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Table of contents
- Laboratory of Structure-Function Based Drug Design – ИБМХ
- Books Endothelin: Molecular Biology, Physiology, and Pathology (Contemporary Biomedicine) Free
- PhD Program in Biomedical Sciences
- PhD Program in Biomedical Sciences
- BBSP Faculty
Although very distinct, these disorders share a common underlying pathogenic mechanism. Ultimately, this research will provide a platform for future drug discovery efforts against these devastating diseases. Our lab is studying the molecular mechanisms which are involved in the induction and proliferation and patterning of cardiac progenitor cell populations. To identify the molecular pathways involved in these processes, we have used Xenopus and mouse as model systems with particular focus on the endogenous role of genes implicated in the early steps of cardiogenesis and human congenital heart disease.
Present projects in the lab involve embryological manipulations, tissue explant cultures, molecular screens as well as protein-DNA interaction experiments, biochemistry and promoter analysis.
Laboratory of Structure-Function Based Drug Design – ИБМХ
My lab is focused on the improvement of treatment of chronic bacterial infections. We aim to determine the mechanisms of antibiotic tolerance. Our aim is to understand the physiology of the bacterial cell, primarily Staphylococcus aureus , during infection and how this physiology allows the cell to survive lethal doses of antibiotic.
The Cook lab studies the major transitions in the cell division cycle and how perturbations in cell cycle control affect genome stability.
We have particular interest in mechanisms that control protein abundance and localization at transitions into and out of S phase DNA replication phase and into an out of quiescence. We use a variety of molecular biology, cell biology, biochemical, and genetic techniques to manipulate and evaluate human cells as they proliferate or exit the cell cycle.
We collaborate with colleagues interested in the interface of cell cycle control with developmental biology, signal transduction, DNA damage responses, and oncogenesis. The primary research area my lab is the regulation of meiotic recombination at the genomic level in higher eukaryotes.
Genomic instability and disease states, including cancer, can occur if the cell fails to properly regulate recombination.
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We have created novel tools that give our lab an unparalleled ability to find mutants in genes that control recombination. We use a combination of genetics, bioinformatics, computational biology, cell biology and genomics in our investigations. A second research area in the lab is the role of centromere DNA in chromosome biology. We welcome undergraduates, graduate students, postdoctoral fellows and visiting scientists to join our team. Using Bordetella species as models, her group is studying the role of virulence gene regulation in respiratory pathogenesis, how virulence factors activate and suppress inflammation in the respiratory tract, and how proteins of the Two Partner Secretion pathway family are secreted to the bacterial surface and into the extracellular environment.
A second major project is focused on Burkholderia pseudomallei, an emerging infectious disease and potential biothreat agent. This research is aimed at understanding the role of autotransporter proteins in the ability of this organism to cause disease via the respiratory route. Our lab is interested in molecular mechanisms of oncogenesis, specifically as regulated by Ras and Rho family small GTPases. We are particularly interested in understanding how membrane targeting sequences of these proteins mediate both their subcellular localization and their interactions with regulators and effectors.
Both Ras and Rho proteins are targeted to membranes by characteristic combinations of basic residues and lipids that may include the fatty acid palmitate as well as farnesyl and geranylgeranyl isoprenoids.
Books Endothelin: Molecular Biology, Physiology, and Pathology (Contemporary Biomedicine) Free
The latter are targets for anticancer drugs; we are also investigating their unexpectedly complex mechanism of action. Finally, we are also studying how these small GTPases mediate cellular responses to ionizing radiation — how do cells choose whether to arrest, die or proliferate? The Cyr laboratory studies cellular mechanisms for cystic fibrosis and prion disease. We seek to determine how protein misfolding leads to the lung pathology associated with Cystic Fibrosis and the neurodegeneration associated with prion disease.
KSHV is associated with several types of cancer in the human population. We study the effect of KSHV viral proteins on cell proliferation, transformation, apoptosis, angiogenesis and cell signal transduction pathways. We also study viral transcription factors, viral replication, and the interactions of KSHV with the human innate immune system. Additionally, we are developing drug therapies that curb viral replication and target tumor cells. We use the premier model plant species, Arabidopsis thaliana, and real world plant pathogens like the bacteria Pseudomonas syringae and the oomycete Hyaloperonospora parasitica to understand the molecular nature of the plant immune system, the diversity of pathogen virulence systems, and the evolutionary mechanisms that influence plant-pathogen interactions.
All of our study organisms are sequenced, making the tools of genomics accessible. Research in the Darville lab is focused on increasing our understanding of immune signaling pathways active in development of genital tract disease due to Chlamydia trachomatis and determination of chlamydial antigen-specific T cell responses that lead to protection from infection and disease.
