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Anesthesiology
A comparative study examining techniques for analysis of firing patterns of hippocampal place cells across multiple neurons, during sleep and rest in rats.
Biological Chemistry
Eukaryotic Initiation Factor 1A (elF1A) is one of many key factors in protein synthesis. By PCR, cloning and sequencing, phosphorylated mutants of elF1A will be made at the amino acid position Ser 125 and the effectiveness of this position on elF1A will be studies on the basis of cell viability, growth rates and protein synthesis rates.
Translation initiation factors are appearing as novel oncogenes and tumor progression markers. In this project, I will quantitatively analyze the expression of subunits of the initiation factor, elF3, in cancer and normal cells. the overexpression of subunits in cancer cells can possibly be used as a prognostic marker, which can advance the treatment for patients with cancer.
In my first experiment, I will find out whether or not a human protein (p44) within the eIF3 subunit can replace a similar protein (p33) in yeast. The second experiment will answer how the p44 protein interacts and affects the binding of eIF3 to the ribosomal complex in human cells.
To further characterize the properties of eIF3g, gene deletions of eIF3g will be over expressed in mammalian cell lines and analyzed for phenotypic differences.
Cancer Center
Constitutively activated components of the phosphatidylinositol 3-kinase-Akt pathway will be expressed in the three human bladder cell lines to test their potential in tumor progression.
Create a Tandem Affinity Purification Fusion Protein construct with the ASGP2 portion of Muc4. Use fusion protein to isolate and identify proteins that interact with ASGP2.
Cardiovascular Medicine
The project aims to teach techniques for both isolation of mouse cardiac myocytes and patch-clamp electrophysiological analysis of the individual cells. In this project, we will analyze electrophysiological differences between ion channels in mouse cardiac myocytes, which have been maintained in culture for different period of time.
Cell Biology & Human Anatomy
I will investigate whether anucleated fibers cells contain the structural machinery for protein synthesis, and determine the location of protein synthesis in the mouse lens.
Center for Genetics
The purpose of this experiment is to study and characterize a proposed enhancer pathway involved in C. elegans nuclear migration.
Center for Neuroscience
This study examines the brains ability to adapt to its environment. Neurons in the brain change structurally in response to learning. These structural changes come about through changes in gene expression. By studying the sound localization ability in Barn owls we can pinpoint the area of the brain where these structural changes are occurring. Using a technique known as Serial analysis of Gene Expression we will monitor and compare which genes are being expressed in these neurons. This will allow us a better understanding of the cellular mechanisms involved with structural changes that create adaptive behaviors.
My research will study how congenital blindness (lack of visual input from birth) affects the development of cortical conncections in the brains of juvenile animals.
Developmental & Behavioral Pediatrics
Assessment of fine motor skills and visual motor integration in children with sex chromosome aneuploidy to further describe the developmental profile for this patient population.
Human Physiology
The aim of this proposal is to investigate the chronic effects of estrogen on sodium, calcium, and proton accumulation during ischemia (lack of blood flow) and reperfusion (return of flow) in isolated rat hearts. Maintaining homeostasis of these ions is imperative in normal heart function. Although there has been evidence that estrogen protects the heart during ischemia, recent clinical studies have shown that estrogen replacement therapy in post-menopausal women may add more detrimental risks than benefits. This proposal aims to study the ionic mechanisms involved in estrogen's effect on myocardium during ischemia in order to explore and understand the general effects of acute and chronic treatments of estrogen.
Internal Medicine
I would like to explore the role of cellular apoptosis (cell death) in modified arterial permeability in old and young rats by examining the role heat shock protein 60 (HSP60).
Myeloperoxidase (MPO), an enzyme implicated in inflammatory diseases, binds to different cells and lipoproteins upon its release by white blood cells. The purpose of this study is to identify binding motifs for MPO using a combinatorial chemistry approach.
Evaluates whether hyperhomocysteinemia increases arterial permeability and whether low folate exacerbates the effects of hyperhomocysteinemia. Additionally, this project investigates the underlying mechanisms of hyperhomocysteinemia and low folate in elevating permeability. Mice heterozygous for the cystathionine -synthase (CBS) gene will be used as an experimental model, and permeability will be measured using quantitative fluorescence microscopy on carotid arteries.
To test the effects of Lefty-A gene overexpression in hepatic stellate cells on the production of collagen type I ( ), a main component of extra cellular matrix, and tissue inhibitor of metal proteinase-1 (TIMP-1), an inhibitor of collagenases that break down various types of collagen.
I want to study the effect of an emerging cardiovascular risk factor, hyperhomocysteinemia, on carotid arterial compliance. Arterial compliance is important because it is the ability of a blood vessel to increase diameter in response to increased blood pressure and thereby allow an increase in blood flow. Further, I wish to evaluate a mechanism that may be responsible for hyperhomocysteinemia-evoked reduction in arterial compliance.
Medical Dermatology
I will study the effects of hydrogen peroxide on EGF receptor phosphorylation in wound healing.
