Diverse PTP subclasses exist, some of which are understudied and whose cellular functions are not yet fully elucidated. YVH1, an atypical PTP of the dual-specificity phosphatase (DUSP) subclass, is a pleiotropic enzyme with no known substrate. Human YVH1 (hYVH1) protects cells from cellular stressors, including heat shock and oxidative stress, regulates the cell cycle, disassembles stress granules, and acts as 60S ribosome biogenesis factor. Additionally, heat shock protein 70 (Hsp70) has been found to be …
Hla Blockers For Potentially Treating Rheumatoid Arthritis, Samaneh Mehri
Hla Blockers For Potentially Treating Rheumatoid Arthritis, Samaneh Mehri
Electronic Theses and Dissertations
Autoimmune diseases occurs when the immune system recognize self antigens in the body as foreign invaders leads to dysfunction of tissue. RA is an autoimmune disease, caused by improper recognition of self-peptides, particularly human cartilage glycoprotein and type II collagen, by specific human leukocyte antigen (HLA) receptors. Normally T-cell specific for these peptides are destroyed in the thymus before they are released, preventing autoimmunity. However, certain post-translational modifications, especially citrullination, can lead to “self-peptide” recognition by non-self T cells: in the case of RA, one HLA protein (DRB*0401), out of about 1700 possible ones, is responsible for 65% of RA …
Identification Of Fluoxetine-Sert Interactions And Apo-Sert Studies Via Crosslinking Mass Spectrometry, Elizabeth Castellano
Identification Of Fluoxetine-Sert Interactions And Apo-Sert Studies Via Crosslinking Mass Spectrometry, Elizabeth Castellano
Electronic Theses and Dissertations
The serotonin transporter (SERT) is a member of the neurotransmitter sodium symporter family of transporters. SERT controls the magnitude and duration of serotonergic neurotransmission by facilitating the reuptake of serotonin back into the pre-synaptic neuron and is thus a target for antidepressants. Selective serotonin re-uptake inhibitors (SSRIs) such as fluoxetine, are commonly prescribed to treat depression. SSRIs act by blocking reuptake and prolonging serotonin signaling. However, significant problems regarding selectivity and mechanisms of action of these drugs remain unresolved. The structures of SERT and related transporters have been determined and serve as useful structural models. However, they are typically mutated …
Hydrodynamic Characteristics Of The Shortfin Mako Shark (Isurus Oxyrinchus) For Two Caudal Fin Morphologies, Matthew C. Rodriguez
Hydrodynamic Characteristics Of The Shortfin Mako Shark (Isurus Oxyrinchus) For Two Caudal Fin Morphologies, Matthew C. Rodriguez
Electronic Theses and Dissertations
No abstract provided.
Investigations Of Elastin Recoil On Molecular And Macroscopic Levels., Nour Mohammad Jamhawi
Investigations Of Elastin Recoil On Molecular And Macroscopic Levels., Nour Mohammad Jamhawi
Electronic Theses and Dissertations
Elastin is one of the most hydrophobic proteins, and it is extremely flexible when hydrated. The driving force for recoil is the decrease in entropy of the protein and/or the hydrating solvent. This dissertation is a study of both mechanisms. Following an introduction (Chapter 1), Chapters 2 and 3 investigate the recoil mechanism on the molecular level in the hydrating solvent and in the protein, respectively. Chapter 4 examines macroscopic properties of recoil by thermomechanics. Conclusions are discussed in Chapter 5. Using double quantum NMR, the deuterated water ordering at the elastin surface was studied quantitatively as a function of …
Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek
Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek
Electronic Theses and Dissertations
JC polyomavirus (JCPyV) is a human-specific pathogen that infects 50-80% of the population, and can cause a deadly, demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). In most of the population, JCPyV persistently infects the kidneys but during immunosuppression, it can reactivate and spread to the central nervous system (CNS), causing PML. In the CNS, JCPyV targets two cell types, astrocytes, and oligodendrocytes. Due to the hallmark pathology of oligodendrocyte lysis observed in disease, oligodendrocytes were thought to be the main cell type involved during JCPyV infection. However, recent evidence suggests that astrocytes are targeted by the virus and act …
Molecular Dynamics Simulations Provide Insight Into Stability Of Hyperthermophilic Endoglucanases, Logan E. Sheffield
Molecular Dynamics Simulations Provide Insight Into Stability Of Hyperthermophilic Endoglucanases, Logan E. Sheffield
Electronic Theses and Dissertations
Endoglucanases play a key role in the industrial production of bioethanol, but the most efficient method requires the utilization of high temperatures and is currently limited by the thermostability of endoglucanases. For this reason, it would be beneficial to discover more high-efficiency, thermostable enzymes to utilize in the hydrolytic process. In this study molecular dynamics simulations were performed on structurally similar endoglucanases with varying levels of thermostability to gain insight on what factors contribute to thermostability in endoglucanases. RMSD, RMSF, PCA, hydrogen bonding and salt bridges were analyzed. Finally, protein energy networks were constructed from nonbonded interaction potentials and analysis …
