Medicine and Health Sciences Commons^™

A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu

NYMC Faculty Publications

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased …

Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …

Effect Of Hydrogen Peroxide On The Biosynthesis Of Heme And Proteins: Potential Implications For The Partitioning Of Glu-TrnaGlu Between These Pathways, Carolina Farah, Gloria Levicán, Michael Ibba, Omar Orellana

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Glutamyl-tRNA (Glu-tRNA^Glu) is the common substrate for both protein translation and heme biosynthesis via the C5 pathway. Under normal conditions, an adequate supply of this aminoacyl-tRNA is available to both pathways. However, under certain circumstances, Glu-tRNA^Glu can become scarce, resulting in competition between the two pathways for this aminoacyl-tRNA. In Acidithiobacillus ferrooxidans, glutamyl-tRNA synthetase 1 (GluRS1) is the main enzyme that synthesizes Glu-tRNA^Glu. Previous studies have shown that GluRS1 is inactivated in vitro by hydrogen peroxide (H₂O₂). This raises the question as to whether H₂O₂ negatively affects …

Gaip Interacting Protein C-Terminus Regulates Autophagy And Exosome Biogenesis Of Pancreatic Cancer Through Metabolic Pathways, Santanu Bhattacharya, Krishnendu Pal, Anil K. Sharma, Shamit K. Dutta, Julie S. Lau, Irene K. Yan, Enfeng Wang, Ahmed Elkhanany, Khalid M. Alkharfy, Arunik Sanyal, Tushar C. Patel, Suresh T. Chari, Mark R. Spaller, Debabrata Mukhopadhyay

Dartmouth Scholarship

GAIP interacting protein C terminus (GIPC) is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular …

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …

Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/ disulfide balance in cells. In this study, we investigated whether Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knock-out (KO) mice and age-matched wild-type (WT) mice ages 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than …

Measuring The Role Of Inhibition In Auditory Discrimination In Mice, Tazima Nur

Graduate Theses and Dissertations

Understanding how inhibitory neurons affect sensory information processing in the cerebral cortex is an ongoing goal of both neuroscience and statistical physics research. In this master's thesis research project, an experimental system has been designed and built for studying how auditory dynamic range depends on inhibitory neurons, based on observations of mouse behavior. In this thesis, firstly, the topic of inhibition and information processing has been introduced. Then two papers related to inhibition and dynamic range has been reviewed in detail. One of the papers is an experimental work that analyzes the affect of inhibition on dynamic range. The other …

Redesign Of Trans-Splicing Molecules For The Correction Of Dystrophia Myotonica Type 1 Toxic Rna Transcripts, Eleanor G. Harrison

Undergraduate Honors Theses

Dystrophia myotonica (DM1), one of the most common forms of muscular dystrophy, is caused by a repeated trinucleotide expansion in the DMPK gene. This mutation results in the accumulation of toxic cellular RNA transcripts. Spliceosome-mediated RNA trans-splicing (SMaRT) technology is a form of gene therapy that possesses the potential to correct these toxic RNA transcripts and thus cure the disease. Despite its promise, prior research applications of SMaRT technology to DM1 have been hampered by poor efficiency and have not been validated in a relevant model of the disease. In order to improve the efficiency of trans-splicing, this study examined …

Modulation Of T Lymphocytes By Tumor-Released Survivin, Jessica Marie Jutzy

Loma Linda University Electronic Theses, Dissertations & Projects

The tumor microenvironment is an area of intense interaction between normal and malignant cells. Factors and cell types within this environment can play a crucial role in the progression or regression of the tumor. Of primary interest are tumor-infiltrating T lymphocytes, which have been shown to have a key role in modifying the dynamics of the tumor microenvironment to promote or prevent tumor growth. While there is much in vitro and in vivo evidence for a modification of the tumor infiltrating T cell population toward a pro-tumor environment, what induces these changes within the tumor microenvironment has remained elusive. Our …

Regulation Of C-Reactive Protein Gene Expression And Function, Avinash N. Thirumalai

Electronic Theses and Dissertations

Human C-reactive protein (CRP) is the prototypic acute phase protein whose serum concentration increases rapidly during inflammation. CRP is also associated with atherosclerosis; it is deposited at lesion sites where it may interact with modified lipoproteins. There are 2 major questions regarding CRP: 1. How is the serum concentration of CRP regulated? 2. What are the functions of CRP in atherosclerosis?

