My research focuses on developing biologically based models for the uptake, distribution, metabolism, and biological effects of drugs and chemicals and their application to safety assessments and quantitative health risk assessments. In recent years, my research emphasis has been on developing mathematical descriptions of control of genetic circuitry and the dose-response and risk-assessment implications of these control processes.
The goal of our laboratory is to investigate mechanisms of tumorigenesis and tumor progression, and to apply genome-wide techniques to develop anti-cancer therapies. Our research focuses on transcriptional regulation of gene expression during stem cell self-renewal and differentiation and during tumorigenesis. We use artificial transcription factors (ATFs) as genetic probes to identify genes and gene pathways responsible for the appearance of specific malignant phenotypes and we investigate the ability of these ATFs to interfere with tumor cell regulatory programs. Cancer cell reprogramming with such artificial “genetic switches” may afford a new therapeutic strategy.
My lab uses a cognitive neuroscience approach to understand the neurobiology of drug addiction in humans. The tools we use include fMRI, cognitive testing, physiological monitoring, pharmacology, and genetic testing. We specifically seek to determine 1) how the brain learns new stimulus-response associations and replaces learned associations, 2) the neurobiological mechanisms underlying the tendency to select immediate over delayed rewards, and 3) the neural bases of addiction-related attentional bias.
Research in the Carelli laboratory is in the area of behavioral neuroscience. Our studies focus on the neurobiological basis of motivated behaviors, including drug addiction. Electrophysiology and electrochemistry procedures are used during behavior to examine the role of the brain 'reward' circuit in natural (e.g., food) versus drug (e.g., cocaine) reward. Studies incorporate classical and operant conditioning procedures to study the role of the nucleus accumbens (and dopamine) and associated brain regions in learning and memory, as they relate to motivated behaviors.
Developing and applying novel mass spectrometry (MS)-based proteomics methodologies for high throughput identification, quantification, and characterization of the pathologically relevant changes in protein expression, post-translational modifications (PTMs), and protein-protein interactions. Focuses in the lab include: 1) technology development for comprehensive and quantitative proteomic analysis, 2) investigation of systems regulation in toll-like receptor-mediated pathogenesis and 3) proteomic-based mechanistic investigation of stress-induced cellular responses/effects in cancer pathogenesis.
Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes
Research in the lab is focused on four major areas - (1) Genetic, cellular, and genomic analyses of Drosophila CNS development, (2) Brain development and behavior, (3) Molecular genetics of gene regulatory pathways, and (4) Control of cell migration and fusion events.
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.
My interests focus on developing quantiative methods to assess the relationships between exposure, dose and response. This research has examined methods for dioxins, thyroid hormone disruptors and pyrethroid pesticides.
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 Dokholyan group focuses primarily on understanding protein dynamics, more specifically on how induced changes in protein folding and aggregation lead to diseases, such as cystic fibrosis, many types of cancers, and a number of neurodegenerative diseases. The Dokholyan group focuses on several such diseases, including Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, and Huntington disease. The Dokholyan group is developing a hierarchy of molecular models, from simplified coarse-grained models to more detailed ones, to create a novel multi-scale simulation methodology. This methodology will enable simulations of large molecular complexes at the biologically-relevant time scales, thereby allowing to directly glance into processes associated with human diseases. Member of the Molecular & Cellular Biophysics Training Program.
The Elston lab is interested in understanding the dynamics of complex biological systems, and developing reliable mathematical models that capture the essential components of these systems. The projects in the lab encompass a wide variety of biological phenomena including signaling through MAPK pathways, noise in gene regulatory networks, airway surface volume regulation, and understanding energy transduction in motor proteins. A major focus of our research is understanding the role of molecular level noise in cellular and molecular processes. We have developed the software tool BioNetS to accurately and efficiently simulate stochastic models of biochemical networks
The role of associative learning and memory in cue-induced relapse to drug seeking and the role of the prefrontal cortex in suppression of drug seeking. Studies in my laboratory utilize surgical, behavioral, and histological techniques as well as neuropharmacological manipulations.
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.
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.
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.
Dynamic control of signaling networks in living cells; Rho family and MAPK networks in motility and network plasticity; new tools to study protein activity in living cells (i.e., biosensors, protein photomanipulation, microscopy). Member of the Molecular & Cellular Biophysics Training Program and the Medicinal Chemistry Program.
Structure, dynamics and function of viral domains in biomembranes. Photomanipulation and traction mapping applied to the migration of single cells. Investigation of the mechanochemical basis of cell oscillations using systems biology approaches coupled with experiments.
The goal of my research is to identify, clone, and characterize the evolution of genes underlying natural adaptations in order to determine the types of genes involved, how many and what types of genetic changes occurred, and the evolutionary history of these changes. Specific areas of research include: 1) Genetic analyses of adaptations and interspecific differences in Drosophila, 2) Molecular evolution and population genetics of new genes and 3) Evolutionary analysis of QTL and genomic data.
Research in the Kaufmann laboratory is concerned with determining the mechanisms whereby cell cycle checkpoints suppress human cancer development. We are focused on two checkpoints that help to stabilize the genome. The decatenation G2 checkpoint delays mitosis until daughter chromatids are sufficiently disentangled by topoisomerase II. This checkpoint is regulated by the breast cancer susceptibility gene BRCA1. The intra-S checkpoint regulates DNA synthesis by controlling the rates of replicon initiation and DNA chain elongation. This checkpoint is regulated by two proteins, Timeless and Tipin, that mediate signaling at stalled replication forks. A program project is studying how the Timeless-Tipin replication fork protection complex protects against UV-induced chromosomal damage and sunlight-induced melanoma.
We use high-throughput DNA sequencing, microarrays, and other technologies to study how and where proteins interact with the genome, and how these interactions affect the biology of living cells. We use three systems: yeast, C. elegans and human. Our C. elegans studies focus on developmental processes, and we use human cell lines and clinical samples to study diseases like cancer and diabetes. All of our projects focus on chromatin and DNA-binding proteins.
Dr. Macdonald is the Founder and Scientific Director of the new Metabolomic Facility and Co-Scientific Director of the joint UNC/NCSU/NOAA Marine MRI facility at Pivers Island near Beaufort NC. Dr. Macdonald's research goal is to combine metabolomics and tissue engineering and apply these tools to quantitative biosystem analysis.
We are interested in the mechanisms by which histone protein synthesis is coupled to DNA replication, both in mammalian cell cycle and during early embryogenesis in Drosophila, Xenopus and sea urchins.
Protein-derived radicals, in vivo detection of free radical generation, biomarkers of oxidative stress and free radical formation in aids-related infection (Pseudomonas aeruginosa)
We are a theoretical physical chemistry group in the Department of Chemistry at the University of North Carolina at Chapel Hill. We use advanced computational methods to study biological processes at multiple scales, from single protein functional dynamics and chromatin folding and stability to cell-level processes, such as stochastic signal transduction and regulation of cell motility.
Dr. Pomp studies the genetic architecture of complex traits, with an emphasis on body weight regulation and obesity. Using polygenic mouse models and high throughput approaches integrating genomics and physiology, he identifies genes that control predisposition to a variety of complex traits including energy intake and energy expenditure (e.g. voluntary exercise). In addition, Dr. Pomp studies how these genes interact with each other, with changing environments such as nutritional interventions, and with other diseases such as cancer.
Regulation of plant development: We use techniques of genetics, molecular biology, microscopy, physiology, and biochemistry to study how endogenous developmental programs and exogenous signals cooperate to determine plant form. The model plant Arabidopsis thaliana has numerous technical advantages that allow rapid experimental progress. We focus on how the plant hormone auxin acts in several different developmental contexts. Among questions of current interest are i) how auxin regulates patterning in embryos and ovules, ii) how light modifies auxin response, iii) how feedback loops affect kinetics or patterning of auxin response, iv) how flower opening and pollination are regulated, and v) whether natural variation in flower development affects rates of self-pollination vs. outcrossing.
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The nucleus accumbens is a limbic-motor integrator, assimilating memory and drive input and coordinating responsive behavioral output. Anatomical and pharmacological evidence indicates that the core and shell subregions of the nucleus accumbens perform overlapping but distinct roles in motivated behavior. My experiments examine nucleus accumbens core and shell function during ethanol drinking behavior in rats, with particular focus on how dopamine input modulates accumbal activity on the millisecond timescale. I use two approaches: electrophysiological firing patterns of neurons in the nucleus accumbens core and shell are evaluated using multi-electrode arrays, and phasic (subsecond) dopamine activity is evaluated using fast-scan cyclic voltammetry. I am also interested in exploring the pharmacological manipulation of neuronal transmission in the nucleus accumbens, focusing on drugs that have clinical therapeutic value in treating alcoholism.
Bioinformatics, Cancer Biology, Cell Biology, Chemical Biology, Computational Biology, Genomics, Molecular Medicine, Neurobiology, Pharmacology, Systems Biology, Toxicology, Translational Medicine
Our laboratory is examining the role of histone post-translational modifications in chromatin structure and function. Using a combination of molecular biology, genetics and biochemistry, we are determining how a number of modifications to the histone tails (e.g. acetylation, phosphorylation, methylation and ubiquitylation) contribute to the control of gene transcription, DNA repair and replication.
I study complex traits using linkage, association, and genetic epidemiological approaches. Disorders include schizophrenia (etiology and pharmacogenetics), smoking behavior, and chronic fatigue.
The mechanical properties, force response and force generating mechanisms of biological systems is of great interest for physiological function, for tissue engineering and embryogenesis and for drug delivery. In collaboration with the Computer Science Department, we develop and apply new technologies for applying and measuring forces on single molecules, cells and tissue cultures. In collaboration with the departments of Mathematics, Computer Science, Chemistry and the UCN Cystic Fibrosis Center we are pursuing an integrated computational model of mucus clearance in the lung. Affiliated with the Molecular & Cellular Biophysics Training Program.
Our laboratory uses the mouse as a model to study phenotypes with complex etiologies contributed by genetic and environmental factors and that underlie differences in susceptibility to common diseases. Genetics and a broad range of genomic, bioinformatic and computational tools are used in a new integrative field called systems genetics. Through many collaborative interactions, major research foci are currently in development, reproduction, neurobiology, cancer (colon and breast), cardiology, exposure biology and computational genetics. Our laboratory is also investigating the function role of the Egfr/Erbb gene family of receptor tyrosine kinases through embryonic stem cell manipulation, transgenics, gene targeting and other genetic engineering technologies.
Topics include gene discovery, genomics/proteomics, gene transcription, signal transduction, molecular immunology. Disease relevant issues include infectious diseases, autoimmune and demyelinating disorders, cancer chemotherapy, gene linkage.
The Wilhelmsen lab is engaged in the genetic mapping of susceptibility loci for complex neurological diseases and has been developing large-scale automated gene mapping technologies to facilitate these mapping efforts. They have invested heavily in automation that enables high-throughput genotyping and data processing. As data accumulates, this will enable parametric and nonparametric linkage analysis of large numbers of traits at regular intervals for the entire genome. The Wilhelmsen lab is applying these techniques to two projects: (1) the genetics of alcoholism and (2) positional cloning of the gene responsible for a family of disorders called frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).