Hells And Prdm9 Form A Pioneer Complex To Open Chromatin At Meiotic Recombination Hotspots: A Technological Perspective, Catrina Spruce
Hells And Prdm9 Form A Pioneer Complex To Open Chromatin At Meiotic Recombination Hotspots: A Technological Perspective, Catrina Spruce
Electronic Theses and Dissertations
Chromatin functions as a physical barrier regulating access to DNA, however pioneer factors are able to engage partial recognition motifs present within nucleosomal DNA to initiate access to specific DNA sequences. During spermatogenesis, genomic locations that become recombination hotspots are generally in regions of closed chromatin, or heterochromatin, before meiosis. However, in leptotene and zygotene stages of meiosis, PRDM9 marks nucleosomes at recombination hotspots with H3K4me3 and H3K36me3 and recruits other factors that deposit additional histone marks. Here I focus on the technological approaches by which we discovered that hotspots also transition from closed to open chromatin, dependent on the …
Characterizing The Dormancy And Repair Of A Circumneutral Passive Remediation System Receiving Iron And Sulfate-Rich Amd, Garrett Struble
Characterizing The Dormancy And Repair Of A Circumneutral Passive Remediation System Receiving Iron And Sulfate-Rich Amd, Garrett Struble
Electronic Theses and Dissertations
The Wingfield Pines remediation system is a ~20-acre circumneutral, gravity-fed system constructed in 2009 to passively remediate Fe from an ~2000 gallon/minute effluent. In 2017, a fracture to the system’s underground cavern caused the AMD effluent to bypass the system, flowing directly into Chartiers Creek and leaving the system decommissioned between 2017-2019. Soil slurry and water samples were collected in the weeks prior to the system’s reinstalment in September 2019 through January 2020 in order to determine the effect of the repair on remediation efficiency and microbial community composition. This study acted as the first to describe the temporary decommissioning …
Rna G-Quadruplex Structures: Functions In Noncoding Rnas And Disease, Emily Benner
Rna G-Quadruplex Structures: Functions In Noncoding Rnas And Disease, Emily Benner
Electronic Theses and Dissertations
Paraspeckles are a relatively newly identified subnuclear body whose function is still largely unknown. They are membraneless organelles found within mammalian nuclei originally identified as being comprised of different paraspeckle proteins (PSPs), and later proven to also contain RNA. This study investigates the long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1), which has been found to be indispensable in the formation of paraspeckles, with each containing up to 50 NEAT1 molecules. NEAT1 has two isoforms, the shorter NEAT1_1, and the longer NEAT1_2. The focus of this work will be on the NEAT1_2, which acts as a scaffold in the …
Simulation Of The Interaction Between Striated Muscle Unc-45 And Transcription Factor Gata-4, Drake Alexander Duncan
Simulation Of The Interaction Between Striated Muscle Unc-45 And Transcription Factor Gata-4, Drake Alexander Duncan
Electronic Theses and Dissertations
Striated Muscle UNC-45, also known as UNC-45b, is an important protein that acts as a chaperone for myosin in cardiac and skeletal muscles, binding to myosin at its C-terminal UCS domain and regulating its assembly into thick filaments and sarcomeric structures. The UCS domain contains a large loop that is believed to be the first point of interaction between myosin and UNC-45b. GATA-4 is an essential transcription factor that facilitates transcription of several genes in cardiac development, particularly alpha-heavy chain myosin in heart tissue. Recently, studies have shown that there is interaction of GATA-4 with UNC-45b and that GATA-4 binds …
Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit
Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit
Electronic Theses and Dissertations
Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second enzymatic step within the serine synthetic pathway (SSP) and its expression is elevated in numerous human cancers, including non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutant NSCLC is characterized by activating mutations within its tyrosine kinase domain and accounts for 17% of lung adenocarcinomas. Although elevated SSP activity has been observed in EGFR-mutant lung cancer cells, the involvement of PSAT1 in EGFR-mediated oncogenesis is still unclear. Here, we explore a putative non-canonical function for PSAT1 using biochemical approaches to elucidate unknown interacting proteins and genomic RNA-seq profiling to identify cellular …
Characterization Of Cucurbitacin-Inspired Estrone Analogues As Novel Inhibitors Of Human Atp- Binding Cassette Proteins (Abcb1 And Abcc1), Jennifer Kyeremateng
Characterization Of Cucurbitacin-Inspired Estrone Analogues As Novel Inhibitors Of Human Atp- Binding Cassette Proteins (Abcb1 And Abcc1), Jennifer Kyeremateng
Electronic Theses and Dissertations