Our first aim was to determine the role of the constitutively expressed transcription factor Oct-1 in regulating CRP gene expression. We found that Oct-1 overexpression inhibited (IL-6+IL-1β)- induced CRP gene expression; maximal inhibition required the binding of Oct-1 to …

Synchronous Opening And Closing Motions Are Essential For Camp-Dependent Protein Kinase A Signaling, Atul K. Srivastava, Leanna R. Mcdonald, Alessandro Cembran, Jonggul Kim, Larry R. Masterson, Christopher L. Mcclendon, Susan S. Taylor, Gianluigi Veglia

Larry Masterson

Acquisition And Reconstruction Techniques For Fat Quantification Using Magnetic Resonance Imaging, Abraam S. Soliman

Electronic Thesis and Dissertation Repository

Quantifying the tissue fat concentration is important for several diseases in various organs including liver, heart, skeletal muscle and kidney. Uniquely, MRI can separate the signal from water and fat in-vivo, rendering it the most suitable imaging modality for non-invasive fat quantification. Chemical-shift-encoded MRI is commonly used for quantitative fat measurement due to its unique ability to generate a separate image for water and fat. The tissue fat concentration can be consequently estimated from the two images. However, several confounding factors can hinder the water/fat separation process, leading to incorrect estimation of fat concentration.

The inhomogeneities of the main …

The Pathological Effects Of Ccr2+ Inflammatory Monocytes Are Amplified By An Ifnar1-Triggered Chemokine Feedback Loop In Highly Pathogenic Influenza Infection, Sue-Jane Lin, Ming Lo, Rei-Lin Kuo, Shin-Ru Shih, David M. Ojcius, Jean Lu, Chien-Kuo Lee, Hui-Chen Chen, Meei Yun Lin, Chuen-Miin Leu, Chia-Ni Lin, Ching-Hwa Tsai

All Dugoni School of Dentistry Faculty Articles

Background: Highly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration of leukocytes into the lungs, high viral loads and a cytokine storm. However, the details of how these pathological features unfold in severe influenza infections remain unclear. Accumulation of Gr1 + CD11b + myeloid cells has been observed in highly pathogenic influenza infections but it is not clear how and why they accumulate in the severely inflamed lung. In this study, we selected this cell population as a target to investigate the extreme inflammatory response during severe influenza infection.

Results: We established H1N1 IAV-infected mouse models using …

Er-Associated Degradation And Cadmium Dependent Rescue Of Pca1, Nathan Smith

Department of Biochemistry: Dissertations, Theses, and Student Research

Protein synthesis and proper folding is an essential process for all organisms. In eukaryotes proteins of the secretory pathway are synthesized and inserted into the lumen or membrane of the endoplasmic reticulum. Eukaryotic cells maintain a mechanism for removal of proteins unable to fold properly. This process is known as ER-associated degradation (ERAD). A poorly functioning ERAD can lead to a build-up of misfolded proteins which has been implicated in several degenerative diseases such as Alzheimer’s, Amyotrophic lateral sclerosis, and Parkinson’s. Thus, the study of how proteins are recognized, extracted from the ER, and degraded is essential for determining methods …

Nanofluidity Of Fatty Acid Hydrocarbon Chains As Monitored By Benchtop Time-Domain Nuclear Magnetic Resonance, David P. Cistola

David P Cistola

The functional properties of lipid-rich assemblies such as serum lipoproteins, cell membranes, and intracellular lipid droplets are modulated by the fluidity of the hydrocarbon chain environment. Existing methods for monitoring hydrocarbon chain fluidity include fluorescence, electron spin resonance, and nuclear magnetic resonance (NMR) spectroscopy; each possesses advantages and limitations. Here we introduce a new approach based on benchtop time-domain 1H NMR relaxometry (TD-NMR). Unlike conventional NMR spectroscopy, TD-NMR does not rely on the chemical shift resolution made possible by homogeneous, high-field magnets and Fourier transforms. Rather, it focuses on a multiexponential analysis of the time-decay signal. In this study, we …

Cross-Disciplinary Sciences At Gettysburg College: Second Annual Poster Presentation, X-Sig

Student Publications

This booklet includes Biology student presentations by: Taylor Bury, Abigail Dworkin-Brodsky, Mary Pearce, Jasper Leavitt, Morgan Panzer, Ellen Petley, Kalli Qutub, Taylor Randell, Samantha Eck, Lana McDowell, Jenn Soroka, Celina Harris, Natalie Tanke, Alexandra Turano, and Caroline Garliss.

