Biology Commons^™

Design Of Drug Nano-Carriers For Study Of Multidrug Resistance In Single Live Cells, Pavan Kumar Cherukuri

Chemistry & Biochemistry Theses & Dissertations

Multidrug resistance (MDR) exists in both prokaryotic and eukaryotic cells. MDR is responsible for ineffective treatment of a wide range of diseases, such as infections and cancer. The ATP-binding cassette (ABC) membrane transporters (efflux pumps) are one of the largest and most diverse super-families of membrane proteins found in all living organisms, ranging from bacteria to humans. All ABC transporters share a common structure of four core domains; two transmembrane domains (TMD) with variable sequence and topology and two nucleotide-binding domains (NBD) with conserved sequences. Conventional methods for the study of the efflux functions are radioactively labeled substrates and fluorescent …

Talin2-Mediated Traction Force Drives Matrix Degradation And Cell Invasion, Lei Qi, Naser Jafari, Xiang Li, Zaozao Chen, Liqing Li, Vesa P. Hytönen, Benjamin T. Goult, Chang-Guo Zhan, Cai Huang

Markey Cancer Center Faculty Publications

Talin binds to β-integrin tails to activate integrins, regulating cell migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2, encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion dynamics, cell migration and invasion, whereas the biological function of talin2 is not clear and, indeed, talin2 has been presumed to function redundantly with talin1. Here, we show that talin2 has a much stronger binding to β-integrin tails than talin1. Replacement of talin2 Ser339 with Cys significantly decreased its binding to β1-integrin tails to a level comparable to that of talin1. Talin2 localizes at invadopodia and is indispensable …

Lack Of Interaction Between Erbb2 And Insulin Receptor Substrate Signaling In Breast Cancer, Sarah M. Farabaugh, Bonita T. Chan, Xiaojiang Cui, Robert Dearth, Adrian V. Lee

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

Background: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbBmediated anti-estrogen resistance in breast cancer. Herein, we examined crosstalk between ErbB2 and IRSs using cancer cell lines and transgenic mouse models.

Methods: MMTV-ErbB2 and MMTV-IRS2 transgenic mice were crossed to create hemizygous MMTV-ErbB2/MMTVIRS2 bigenic mice. Signaling crosstalk …

Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang

Biostatistics Faculty Publications

Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to …

Identification Of Pathway-Specific Serum Biomarkers Of Response To Glucocorticoid And Infliximab Treatment In Children With Inflammatory Bowel Disease, Christopher R. Heier, Alyson A. Fiorillo, Ellen Chaisson, Heather A. Gordish-Dressman, Yetrib Hathout, Jesse M. Damsker, Eric P. Hoffman, Laurie S. Conklin

Genomics and Precision Medicine Faculty Publications

Objective:

Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial.

Methods:

We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed …

Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran

Publications and Research

Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …

Exercise To The Rescue: An Analysis Of Altered Metabolic Gene Regulation Post-Exercise In Lean And Obese Individuals, Brandon Mudd

Mahurin Honors College Capstone Experience/Thesis Projects

The skeletal muscle of obese individuals exhibits a depressed ability to metabolize fats. Exercise training is thought to rescue this dampened ability to metabolize fats; mediated by a coordinated increase in the expression of a network of genes that regulate metabolism and fuel utilization. The purpose of this study is to determine the exercise-induced regulation of metabolically important genes in lean and obese individuals. Muscle biopsies (one pre-exercise/baseline and one immediately post-exercise) were obtained from 4 lean (BF% 24.4 ± 5.5; 23.5 yrs ± 1.9) and 13 obese (BF% 39.7 ± 2.4; 26.1 yrs ± 2.3), age-matched, relatively young subjects, …

The Role Of Osteocyte Estrogen Receptor Beta (Erβ) In Regulating The Skeletal Response To Mechanical Loading, Julia P. Townsend, Russell P. Main

The Summer Undergraduate Research Fellowship (SURF) Symposium

Estrogen’s biological functions are mediated by estrogen binding to estrogen receptors (ER). Understanding what role both ERα and ERβ have in bone maintenance and formation can contribute to possible treatment of osteoporosis. This study examined osteocyte specific deletion of ERβ in mice. The cross of ERβ-floxed mice with DMP1-8kb-Cre mice provided both experimental knockout mice as well as littermate control mice. At 24 weeks of age the left tibiae of all mice were mechanically loaded five days per week for two weeks to induce bone formation. Analysis of cortical bone was conducted using microcomputed tomography (microCT) to measure load-induced changes …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

