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Broad And Potent Neutralizing Antibody Responses Elicited In Natural Hiv-2 Infection, Rui Kong Jan 2011

Broad And Potent Neutralizing Antibody Responses Elicited In Natural Hiv-2 Infection, Rui Kong

All ETDs from UAB

Little is known about the potency, breadth and epitope specificities of neutralizing antibody (Nab) responses elicited in natural HIV-2 infection. Analysis of plasma specimens from 64 HIV-2 chronically-infected subjects in a single round infectivity assay (JC53bl-13/TZM-bl) revealed median reciprocal IC50 Nab titers of 1.7x105, 2.8x104 and 3.3x104 against three primary virus strains, HIV-27312A, HIV-2ST and HIV-2UC1, respectively. A subset of 5 plasma samples was tested on 17 additional HIV-2 strains, and similarly high Nab titers were observed against all but four viruses. These Nab titers were higher, by orders of magnitude, than HIV-1 Nab titers in plasma from chronically infected …

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Sox2/Parylated Parp1 Complexes Regulate Pluripotency, Yi-Shin Lai Jan 2011

Sox2/Parylated Parp1 Complexes Regulate Pluripotency, Yi-Shin Lai

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Embryonic stem cells (ESCs) were first derived from the inner cell mass (ICM) of blastocyst-stage embryos. ESCs are distinguished from other cell types by their pluripotency and unlimited self-replication. ESCs are able to differentiate into multiple cell types that represent all three primary germ layers (ectoderm, mesoderm and endoderm) and can form an entire adult organism. Under defined conditions, ESCs are self-renewable and have an extended life-span without compromising pluripotency. The plasticity of ESCs provides opportunities for regenerative medicine. The recent production of induced pluripotent stem cells (iPSC) offers an ideal "personalized" substitute for ESCs. Overexpression of four transcription factors, …

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The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz Jan 2011

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz

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THE ROLE OF TRIB3 IN INSULIN RESISTANCE: ITS ACTION AS NUTRIENT SENSOR AND REGULATOR OF INSULIN ACTION JIARONG LIU LAMIQUIZ PATHOLOGY ABSTRACT Insulin resistance is a hallmark of Type 2 diabetes (T2DM). A reduced capacity for insulin to stimulate increases in glucose uptake and glucose oxidation in insulin sensitive tissues, such as skeletal muscle and adipose tissue, are common defects in patients with insulin resistance, T2DM, and other related diseases. Tribbles homolog 3 (TRIB3) has been demonstrated to play a role in insulin resistance by serving as a negative regulator of Akt in mouse liver, fat, and pancreas. In a …

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Structural And Functional Studies On Group A Streptococcal Bacteriophage Hyaluronidase, Joo Hyoung Lee Jan 2011

Structural And Functional Studies On Group A Streptococcal Bacteriophage Hyaluronidase, Joo Hyoung Lee

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Aberrant hyaluronan production is frequently associated with tumors where the elevated levels of tumoral hyaluronan are often associated with higher expression levels of cellular hyaluronidases that produce saturated hyaluronan fragments with divergent pro-tumoral activities. In this thesis, we provide evidence that different hyaluronan metabolism of bacteriophage hyaluronidase (HylP) elicits distinct alteration in breast cancer cell behavior. We demonstrate through comparative analysis with bovine testicular hyaluronidase (BTH) that higher enzyme activity, specificity for hyaluronan and production of unsaturated oligosaccharides render HylP to have profound effects on growth, migration and invasion activities of breast carcinoma cells, whereas BTH and its saturated metabolites …

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In Vivo Interactions Between Virus Genomes And Host Proteins For Members Of The Order Picornavirales, Erik Michael Lenarcic Jan 2011

In Vivo Interactions Between Virus Genomes And Host Proteins For Members Of The Order Picornavirales, Erik Michael Lenarcic