This booklet includes Biochemistry & Molecular Biology student presentations by: Matthew Dunworth, Andrew Sydenstricker, Brianne Tomko, Albert Vill, Warren Campbell, David Van Doren, Kevin Mrugalski, Stacey Heaver, Alecia Achimovich, and Katherine Boas.

This booklet includes Chemistry student presentations by: Kristen Baker, Laura Lee, Kathryn Fodale, Daniel Ruff, Michael Counihan, Ida DiMucci, Joshua Sgroi, Celina Harris, and Natalie Tanke.

This booklet include Health …

Characterization Of Severe Fever With Thrombocytopenia Syndrome In Rural Regions Of Zhejiang, China, Lei Zhang, Ling Ye, David M. Ojcius, Xiuyu Lou, Chengwei Wang, Cen Feng, Yi Sun, Zhongfa Wang, Shibo Li, Yanjun Zhang

All Dugoni School of Dentistry Faculty Articles

Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011–2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be …

A Cytoplasmic Rna Virus Generates Functional Viral Small Rnas And Regulates Viral Ires Activity In Mammalian Cells, Kuo-Feng Weng, Chuan-Tien Hung, Po-Ting Hsieh, Mei-Ling L. Li, Guang-Wu Chen, Yu-An Kung, Peng-Nien Huang, Rei-Lin Kuo, Li-Lien Chen, Jing-Yi Lin, Robert Yung-Liang Wang, Shu-Jen Chen, Petrus Tang, Jim-Tong Horng, Hsing-I Huang, Jen-Ren Wang, David M. Ojcius, Gary Brewer, Shin-Ru Shih

All Dugoni School of Dentistry Faculty Articles

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10⁵ copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced …

Differential Muscle Hypertrophy Is Associated With Satellite Cell Numbers And Akt Pathway Activation Following Activin Type Iib Receptor Inhibition In Mtm1 P.R69c Mice, Michael Lawlor, Marissa Viola, Hui Meng, Rachel Edelstein, Fujun Liu, Ke Yan, Elizabeth Luna, Alexandra Lerch-Gaggl, Raymond Hoffmann, Christopher Pierson, Anna Buj-Bello, Jennifer Lachey, Scott Pearsall, Lin Yang, Cecilia Hillard, Alan Beggs

Elizabeth J. Luna

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence …

Hydroxamic Acid-Based Histone Deacetylase (Hdac) Inhibitors Can Mediate Neuroprotection Independent Of Hdac Inhibition, Sama Sleiman, Yan-Ling Zhang, Jennifer Gale, Manuela Basso, Giovanni Coppola, John T. Pinto, Rajiv Ratan

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibition improves function and extends survival in rodent models of a host of neurological conditions, including stroke, and neurodegenerative diseases. Our understanding, however, of the contribution of individual HDAC isoforms to neuronal death is limited. In this study, we used selective chemical probes to assess the individual roles of the Class I HDAC isoforms in protecting Mus musculus primary cortical neurons from oxidative death. We demonstrated that the selective HDAC8 inhibitor PCI-34051 is a potent neuroprotective agent; and by taking advantage of both pharmacological and genetic tools, we established that HDAC8 is not critically involved in PCI-34051's …

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

John Loy

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen. Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were generated and …

The Potential Of Quinoline Derivatives For The Treatment Of Toxoplasma Gondii Infection., Sirinart Ananvoranich