Purinergic Signaling During Porphyromonas Gingivalis Infection, C. Silva, A. C. Morandini, David M. Ojcius, R. Coutinho-Silva,

All Dugoni School of Dentistry Faculty Articles

Despite recent advances unraveling mechanisms of host–pathogen interactions in innate immunity, the participation of purinergic signaling in infection-driven inflammation remains an emerging research field with many unanswered questions. As one of the most-studied oral pathogens, Porphyromonas gingivalis is considered as a keystone pathogen with a central role in development of periodontal disease. This pathogen needs to evade immune-mediated defense mechanisms and tolerate inflammation in order to survive in the host. In this review, we summarize evidence showing that purinergic signaling modulates P. gingivalis survival and cellular immune responses, and discuss the role played by inflammasome activation and cell death during …

Characterization Of The Role Of Host And Dietary Factors In The Establishment Of Bacteria In The Gastrointestinal Tract, Janina A. Krumbeck

School of Biological Sciences: Dissertations, Theses, and Student Research

Probiotic bacteria and synbiotics are used as therapeutic and prophylactic agents. The majority of probiotic and synbiotic applications contain bacterial strains that are allochthonous to the human gastrointestinal (GI) tract. Accordingly, many bacterial strains do not survive digestion, or are not capable of persisting and competing the resident gut microbiota, and are therefore washed out of the GI tract shortly after the treatment is discontinued. This might reduce the health effects of these treatments. Therefore, research is needed to address the ecological challenges that probiotic strains encounter in the GI tract in order to develop probiotic regimens. Determining which ecological …

Induction Of Human Embryonic Stem Cell Derived Retinal Stem Cells In Vitro Using Transient Overexpression Of Messenger Rna For Blimp, Onecut1 And Otx2, Helen Cifuentes

Dissertations, Masters Theses, Capstones, and Culminating Projects

No abstract available

Ciliate Codon Translator Program Manual, Quentin D. Altemose

Mathematics Summer Fellows

Understanding the evolutionary history of organisms allows us to better comprehend selective pressures and their effects on larger populations. In our study, we focused on analyzing the DNA of ciliate groups, which are single celled protozoans characterized by the presence of cilia on their outer membrane. We utilized the DNA of the organisms to analyze the changes in population genotype over time. We tested existing evolutionary models (designed to represent natural genetic variation over time in populations) against our data to identify the model with the best fit and likelihood. From the DNA and the evolutionary model with the highest …

Distinct And Shared Functions Of Als-Associated Proteins Tdp-43, Fus And Taf15 Revealed By Multisystem Analyses, Katannya Kapeli, Gabriel A. Pratt, Anthony Q. Vu, Kasey R. Hutt, Fernando J. Martinez, Balaji Sundararaman, Ranjan Batra, Peter Freese, Nicole J. Lambert, Stephanie C. Huelga, Seung J. Chun, Tiffany Y. Liang, Jeremy Chang, John P. Donohue, Lily Shiue, Jiayu Zhang, Haining Zhu, Franca Cambi, Edward J. Kasarskis, Shawn Hoon, Manuel Ares Jr., Christopher B. Burge, John Ravits, Frank Rigo, Gene W. Yeo

Molecular and Cellular Biochemistry Faculty Publications

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor …

Early-Onset Alzheimer’S: Should You Worry?, Troy Rohn

Biology Faculty Publications and Presentations

You have forgotten where you put your car keys, or you can’t seem to remember the name of your colleague you saw in the grocery store the other day. You fear the worst, that maybe these are signs of Alzheimer’s disease.

Botanical Therapeutics In The Modern World, Vyacheslav Dushenkov, Brittany L. Graf, Mary Ann Lila

Publications and Research

Plants are the source of a broad spectrum of biologically active phytochemicals. For effective defense against pathogens and abiotic stress, plants have developed complicated chemical strategies with different mechanisms of action. By harnessing these phytochemicals, humans have used plants for medicinal purposes for over 30,000 years, and they remain a valuable source for the development of modern therapeutics. Plant-derived materials are utilized as pharmaceuticals, botanical drugs, dietary supplements (nutraceuticals), functional food ingredients, and cosmeceuticals. The Global Institute for Bioexploration (GIBEX), an international conglomerate of researchers, is involved in multiple botanical therapeutics discovery and development programs.

Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang

Genomics and Precision Medicine Faculty Publications

There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary tumor …

Investigating The Origin And Functions Of A Novel Small Rna In Escherichia Coli, Fenil Rashmin Kacharia

Dissertations and Theses

Non-coding small RNAs (sRNAs) regulate various cellular processes in bacteria. They bind to a chaperone protein Hfq for stability and regulate gene expression by base-pairing with target mRNAs. Although the importance of sRNAs in bacteria has been well established, the mode of origination of novel sRNA genes is still elusive, mainly because the rapid rate of evolution of sRNAs obscures their original sources. To overcome this impediment, we identified a recently formed sRNA (EcsR2) in E. coli, and show that it evolved from a degraded bacteriophage gene. Our analyses also revealed that young sRNAs such as EcsR2 are expressed …

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …

Alternative Functions For The Multifarious Inflammasome, J. Martel, H. C. Lai, Y. F. Ko, J. D. Young, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

The inflammasome has been mainly studied in innate immune cells in which it senses microbes and cellular damage, and induces secretion of pro-inflammatory cytokines. This process induces an inflammatory response that is critical for the resolution of infections and repair of tissue damage following injury. Recent studies indicate that inflammasome complex formation also participates in many other cellular and physiological processes beyond modulation of inflammation, such as autophagy, metabolism, eicosanoids production, and phagosome maturation.

Assessment Of Daf-19 Related Behavioral Defects, Loraina A. Stinson

Lawrence University Honors Projects

The daf-19 gene encodes the only RFX transcription factors in C. elegans, producing at least four related protein isoforms, one of which, DAF-19C, is responsible for ciliogenesis. Previous work by Senti and Swoboda (2008) demonstrated that adult worms deficient in all four DAF-19 proteins have extremely aberrant dwelling and roaming behavior on bacterial food. Most intriguingly, the addition of cDNA encoding the DAF-19C isoform restores cilia formation, but does not fully restore wild-type dwelling and roaming behavior. We are suggesting that additional neuron functions are needed to properly execute behaviors and these neuron functions require the activity of other …

Identification And Use Of Indicator Data To Develop Models For Marine-Sourced Risks In Massachusetts Bay, Marin M. Kress

Graduate Doctoral Dissertations

The coastal watersheds around Massachusetts Bay are home to millions of people, many of whom recreate in coastal waters and consume locally harvested shellfish. Epidemiological data on food-borne illness and illnesses associated with recreational water exposure are known to be incomplete. Of major food categories, seafood has the highest recorded rate of associated foodborne illness. In total, the health impacts from these marine-sourced risks are estimated to cost millions of dollars each year in medical expenses or lost productivity. When recorded epidemiological data is incomplete it may be possible to estimate abundance or prevalence of specific pathogens or toxins in …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Phylogenetic Analysis Of Human Cytomegalovirus Pus27 And Pus28: Ascertaining An Independent Or Linked Evolutionary History, Jessica A. Scarborough

Undergraduate Honors Theses

Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skilled at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host’s immune system. One aspect of this co-evolution involves the acquisition of four virally encoded GPCR chemokine receptor homologs, products of the US27, US28, UL33 and UL78 genes. G protein-coupled receptors (GPCR) are the largest family of cell surface proteins, found in organisms from yeast to humans. In this research, phylogenetic analysis was used to investigate the origins of the US27 and US28 genes, which are adjacent in the viral genome. The results indicate that …

Rescuing Perishable Neuroanatomical Information From A Threatened Biodiversity Hotspot: Remote Field Methods For Brain Tissue Preservation Validated By Cytoarchitectonic Analysis, Immunohistochemistry, And X-Ray Microcomputed Tomography, Daniel Hughes, Ellen Walker, Paul Gignac, Anais Martinez, Kenichiro Negishi, Carl Lieb, Eli Greenbaum, Arshad Khan

Selected Works Temporary Series

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, areincreasingly threatened. There is a need to accelerate collection efforts in these regionsbefore threatened or endangered species become extinct. The diverse geographical, ecological,genetic, morphological, and behavioral data generated from the on-site collection ofan individual specimen are useful for many scientific purposes. However, traditional methodsfor specimen preparation in the field do not permit researchers to retrieve neuroanatomicaldata, disregarding potentially useful data for increasing our understanding of braindiversity. These data have helped clarify brain evolution, deciphered relationships betweenstructure and function, and revealed constraints and selective pressures that provide contextabout the evolution …