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A significant number of pathogens of economical and medical importance are positive sense RNA viruses. Their genomes enter host cells and subvert them to support virus growth. These large-scale changes involve the co-opting of cellular proteins through interactions with viral RNA and proteins. Characterizing these interactions leads to a better understanding of viral life cycles and the identification of new antiviral therapies. The order Picornavirales contains viruses that infect a wide array of eukaryotes. Their genomes serve as a messenger RNA (mRNA) that is translated by host ribosomes cap-independently through an internal ribosome entry site (IRES). Most members of the …

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Post-Transcriptional Control Of Type I Interferon Genes By Ksrp In The Innate Immune Response Against Viral Infection, Wei-Jye Lin Jan 2011

Post-Transcriptional Control Of Type I Interferon Genes By Ksrp In The Innate Immune Response Against Viral Infection, Wei-Jye Lin

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Several strategies are used in eukaryotic cells in order to determine the gene expression level, including the transcriptional and post-transcriptional mechanisms. One of the post-transcriptional mechanisms is the regulation of mRNA stability, which varies considerably from one mRNA species to another. Previous studies have shown that inherently unstable mRNAs encoding cytokines and proto-oncogenes contain the AU-rich elements (AREs) in the 3' untranslated regions (UTRs). Their decay requires decay-promoting RNA-binding proteins that recognize the AREs and recruit mRNA decay machineries to facilitate the rapid decay of targeting mRNA. KH-type splicing regulatory protein (KSRP) was previously identified as an ARE decay promoting …

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Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu Jan 2011

Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu

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Changes in the glioma microenvironment including oxygen (O2) levels, supply of amino acid such as L-glutamate and L-cystine and glutathione (GSH) concentrations play a critical role in glioma biology. Previous data from our laboratory and others have implicated the L-cystine/L-glutamate exchanger, system xc- in the invasion and proliferation of cancers including glioma. The central aim of this dissertation was to characterize the contribution of L-cystine uptake, GSH synthesis and L-glutamate release to migration and proliferation of glioma cells. In my first study, I examined the role of system xc- mediated L-glutamate release on glioma migration. I show that activation of …

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Regulation Of Neuronal Death By The Autophagy Lysosomal Pathway: Implications For Parkinson Disease, Violetta N. Pivtoraiko Jan 2011

Regulation Of Neuronal Death By The Autophagy Lysosomal Pathway: Implications For Parkinson Disease, Violetta N. Pivtoraiko

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Parkinson Disease (PD) is the second most common age-related neurodegenerative disorder and is characterized pathologically by the loss of dopaminergic (DA) neurons in the stubstantia nigra pars compacta (SNpc). Mitochondrial dysfunction, increased oxidative stress, and accumulation of aggregated α-synuclein (α-syn), an intracellular protein involved in synaptic function, are all pathological hallmarks of PD have been implicated in PD pathogenesis. However, it is debated whether α-syn aggregates themselves are responsible for neurodegeneration in PD, cellular pathways involved in degradation of α-syn aggregates are believed to promote neuron survival. The autophagy lysosomal pathway (ALP), a physiological mechanism for recycling of intracellular components, …

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Myosin Ii In Hippocampal Synapses: Regulation Of Synaptic Plasticity, Strength And Actin Dynamics By Two Distinct Isoforms, Maria Dolores Rubio Jan 2011

Myosin Ii In Hippocampal Synapses: Regulation Of Synaptic Plasticity, Strength And Actin Dynamics By Two Distinct Isoforms, Maria Dolores Rubio

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Cytoskeletal actin filaments underlie dendritic spine plasticity, critical for several forms of learning and memory. Therefore, understanding the mechanisms that regulate actin dynamics is essential to elucidate memory formation pathways. Myosins, a superfamily of actin binding proteins, have emerged as candidates for regulation of actin dynamics in the brain. Several myosin class II isoforms have been identified in brain, but their individual contribution to synaptic activity is still unknown. Based on the finding that myosin IIB regulates actin polymerization in the growth cone of developing neurons and that it is necessary for maintenance of dendritic spine structure, I hypothesized that …

