We study intracellular trafficking of the chloride channel CFTR in heterologous systems and in primary human airway epithelial cultures. The most common mutation in cystic fibrosis, deltaF508, results in a misassembled protein that is retained at the ER but can escape and proceed to the plasma membrane by addition of small molecule correctors or low temperature incubation. Temperature-rescued deltaF508 disappears rapidly from the cells surface and is subjected to lysosomal degradation, while wild-type CFTR is recycled back to the plasma membrane. Of particular interest is the mechanism that leads to elimination of detlaF508 from the cell surface.
We are interested in uncovering the fundamental systems-wide processes and mechanisms that underlie life, with a human-health focus. We apply a combination of both modern and traditional tools to this pursuit, including bioinformatics, proteomics, microarrays, molecular genetics, bench work, and software development. Current research areas we focus on include: 1) locating the molecular mechanisms that underlie antibiotic tolerance in the bacteria Pseudomonas aeruginosa, to address the threat that drug resistant organisms pose to those with COPD and Cystic Fibrosis; 2) annotation of the human genome with proteomic data, to determine which genes are translated and when, and how those correlate with prevalent diseases such as cancer; 3) development of computational agent-based models of intramolecular pathways and pathogen-host interactions in HIV, to determine how host-pathogen interactions relate to disease progression; 4) development of software tools for analysis of RNA structures, such as the viral HIV genome, to assist with determining how RNA structure impacts function; and 5) developing software for finding post-translational modifications (PTMs) on proteins by integrating proteomic data sets, to determine the role that these play on cellular signaling in healthy and diseased states. We have a wide diversity lab members, from microbiology bench scientists to computer scientists, and would be a great fit for a student looking for a broad, cross-disciplinary training environment focused on either microbiology and/or genomics.
Dr. Gilmore’s research group is applying state-of–the-art magnetic resonance imaging and image analysis techniques to study human brain development in 0-6 year olds, with a focus on cortical gray and white matter development. Studies include normally developing children, twins, and children at high risk for schizophrenia and bipolar illness. We are beginning to study the contributions of specific genes of risk to brain development in humans. A collaborative study with the Harlow Primate Lab at the University of Wisconsin is using imaging to study brain development in Rhesus monkeys, and the impact of prenatal exposure to maternal infection on brain development.
Successful respiratory pathogens must be able to respond swiftly to a wide array of sophisticated defense mechanisms in the mammalian lung. In histoplasmosis, macrophages -- a first line of defense in the lower respiratory tract -- are effectively parasitized by Histoplasma capsulatum. We are studying this process by focusing on virulence factors produced as this "dimorphic" fungus undergoes a temperature-triggered conversion from a saprophytic mold form to a parasitic yeast form. Yersinia pestis also displays two temperature-regulated lifestyles, depending on whether it is colonizing a flea or mammalian host. Inhalation by humans leads to a rapid and overwhelming disease, and we are trying to understand the development of pneumonic plague by studying genes that are activated during the stages of pulmonary colonization. [note: Dr. Goldman will be moving to UNC in Summer 2008]
We are using C. elegans embryos to address fundamental issues such as how cells move to specific positions during embryonic morphogenesis, how the orientation of cell division is determined, how the mitotic spindle is positioned in cells and how cells respond to cell signaling. We use diverse methods, including methods of cell biology, developmental biology, forward and reverse genetics including RNA interference, biochemistry, molecular biology and live microscopy of cells and the cytoskeleton. We are also developing water bears as a
new model system to study the evolution of development.
Our primary research is in the area of computational systems biology, with particular interest in the study of biological signaling networks; trying to understand their structure, evolution and dynamics. In collaboration with wet lab experimentalists, we develop and apply computational models, including probabilistic graphical and multivariate methods along with more traditional engineering approaches such as system identification and control theory, to current challenges in molecular biology and medicine. Examples of recent research projects include: prediction of protein interaction networks, multivariate modeling of signal transduction networks, and development of methods for integrating large-scale genomic data sets.
We are interested in how complex signaling systems interact to preserve homeostasis, while also optimizing the response of the organism to environmental changes. Two different projects are ongoing in the laboratory: Project 1: Matching renal salt excretion with dietary salt intake is vital for survival. We are integrating whole animal physiological studies and innovative molecular techniques to investigate the role of a new intestinal hormone, uroguanylin, in this process. Project 2: How do target organs communicate with neural circuits? We are investigating feedback regulation of a simple neural circuit that uses a novel form of muscle-to-nerve communication to control the contractions of the heart musculature.
Our research goal is to understand how bacterial pathogens cause disease on their hosts. We are working with a plant pathogen, Pseudomonas syringae which introduces virulence proteins into host cells to suppress immune responses. Our laboratory collaborates with Jeff Dangl's lab in the UNC Biology Department using genomics approaches to identify P. syringae virulence proteins and to discover how they alter plant cell biology to evade the plant immune system and cause disease.
Our lab is studying the role of mitogen and stress-activated protein kinases to regulate key aspects of cell metabolism. We are also studying signalling by tyrosine kinases in response to toxicological agents or cell stress.
We are interested in basic DNA-protein interactions as related to - DNA replication, DNA repair and telomere function. We utilize a combination of state of the art molecular and biochemical methods together with high resolution electron microscopes.
The primary thrust of research in this lab seeks to understand the effects of neurosteroids on development, particularly how neurosteroid levels in the developing cortex affect patterns of migration and neurogenesis in the prefrontal cortex. A secondary interest is the mechanisms by which increases in neurosteroid levels might be relevant to their therapeutic action.
Dr. Gulley's research is on Epstein-Barr virus (EBV)-related malignancies. Molecular and immunohistochemical techniques are used to characterize infected tissues. We validate new assays to help diagnose and monitor affected patients.
The Gupta group uses statistical and computational approaches to find conserved stochastic patterns or motifs in genome sequences. They are particularly interested in using these approaches to discover gene regulatory modules and interaction networks involved in specific biological processes.