ATP-binding cassette (ABC) transporters are a large class of integral membrane proteins that contribute to key physiological functions in all organisms by utilizing ATP binding and hydrolysis to transport diverse substrates across membrane barriers. P-glycoprotein (P-gp/ ABCB1) and Multidrug Resistance protein 1 (MRP1/ABCC1) are widely reported ABC transporters associated with multidrug resistance in cancer. Multidrug resistance (MDR) mediated by P-gp and MRP1 is responsible for treatment failures of many metastatic cancers as a result of reduced accumulation, bioavailability and diminished potency of anticancer drugs. Currently, known P-gp and MRP1 inhibitors are limited due to toxicity, lack of selectivity and low …
Therapeutic Immunoglobulin G Surface Mobility Promotes Antibody-Dependent Cellular Phagocytosis By Arp2/3 And Syk Mediated Rearrangement Of Fcγ Receptors, Seongwan Jo
Electronic Theses and Dissertations
Therapeutic antibodies are rapidly growing class of drugs for treating cancers and immunological disorders by targeting specific antigens or blocking certain pathway to inhibit the tumor growth. In cancer immunotherapy, it was found that Fcγ receptor (FcγR) in immune cells play an important role in antibody dependent cell toxicity against tumor cells. Therefore, understanding FcγR activation mechanism, which requires ligation with immunoglobulin (IgG), is crucial to enhance potency of therapeutic antibodies. One crucial immune responses triggered upon FcγR ligation with IgG is phagocytosis which indicates clearing targets by engulfment. It is known that FcγRs form microclusters which gets rearranged during …
Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns
Optimized Microbial Recombinant Production Of Hiv-1 Anti-Envelope Antibody Fragments With Applications To Single Particle Tracking Of Virus Assembly, Merissa Michelle Bruns
Electronic Theses and Dissertations
In my findings, I have established a set series of protocols to recombinantly produce, purify and apply various fluorescent probes in vitro for the fluorescent labeling and study of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein during HIV viral assembly. There remains insufficient knowledge about the molecular dynamics and interactions of HIV-1 Env protein with its counterpart, Gag, on the inner host cell surface during assembly of a mature virus particle. There also remains an insufficient amount of data for the understanding and clarification of the mechanism of action of a known host cell HIV-1 restriction factor, …
Rab35 Centered Membrane Trafficking Pathway Directs Apical Constriction During Drosophila Gastrulation, Hui Miao
Electronic Theses and Dissertations
Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating high-tension contractile forces at the cell cortex before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be cellular processes to extract unidirectional changes that drive processive transformations in cell shape. During Drosophila melanogastergastrulation, the invagination of the prospective mesoderm is driven by the pulsed constriction of apical surfaces. Here, we address the mechanisms by which the irreversibility of pulsed events is achieved while also permitting uniform epithelial behaviors to emerge. We use MSD-based analyses to identify contractile steps and find that when a …
Validation Of A Deployable Proteomic Assay For The Serological Screening Of Sexual Assault Samples, Catherine O'Sullivan Brown
Validation Of A Deployable Proteomic Assay For The Serological Screening Of Sexual Assault Samples, Catherine O'Sullivan Brown
Electronic Theses and Dissertations
Protein mass spectrometry (MS) has emerged as a technique to supplant traditional serological tests for body fluid identification. It was hypothesized that proteomic techniques would surpass the sensitivity and specificity of traditional serological techniques. An automated workflow coupled with protein MS has been developed for the confirmatory identification of five biological fluids. A developmental validation was completed, assessing parameters such as reproducibility, sensitivity, ion suppression, and limit of detection. Implementation was determined through tandem sample processing by MS, traditional serological tests, and standard DNA profiling methods. The MS approach offered superior detection limits while also providing true confirmatory results, producing …
Nucleic Acids Promote Oligomerization Of Immunoglobulin G, Alexa Gomez
Nucleic Acids Promote Oligomerization Of Immunoglobulin G, Alexa Gomez
Electronic Theses and Dissertations
Nucleic acids have been found to prevent aggregation as chaperones, as well as act as co-factors and promote aggregation of amyloidogenic proteins leading to various diseases. Immunoglobulin G, IgG, are prone to aggregate as therapeutic proteins, and light chains of IgG can form amyloid fibrils, causing a disease known as light chain amyloidosis. Here we discuss the effect nucleic acids have on full-length immunoglobulin G aggregation. Our results show G-quadruplex DNA, and bulk DNA lead to oligomerization of full-length IgG, and induce increases in secondary structure. Tryptophan fluorescence indicates structural changes are occurring in the presence of DNA. Additionally, IgG …
Modeling Disorder In Proteins Yields Insights Into The Evolution Of Stability And Function, Jonathan Huihui