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The Natural History Of Sivcpz Infection In Wild Living Chimpanzees, Rebecca Steele Rudicell Jan 2011

The Natural History Of Sivcpz Infection In Wild Living Chimpanzees, Rebecca Steele Rudicell

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Simian immunodeficiency virus of chimpanzees (SIVcpz) is the immediate precursor to human immunodeficiency virus type 1 (HIV-1), but even the most basic aspects of SIVcpz infection in its natural host are unknown. Here, we present the first comprehensive analysis of the natural history of SIVcpz infection in wild living chimpanzees. Using non-invasive (feces and urine based) methods, we studied two unique chimpanzee populations in Tanzania: the famous chimpanzees of Gombe National Park and the savanna chimpanzees of Ugalla, located about 135 km southeast of Gombe. Gombe chimpanzees are endemically infected with SIVcpz, and the park's established research infrastructure provides a …

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The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans Jan 2011

The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans

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Statins, a widely prescribed class of cholesterol-lowering drug, inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. Due to the identification of cholesterol as a risk factor for developing Alzheimer's disease (AD), a number of studies have examined whether statins are neuroprotective against developing AD or dementia. While some epidemiological studies do indicate a lower prevalence of AD in people taking statins, other reports are contradictory. A consensus has therefore not been reached regarding the neuroprotective effects of statin treatment. Aside from the well-characterized reduction in circulating cholesterol resulting from statin therapy, numerous cholesterol-independent, pleiotropic effects have been …

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Gabaergic Signaling To Adult-Generated Neurons In Hippocampus, Sean Markwardt Jan 2011

Gabaergic Signaling To Adult-Generated Neurons In Hippocampus, Sean Markwardt

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In the central nervous system of adult mammals, new neurons are produced throughout life in at least two regions, the subventricular zone and dentate gyrus of the hippocampus. New neurons in the SVZ migrate via the rostral migratory stream and eventually participate in adaptive olfactory processes. In the dentate gyrus, a variety of physiological functions for continued addition of neurons have been proposed, but its role in normal or pathological conditions remains largely unclear. Neurogenesis in the dentate gyrus consists of the stepwise process of generating fully functional granule cells (GCs) from adult neural stem cells. Regulation of neurogenesis can …

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Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova Jan 2011

Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova

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Primary cilia are antenna-like organelles that extend from the surface of almost all mammalian cell types. They regulate many signaling pathways and sense physical and chemical changes in the extracellular environment. Defects in primary cilia cause several human disorders of different severity collectively called ciliopathies, including nephronophthisis (NPHP), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). Numerous MKS, JBTS and NPHP genes have been identified but in most cases of these ciliopathies the genetic defect is unknown. Despite the fact that NPHP, JBTS and MKS patients present with distinct clinical features, they have mutations in identical genes. This can be explained …

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Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell Jan 2011

Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell

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In this dissertation we describe knockin mouse models for the study of human hemoglobin disorders. These knockin human globin genes, in contrast to transgenes, replace the adult mouse globin genes, remain under control of endogenous mouse globin enhancer sequences and are inherited in a manner identical to globin alleles in man. Starting with various knockin alleles composed of unique human alpha, beta and gamma globin gene sequences, we evaluate several allele combinations towards our goal of generating improved models of thalassemia and sickle cells disease. We show that humanized knockin mice complete a fetal to adult hemoglobin switch during postnatal …

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Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin Jan 2011

Role Of Calcium-Activated Potassium Channels In Glioblastoma Volume Regulation, Michael Bryan Mcferrin