Medical Microbiology & Immunology
I propose to prepare a novel polymerized HIV-1 vaccine and determine the immunogenicity of this vaccine in mice.
In this study, we will examine the regulation pathway of Bcl-2, a family of anti-apoptotic proteins, by inhibiting calpain expression in MCF7 (breast cancer) cells overexpressing cyclin E.
RNA inhibition and microarray analysis will be employed to identify genes regulated by calpain, a protease involved with cell adhesion, migration, and metastasis in MCF7 breast cancer cells overexpressing Cyclin E.
Serum collected from "healthy" sea otters will be evaluated for the presence of antibodies to the fungus Coccidioides immitis using Enzyme Linked Immunosorbent Assay (ELISA). This project involves two phases: I - the development and optimization of an ELISA for the detection of Coccidioidal antibody in sea otters, II - testing serum collected from healthy sea otters for these antibodies using the above method.
This project will identify twenty babA negative strains of Helicobacter pylori, and determine if recombination occurred between the babA gene and the babB gene.
The purpose of this study is to investigate the production of cytokines IFN-j and IL-2 in response to infection by Nocardia asteroides in the murine brain.
When Cyclin E is overexpressed in certain Breast Cancer cell lines, a persistence of a hyperactive Lower-Molecular-Weight Isoforms of Cyclin E appears. I propose to over-express Cyclin E in a multitude of different cell lines to see if this "clipped" form of Cyclin E is a characteristic of tumorgenesis.
I will develop a method for producing and using amplicon-style HSV-1 vectors and phage *C31 integrase for gene transfection and integration into mammalian cells.
The goal of this project is to demonstrate that lifespan and immunity are linked through insulin signaling pathways in mosquitoes.
Using the novel gene therapy vector I have designed, I will test for effective delivery and expression of a human protein sequence in vitro.
Medical Pathology
I will study the effects contact lenses may have on contact lens users. Computer-assisted intravital microscopy will be used to examine and quantify microvascular abnormalities in vivo in contact lens users. The possible microvascular changes such as abnormal vessel diameter, thickened vessel walls, blocked vessels, abnormal red-blood cell velocity, etc. will be identified to lead to a better understanding of damages that contact lenses may cause.
Analysis of viral localization in the host cell in response to mutations in the nuclear localization signal of the Nef Protein.
Medical Phamacology & Toxicology
The goal of the project is to identify candidate genes regulated by the transcription factor MAD3 using the mouse cerebelllu as a model system.
The analysis of prostate cancer tissue microarrays will identify stage specific protein signatures for the development of more accurate diagnostic tools and cancer treatments.
Neurological Surgery
Behavioral tests, including the Morris Watermaze and Beam Walk, as well as histologic tests are performed on an experimental group and two control groups of rats to determine if a novel laser therapy for epilepsy causes injury to normal brain function.
The project will study the effects of stem cell implantation into damaged neural tissue. Stem cells have the ability to differentiate into different cell types, including those found in the brain, depending on the environmental cues it receives within the body. Bone marrow stem cells, acquired from donor rats, will be injected into a specified area within the rats' brains. The results of the survival and differentiation of flourescenctly-labeled stem cells within the injured brain will be compared to that of the uninjured brain to eliminate the effects of any other factor.
Neurology
In this study, we propose to investigate the effects of administering UCD 026 on the growth of brain tumor cells using intracerebral implantation of the human glioma cell line U87 in athymic rats as an experimental model. The potential tumoricidal properties of UCD 026 will be examined by initiating treatment on postimplantation day 10 and continuing treatment for 10 days. The volumes of the tumors will be determined successively using proton nuclear magnetic resonance (1H-NMR) and confirmed terminally on day 20 by sacrificing the animal and using histological staining and stereology. Tumor growth during this 10 day treatment with UCD 026 will be compared to a standard growth curve of untreated animals to determine if the drug kills tumors, has anti-proliferative activity, or does both.
Novel therapeutics are needed for treating human glioblastoma. This project will screen specially synthesized drugs in cell culture and the most efficacious drugs in vivo.
I propose to use anti-AChR monoclonal antibodies to cure the long open times of the slow channel congenital myasthenic acetylcholine receptors.
Pathology
This project will be a continuation of an ongoing experiment in which our research group is investigating the relationship between inflammation and elevated levels of the sulfur amino acid homocysteine in plasma (hyperhomocysteinemia). This research may provide insight into the recognized association between vascular disease and hyperhomocysteinemia.
Use computer-assisted intravital microscopy to study the bulbar conjunctiva of dogs (microcirculation) during shock to correlate with systemic readings.
I will study the effects of vasopressin on the microcirculation in hemorrhagic shock. Some of these effects are adverse and have never been previously studied.
Surgery
Utilizing a rat hemorrhage model, I will evaluate a new hemoglobin-based solution and compared it to hetastarch and shed blood. Physiologic responses will be monitored.