Modeling Disorder In Proteins Yields Insights Into The Evolution Of Stability And Function, Jonathan Huihui
Electronic Theses and Dissertations
The central dogma of molecular biology dictates that a DNA sequence codes for an RNA sequence, which in turn codes for a sequence of amino acids that comprises a protein. Proteins are responsible with performing myriad functions within living organisms and most proteins require a folded structure in order to perform their function. The protein's structure is the direct link from sequence to function. This is known as the sequence - structure - function paradigm. However, this does not mean that the unfolded state is unimportant. In order to properly model the stability of the folded state, one needs to …
Characterization Of The Whale Shark (Rhincodon Typus) Melanocortin-2 Receptor, Brianne Hoglin
Characterization Of The Whale Shark (Rhincodon Typus) Melanocortin-2 Receptor, Brianne Hoglin
Electronic Theses and Dissertations
Among bony vertebrates, the melanocortin-2 receptor ortholog is unique among the family of five melanocortin receptors on the basis that it is dependent on its accessory protein, MRAP1, for trafficking and activation, and is selective for activation by ACTH alone. Previous studies on the MC2R orthologs of select cartilaginous fish, the elephant shark (Callorhinchus milii) and the red stingray (Dasyatis akajei), revealed divergent traits in a less obligatory relationship on MRAP1 and its ability to be activated by ACTH or the MSH-sized peptides. However, observed traits were not consistent between these two cartilaginous fish species, posing …
Development Of Endoplasmic Reticulum Targeted Probes And Red Fluorescent Probes For Detecting Zinc, Drew Maslar
Development Of Endoplasmic Reticulum Targeted Probes And Red Fluorescent Probes For Detecting Zinc, Drew Maslar
Electronic Theses and Dissertations
Zinc (Zn2+) is the second most abundant transition metal in the body and is important in various biological functions. Fluorescent sensors based on circularly permuted fluorescent proteins (cpFPs) have been previously made to detect labile, or unbound, Zn2+ within the cytoplasm of cells. These sensors have proven invaluable for studying Zn2+, however, these sensors are limited to their use in the cytoplasm and by the fact that only green cpFP have been utilized to create fluorescent Zn2+ sensors. In this thesis, we use a combination of peptide targeting sequences, site-directed mutagenesis, and rational design …
Fxs-Causing Point Mutations In Fmrp Disrupt Neuronal Granule Formation And Function, Emily L. Starke
Fxs-Causing Point Mutations In Fmrp Disrupt Neuronal Granule Formation And Function, Emily L. Starke
Electronic Theses and Dissertations
Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by the disruption of Fragile X Mental Retardation Protein (FMRP) function in neurons, affecting nearly 1 in 7,500 individuals. Although FXS typically occurs from a complete loss of FMRP expression due to a CGG trinucleotide expansion within the 5’UTR of the FMR1 gene, single nucleotide polymorphisms (SNPs) within the KH domains of FMRP have been shown to severely disrupt FMRP function. FMRP is an RNA-binding translation repressor that interacts with ~4% of the neuronal transcriptome. Many target mRNAs encode for proteins important for regulating synaptic processes and modulate synaptic plasticity. It …
Study Of Student Resource Use In Introductory Chemistry Courses, Sarah E. Melvin
Study Of Student Resource Use In Introductory Chemistry Courses, Sarah E. Melvin
Electronic Theses and Dissertations
According to the U.S. Government Accountability Office (GAO), college textbook prices have increased by 186% from 1986 to 2004.1 The impact of rising cost of textbooks is increasingly apparent as students are becoming more selective in the courses they enroll in, as well as more concerned with the quality of the learning experience they receive once enrolled in a course.1 In response to high textbook prices, open-education resources (OER) are increasingly becoming more accepted for student use as an alternative to traditional textbook options. OERs are open-source textbook and/or materials that are free to use without worrying about copyright …
Profiling Of Fda-Approved And Clinical Trial Drugs Revealed Shared Cytotoxicity And Collateral Sensitivity In Resistant (H69ar) And Non-Resistant (H69) Small Cell Lung Cancer Cells. (Drug Repurposing In Cancer Chemotherapy), Pius Reyderg Agyemang
Electronic Theses and Dissertations
Some cancers are capable of “spitting out” drugs being fed to them, metaphorically speaking, becoming resistant to what were previously effective chemotherapeutics. In small-cell lung cancer (SCLC), an overexpression of a membrane protein (MRP1) and its transport activity can lead to chemotherapy failure. However, this study showed that certain drugs are selectively cytotoxic (exhibit collateral sensitivity) to MRP1-overexpressed SCLC (H69AR) cells. In this study, three drugs (Erlotinib, Pyrimethamine, Fludarabine) were identified to exhibit a dose-dependent collateral sensitivity on H69AR with IC50 values of ~3.5 μM, ~2 μM, and ~20 μM respectively. Halting the transport activity of the MRP1 with 25 …