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The most common and most malignant gliomas are the Grade IV Glioblastoma Multiforme (GBM), characterized by a highly proliferative tumor mass and extremely invasive phenotype that allows for profuse dispersal of tumor cells throughout the brain. GBM cells must specifically regulate their cell volume to thrive within the edematous tumor mass and infiltrate throughout the tortuous extracellular spaces of the brain. These rapid and directed volume changes are governed by the controlled flux of potassium and chloride ions across the cell membrane, which move osmotically obliged water. The goal of this dissertation was to investigate the role of calcium-activated potassium …

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Killer Immunoglobulin-Like Receptors And Human Leukocyte Polymorphisms In Hiv-1 Pathogenesis, Aimee Marie Merino Jan 2011

Killer Immunoglobulin-Like Receptors And Human Leukocyte Polymorphisms In Hiv-1 Pathogenesis, Aimee Marie Merino

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Human leukocyte antigen (HLA) molecules influence the adaptive and innate immune responses through interactions with cytotoxic T lymphocytes and natural killer cells (NK). HLA influence the activation state of NK through direct binding to killer immunoglobulin-like receptors (KIR) and presentation of HLA-derived peptides to NKG2 receptors. Activated NK can kill HIV-infected cells through direct cytolysis and release cytokines that influence other aspects of the immune system. Variations in KIR gene content and allelic variants have been associated with autoimmunity, transplantation success, and infectious diseases such as hepatitis C and HIV/AIDS. We investigated the impact of KIR genes and potential KIR-HLA …

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The Role Of Cd19 In Follicular Dendritic Cell Activation, Riley Croom Myers Jan 2011

The Role Of Cd19 In Follicular Dendritic Cell Activation, Riley Croom Myers

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Germinal Centers (GC) are organized foci in secondary lymphoid organs of birds and mammals and are the principle sites of memory B cell generation and plasma cell formation. GC concentrate antigen within follicles to facilitate recognition by responding B cells to promote somatic hypermutation and affinity maturation. Follicular dendritic cells (FDC) reside within the light zones of GC and serve to facilitate B cell interactions with antigen, as well as B cell selection, proliferation, and survival. The work contained within this dissertation addresses the collaborative interactions between B cells and FDC. FDC within an active, GC-containing follicle express an array …

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Pediatric Obesity And Traumatic Lower Extremity Long Bone Fracture Outcomes, Ian Charles Backstrom Jan 2011

Pediatric Obesity And Traumatic Lower Extremity Long Bone Fracture Outcomes, Ian Charles Backstrom

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Background: Pediatric obesity is associated with lower extremity injuries and poor outcomes after blunt trauma. Our aim was to determine if obese pediatric patients with femur and tibia fractures have more severe injury patterns and worse outcomes compared to non-obese patients. Methods: We performed a retrospective cohort study of obese and non-obese pediatric patients with femur or tibia fractures treated at two Level-1 trauma centers from 2004-2010. Patients weighing ≥ 95th percentile for age and gender were classified as obese. Patients were compared regarding demographics, Injury Severity Score (ISS), intra-abdominal, and orthopedic injuries. Outcomes included fracture treatment, orthopedic complications, ICU …

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Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky Jan 2011

Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky

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Our laboratory reported that a combination of ionizing radiation (IR) or temozolomide (Tmz), a DNA methylating agent clinically approved against glioblastoma multiforme (GBM), a type of human brain cancer, and TRA-8, an anti-DR5 monoclonal antibody produced synergistic cytotoxicity in GBM cells in culture and in mouse xenograft models through an yet unknown mechanism. I hypothesized that understanding of the synergy phenomenon can offer an insight into the nature of GBM vulnerability. The goals of this investigation were two-fold - to elucidate the mechanism of this enhancement in cytotoxicity, and to improve understanding of DR5 mediated apoptosis toward improvement of current …

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Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland Jan 2011

Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland

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The recently characterized exopolysaccharide of Mycoplasma pulmonis, EPS-I, has been identified as modulating the susceptibility to complement-mediated lysis and binding to host mucosal epithelium. M. pulmonis produces family of size- and phase-variable lipoproteins called Vsa. Previous evidence has strongly demonstrated that the length of the tandem repeat region of the M. pulmonis Vsa protein is associated with the susceptibility to the host innate immune system through complement-mediated lysis. Mycoplasmas producing a long form of Vsa, containing about 40 repeats, are resistant complement whereas strains that produce the short form of Vsa, 5 repeats or fewer, are susceptible. Furthermore, the size …

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Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley Jan 2011

Mechanisms And Consequences Of Thy-1 Shedding, John Edwin Bradley

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Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic fibrosis in the lung interstitium of unknown etiology, and causes death within 2 to 4 years after diagnosis. There are no clinical interventions save for lung transplantation that give any survival benefit. Aberrant collagen deposition and aggregates of proliferating fibroblasts and myofibroblasts called fibroblastic foci (FF) are the classic features of IPF. Therefore, the cell type most often implicated as pathogenic in IPF is the fibroblast, especially its differentiated phenotype, the myofibroblast. Fibroblasts are a remarkably heterogeneous cell type. Expression of the cell surface glycoprotein Thy-1 (Thymocyte differentiation antigen 1) delineates a …

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Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Fetterman Jan 2011

Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Fetterman

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While progress has been made in understanding the development and progression of cardiovascular disease (CVD), the mechanisms of CVD risk and initiation are not completely understood. It is widely accepted that CVD is the result of a combination of genetic and environmental factors but it is not known why some populations with otherwise similar risk factors appear more susceptible to CVD than others. It is also known that different strains of laboratory mice have distinct susceptibilities to CVD development. For example, C3H mice are resistant to diet induced atherogenesis whereas C57 animals are susceptible. We have also found that the …

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Role Of Ras Proteins In Malignant Peripheral Nerve Sheath Tumors, Nicole Marie Brossier Jan 2011

Role Of Ras Proteins In Malignant Peripheral Nerve Sheath Tumors, Nicole Marie Brossier

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Malignant peripheral nerve sheath tumors (MPNSTs) arising in patients with neurofibromatosis type I (NF1) are null for the tumor suppressor neurofibromin, a negative regulator of signaling from both classic Ras (H-Ras, N-Ras and K-Ras) and R-Ras (R-Ras, R-Ras2/TC21, M-Ras/R-Ras3) subfamily members. Treatment of these tumors with Ras-targeted agents such as farnesyltransferase inhibitors has proven unsuccessful, likely due to the inability of these agents to successfully target all of the Ras isoforms regulated by neurofibromin. Thus, determining which Ras isoforms are critical for MPNST pathogenesis would be of therapeutic value. In this dissertation, we first review the clinical manifestations of NF1 …

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Identification And Characterization Of Novel Adenosine Cleavage Enzymes In Mycobacteria, Kajal Buckoreelall Jan 2011

Identification And Characterization Of Novel Adenosine Cleavage Enzymes In Mycobacteria, Kajal Buckoreelall

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Tuberculosis (TB) is one of the leading infectious diseases in the world. An estimated one third of the world's population is infected with Mycobacterium tuberculosis, the causative pathogen of TB. With the emergence of drug resistant strains of the mycobacterium, and the HIV-TB coinfection epidemic, TB remains a global health emergency. Purine metabolism is an essential cellular component to all living cells. Previous studies have shown that differences exist between mycobacterial and human purine metabolism. One of the differences was in the metabolism of adenosine (Ado), whose cleavage was observed in mycobacterial cells whereas Ado cleavage is inefficient in human …

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High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang Jan 2011

High Resolution Analysis Of Clonal Pluripotent Stem Cell Lentiviral Gene Therapy In A Mouse Model Of Beta-Thalassemia, Rui Yang