In vitro, murine model, and human studies are being performed with the ultimate goal to develop a vaccine against this prevalent sexually transmitted bacterial pathogen. Genetic and transcriptional microarray studies are being performed to explore pathogenic mechanisms and determine biomarkers of pelvic inflammatory disease due to Chlamydia as well as other sexually transmitted pathogens.
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With a particular interest in pediatric solid tumors, our lab aims to develop a mechanistic understanding of the role of aberrant or dysregulated transcription factors in oncogenesis. Our lab studies brain network connectivity in the healthy brain and in neurological and neuropsychiatric patient populations. We focus on the organizational, dynamical, and computational properties of large-scale brain networks and determine how these properties contribute to human behavior in health and disease. We strive to advance the basic understanding of brain structure and function, while making discoveries that can be translated to clinical practice.
Our research focuses on the immunological aspects of pathogen-host interactions. The lab is actively involved in HIV pathogenesis and vaccine studies using the nonhuman primate model of SIV infection. We are particularly interested in pediatric HIV transmission by breast-feeding and the early, local host immune response.
PhD Program in Biomedical Sciences
A main research focus is on developmental differences in host immune responses between infants and adults and how they alter pathogenesis. The effect of co-infections e. We study Borrelia burgdorferi the agent of Lyme disease as a model for understanding arthropod vector-borne disease transmission. We also study the epidemiology and pathogenesis of dengue viruses associated with hemorrhagic disease. Our research centers on understanding the molecular basis of human carcinogenesis. In particular, a major focus of our studies is the Ras oncogene and Ras-mediated signal transduction.
The goals of our studies include the delineation of the complex components of Ras signaling and the development of anti-Ras inhibitors for cancer treatment. Another major focus of our studies involves our validation of the involvement of Ras-related small GTPases e. We utilize a broad spectrum of technical approaches that include cell culture and mouse models, C. We study how mammalian cells regulate their survival and death apoptosis. We have focused our work on identifying unique mechanisms by which these pathways are regulated in neurons, stem cells, and cancer cells.
We utilize various techniques to examine this in primary cells as well as in transgenic and knock out mouse models in vivo. Our ultimate goal is to discover novel cell survival and death mediators that can be targeted for therapy in neurodegeneration and cancer.
PhD Program in Biomedical Sciences
The direct fabrication and harvesting of monodisperse, shape-specific nano-biomaterials are presently being designed to reach new understandings and therapies in cancer prevention, diagnosis and treatment. Students interested in a rotation in the DeSimone group should not contact Dr. DeSimone directly. Instead please contact Chris Luft at jluft email. There is a strong emphasis on translational research projects using a multi-disciplinary approach.
Thus, by using human in vivo models such as clinical studies we validate in vitro, epidemiology, and animal findings. A major focus of the Diekman lab is to develop new strategies to limit age-related osteoarthritis OA.
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The lab uses genetically-engineered mouse models to investigate the development of cellular senescence in joint tissues with physiologic aging. Our group has also developed genome-editing protocols for primary human chondrocytes to produce single-cell derived colonies with homozygous knockout of target genes.
We are using engineered tissues from these cells to dissect the mechanism of genes implicated in OA development by genome-wide association studies, as well as coupling these technologies to high throughput screening approaches for OA drug discovery. Sleep is an essential and evolutionarily conserved process that modifies synapses in the brain to support cognitive functions such as learning and memory. We are interested in understanding the molecular mechanisms of synaptic plasticity with a particular interest in sleep.
Using mouse models of human disease as well as primary cultured neurons, we are applying this work to understanding and treating neurodevelopmental disorders including autism and intellectual disability. The lab focuses on biochemistry, pharmacology, animal behavior and genetics. Our lab tries to understand viral pathogenesis.
Basic and translational studies address mechanisms of host defense, including recruitment and function of leukocytes, vascular permeability leading to edema, bacterial clearance and resolution. Cell signaling pathways initiated by binding of leukocyte-endothelial cell adhesion molecules and molecular mechanisms underlying the functions of neutrophils are two particular areas. We use an integrated approach genomics, proteomics, computational biology to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins regulators of G protein signaling and post-translational modifications including ubiquitination and phosphorylation.
The Dominguez lab studies how gene expression is controlled by proteins that bind RNA. RNA binding proteins control the way RNAs are transcribed, spliced, polyadenylated, exported, degraded, and translated. The overall focus of the laboratory is to develop immunotherapy strategies to treat human malignancies.
Specifically, one area of research is dedicated to the genetic engineering of immune cells to redirect their specificity to tumor-associated antigens. The most effective strategies developed in the laboratory are then translated into phase I clinical studies since we have access to the cellular therapeutic facility at UNC. The second area of research is dedicated to the tumor microenvironment and the development of engineering strategies aimed at countering its immunosuppressive properties. My lab studies how genes function within the three-dimensional context of the nucleus to control development and prevent disease.