Rescuing Perishable Neuroanatomical Information From A Threatened Biodiversity Hotspot: Remote Field Methods For Brain Tissue Preservation Validated By Cytoarchitectonic Analysis, Immunohistochemistry, And X-Ray Microcomputed Tomography, Hughes, Ellen Walker, Paul Gignac, Anais Martinez, Kenichiro Negishi, Carl Lieb, Eli Greenbaum, Arshad Khan

Departmental Papers (Biology)

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, areincreasingly threatened. There is a need to accelerate collection efforts in these regionsbefore threatened or endangered species become extinct. The diverse geographical, ecological,genetic, morphological, and behavioral data generated from the on-site collection ofan individual specimen are useful for many scientific purposes. However, traditional methodsfor specimen preparation in the field do not permit researchers to retrieve neuroanatomicaldata, disregarding potentially useful data for increasing our understanding of braindiversity. These data have helped clarify brain evolution, deciphered relationships betweenstructure and function, and revealed constraints and selective pressures that provide contextabout the evolution …

Impacts From The Use Of Antibiotics In Livestock: Methods Of Transmission Of Antibiotic Resistance From Livestock To Humans, Kristin M. Walden

Biology: Student Scholarship & Creative Works

Antibiotic use in livestock production has been around since the 1950s. Antibiotic feed is used in livestock and other meat producing animals for three reasons: illness prevention, illness treatment, and growth promotion. Unfortunately, since the time that antibiotics were first invented, antibiotic resistant bacteria have become a threat to public health. There are many studies showing methods of transmission of antibiotic resistance from livestock to humans. Antibiotic resistance can spread from livestock to soil, water, insects, and food, which ultimately comes into contact with humans. A proposed study to measure antibiotic resistance when eliminating antibiotic feed will provide a hypothesis …

Germline Defects Caused By Smed-Boule Rna-Interference Reveal That Egg Capsule Deposition Occurs Independently Of Fertilization, Ovulation, Mating, Or The Presence Of Gametes In Planarian Flatworms, Jessica Kathryne Steiner, Junichi Tasaki, Labib Rouhana

Biological Sciences Faculty Publications

Few animals are known to lay eggs in the absence of ovulation or copulation, as it is presumably energetically wasteful and subjected to negative selection. Characterization of Smed-boule, a member of the DAZ family of germline RNA-binding proteins, revealed that egg capsule (or capsule) production and deposition occurs independently of the presence of gametes in the planarian flatworm Schmidtea mediterranea. Reduction of Smed-boule expression by RNA-interference (RNAi) causes ablation of spermatogonial stem cells and the inability of ovarian germline stem cells to undergo oogenesis. Although animals subjected to Smed-boule RNAi lose their gametes and become sterile, they continue …

Effect Of Bisphenol-A On Neurodevelopment In Drosophila Melanogaster Larvae, Alexandra M. Streifel

All College Thesis Program, 2016-2019

This paper examines the effects of the chemical preservative bisphenol-A on the developing nervous systems of Drosophila melanogaster, or fruit fly, larvae. This study examines the effects of bisphenol-A using both behavioral as well as morphological paradigms. It was determined that bisphenol-A significantly increased the amount of time larvae spent in seeking behavior, the number of peristaltic contractions, and the distance traveled in a linear fashion. In the morphological analysis, indications of increased dendritic area in experimental larvae existed, but there was not enough data to determine significance. For future research, it is recommended that more data be gathered to …

The Effect Of Interspecies Signaling On Stenotrophomonas Maltophilia Growth., Zachary Ethan Dickinson

College of Arts & Sciences Senior Theses

Cystic fibrosis (CF) is a genetic disorder that effects over 70,000 people worldwide, and is particularly prevalent in those of Caucasian descent. CF increases susceptibility to chronic infections of the lungs and GI tract, often leading to decreased quality of life and early death to afflicted individuals. No cure is available, and so treatment is limited to treating the frequent infections that afflict CF patients. Several species of bacteria are commonly implicated in these infections, including Stenotrophomonas maltophilia. Infections of this species is of particular interest as it has been shown to be highly antibiotic resistant. This is a concern …