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Gene therapy for hematopoietic disorders using viral vectors has achieved significant clinical benefit. However this approach has been held back by adverse genotoxic events due to random viral integration into the genome. A better understanding of viral transgene chromosomal position effects is critical for the design of safer viral vectors and clinical protocols. However, detailed analysis of viral transgenes is hampered by the heterogeneity of the viral-transduced bone marrow cell populations. I hypothesized that viral transduction of pluripotent stem cells would enable the clonal analysis of viral transgene expression, safety, and efficacy both in vitro and in vivo. Here I …

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Assessment Of Mitochondrial Stressors On Cellular Bioenergetics, Blake Reid Zelickson Jan 2011

Assessment Of Mitochondrial Stressors On Cellular Bioenergetics, Blake Reid Zelickson

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The mitochondrion plays a central role in the maintenance of bioenergetic function through the production of ATP and essential metabolites. The development of mitochondrial bioenergetic defects is a hallmark of important pathologies such as cardiovascular and liver diseases. It is well established that a decrease in mitochondrial function, typically of 20-40%, is associated with the progression of these pathologies. Causal relationships have been more difficult to establish because of the challenge of assessing mitochondrial function in a cellular setting. Specifically, it is known that mitochondria function at less than their maximal respiratory capacity and the remainder, known as reserve or …

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Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang Jan 2011

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang

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The most common genetic diseases worldwide, £] thalassemia and Sickle Cell Anemia (SCA) result from mutations in the adult £] globin gene. One promising therapeutic method to ameliorate these diseases is to reactivate the endogenous fetal f× globin gene. I hypothesize that an erythroid mutagenic transposon system can be used to activate f× globin gene expression. To test this hypothesis three lines of genetically modified mice were generated and bred together. The first is a transgenic mouse line that contains a multicopy array of erythroid mutagenic PiggyBac (PB) transposons. The second transgenic mouse line expresses the PB transposase (TPase) from …

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Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham Jan 2011

Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham

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DYT1 dystonia is an inherited movement disorder caused by a trinucleotide deletion (DeltaGAG) in the DYT1 (TOR1A) gene, which codes for the torsinA protein. Dr. Yuqing Li's laboratory previously reported the characterization of a DYT1 dystonia mouse model, a knock-in carrying DeltaGAG in Dyt1 (KI), which displays a motor learning deficit of motor skill transfer. We report here that this motor learning deficit was reversed with an anticholinergic drug, trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. We further show a potential substrate for the pathophysiology, a reduction in D2 receptors in the striatum in …

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Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook Jan 2011

Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook

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Sulfation is an important Phase II drug metabolism reaction catalyzed by the cytosolic sulfotransferases (SULTs). SULT2A1 is a major SULT in liver and adrenal cortex that has been reported to sulfate a wide variety of substrates including bile acids, steroids, and drugs. The crystal structures of SULT2A1 suggest that PAPS binding causes a structural change. This study examines the kinetic changes in SULT2A1 caused by PAPS binding using computer modeling, enzyme kinetics, binding studies, and mammalian cells expressing SULT2A1. The data presented clearly demonstrate that the binding of PAPS changes the affinity of some substrates to SULT2A1 resulting in different …

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Understanding Molecular Mechanisms Of Breast Cancer Metastasis Using Genetically-Engineered Mice, Leah M. Cook Jan 2011

Understanding Molecular Mechanisms Of Breast Cancer Metastasis Using Genetically-Engineered Mice, Leah M. Cook

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Morbidity and mortality of breast cancer patients are drastically increased when primary tumor cells metastasize to distant organ sites. Effective treatment of metastatic disease has been limited; therefore, an increased molecular understanding to identify biomarkers and therapeutic targets is needed. Breast cancer metastasis suppressor 1 (BRMS1) suppresses development of metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Little is known of Brms1 function throughout the initiation and progression of mammary carcinoma. Thus Brms1 transgenic mice (derived on C57BL/6 background) were generated by utilizing MMTV promoter expression (for mammary-selective overexpression) or the beta-actin promoter (for ubiquitous …

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