Chemistry and Biochemistry Publications

Here we reported our investigation, as part of our drug repositioning effort, on anti-Toxoplasma properties of newly synthesized quinoline compounds. A collection of 4-aminoquinoline and 4-piperazinylquinoline analogs have recently been synthesized for use in cancer chemotherapy. Some analogs were able to outperform chloroquine, a quinoline derivative drug which is commonly used in the treatment of malaria and other parasitic infections. Herein 58 compounds containing one or two quinoline rings were examined for their effectiveness as potential anti-Toxoplasma compounds. Of these 58 compounds, 32 were efficient at inhibiting Toxoplasma growth (IC50μM). Five compounds with single and simple quinoline rings exhibited similar …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Host Cell Death In Legionella Pneumophila Pathogenesis And Immunity, Wenhan Zhu

Open Access Dissertations

Legionella pneumophila is an intracellular pathogen that causes a severe, atypical pneumonia termed Legionnaires' disease. Upon entering the host cell, L. pneumophila resides in a membrane-bound vacuole, in which the bacterium evades lysosomal fusion and replicates. The establishment of the vacuole requires the Dot/Icm (Defect in organelle trafficking/ intracellular multiplication) transport system, which translocates a large number of substrates into host cells to re-orchestrate various cellular processes, such as intracellular trafficking, protein synthesis and host cell death pathways. Therefore, a key step in understanding the biology of Legionella is to dissect the mechanisms of action of the Dot/Icm substrates. By …

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster., Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …

Identification And Characterization Of Protein Kinase C Substrates In Human Breast Cells, Xin Zhao

Dissertations, Theses, and Capstone Projects

Aberrations in PKC signaling can lead to the development of multiple human diseases and the most prominent association of PKC with disease has been in tumor growth and metastasis. PKC and its related pathways have been recognized as promising targets for blocking the malignancy of breast cancer cells. To better understand PKC-mediated pathway in breast cancer cells, it is important to identify the cellular substrates of PKC. The main focus of this work is to identify physiologically relevant cellular substrates of PKC in human breast cells and to characterize their roles in cancer-related phenotypes. The work to be described consists …

The Non-Canonical Hydroxylase Structure Of Yfcm Reveals A Metal Ion-Coordination Motif Required For Ef-P Hydroxylation, Kan Kobayashi, Assaf Katz, Andrei Rajkovic, Ryohei Ishii, Owen E. Branson, Michael A. Freitas, Ryuichiro Ishitani, Michael Ibba, Osamu Nureki

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

EF-P is a bacterial tRNA-mimic protein, which accelerates the ribosome-catalyzed polymerization of poly-prolines. In Escherichia coli, EF-P is post-translationally modified on a conserved lysine residue. The post-translational modification is performed in a two-step reaction involving the addition of a β-lysine moiety and the subsequent hydroxylation, catalyzed by PoxA and YfcM, respectively. The β-lysine moiety was previously shown to enhance the rate of poly-proline synthesis, but the role of the hydroxylation is poorly understood. We solved the crystal structure of YfcM and performed functional analyses to determine the hydroxylation mechanism. In addition, YfcM appears to be structurally distinct from any …

Mistranslation Of The Genetic Code, Adil Moghal, Kyle Mohler, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

During mRNA decoding at the ribosome, deviations from stringent codon identity, or “mistranslation,” are generally deleterious and infrequent. Observations of organisms that decode some codons ambiguously, and the discovery of a compensatory increase in mistranslation frequency to combat environmental stress have changed the way we view “errors” in decoding. Modern tools for the study of the frequency and phenotypic effects of mistranslation can provide quantitative and sensitive measurements of decoding errors that were previously inaccessible. Mistranslation with non‐protein amino acids, in particular, is an enticing prospect for new drug therapies and the study of molecular evolution.

A Rational Framework For Evaluating The Next Generation Of Vaccines Against Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Murray E. Hines Ii, Luiz E. Bermudez, Adel M. Talaat, Srinand Sreevatsan, Judith R. Stabel, Yung-Fu Chang, Paul M. Coussens, Raúl G. Barletta, William C. Davis, Desmond M. Collins, Yrjö T. Gröhn, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Since the early 1980s, several investigations have focused on developing a vaccine against Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease in cattle and sheep. These studies used whole-cell inactived vaccines that have proven useful in limiting disease progression, but have not prevented infection. In contrast, modified live vaccines that invoke a Th1 type immune response, may improve protection against infection. Spurred by recent advances in the ability to create defined knockouts in MAP, several independent laboratories have developed modified live vaccine candidates by transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate …