Our research group utilizes the nematode C. elegans to investigate germ cell immortality: mechanisms that allow germ cells remain eternally youthful as they are transmitted from one generation to the next. We also study how telomerase functions at chromosome termini, as well as the consequences of telomere dysfunction.
Laminar organization of neurons in cerebral cortex is critical for normal brain function. Two distinct cellular events guarantee the emergence of laminar organization-- coordinated sequence of neuronal migration, and generation of radial glial cells that supports neurogenesis and neuronal migration. Our goal is to understand the cellular and molecular mechanisms underlying neuronal migration and layer formation in the mammalian cerebral cortex. Towards this goal, we are studying the following three related questions:
1. What are the signals that regulate the establishment, development and differentiation of radial glial cells, a key substrate for neuronal migration and a source of new neurons in cerebral cortex?
2. What are the signals for neuronal migration that determine how neurons reach their appropriate positions in the developing cerebral cortex?
3. What are the specific cell-cell adhesion related mechanisms that determine how neurons migrate and coalesce into distinct layers in the developing cerebral cortex?
We study the interface between signal transduction and cell function. Approaches employed include - molecular genetics, protein and lipid biochemistry, confocal and electron microscopy, protein crystallography, and model organisms approaches (e.g. yeast, Arabidopsis, C. elegans, mouse gene knockout technology).
Blood vessel formation in cancer and development; use mouse culture (stem cell derived vessels) and in vivo models (embryos and tumors); genetic, cell and molecular biological tools; how do vessels assemble and pattern?, dynamic image analysis.
Dr. Belger's research focuses on studies of the cortical circuits underlying attention and executive function in the human brain, as well as the breakdown in these functions in neuropsychiatric and neurodevelopment disorders such as schizophrenia and autism. Her research also examines changes in cortical circuits and their physiological properties in individuals at high risk for psychotic disorders. Dr. Belger combines functional magnetic resonance imaging, electrophysiological scalp recording, experimental psychology and neuropsychological assessment techniques to explore the behavioral and neurophysiological dimensions of higher order executive functions. Her most recent research projects have begun focusing on electrophysiological abnormalities in young autistic children and individuals at high risk for schizophrenia.
The Brenman lab studies how a universal energy and stress sensor, AMP-activated protein kinase (AMPK) regulates cellular function and signaling. AMPK is proposed to be a therapeutic target for Type 2 diabetes and Metabolic syndrome (obesity, insulin resistance, cardiovascular disease). In addition, AMPK can be activated by LKB1, a known human tumor suppressor. Thus AMPK signaling is not only relevant to diabetes but also cancer. We are interested in molecular genetic and biochemical approaches to understand how AMPK contributes to neurodegeneration, metabolism/cardiac disease and cancer.
Our lab is interested in the role of chromatin-modifying factors and epigenetics in mammalian development and disease. We are particularly interested in two major areas both of which make use of mouse models: (1) the role of BRG1 and SWI/SNF nucleosome-remodeling complexes in various aspects of hematopoiesis including regulation of globin gene expression and inflammation; (2) the role of dietary fiber and gut microflora on histone modifications, CpG methylation, and prevention of colorectal cancer.
It has been postulated for some time that cellular transplantation to the liver might allow for the reversal of hepatic based genetic defects or augmentation of hepatocellular function. However, the identification of the proper cell type and transplant conditions to produce liver engraftment and normal hepatocyte function has remained elusive. We have developed an alternative strategy using embryonic stem (ES) cells differentiated /in vitro/ and transplanted into hepatic parenchyma as “gene vectors” in order to restore wild type hepatocellular function.
Gene targeting and state-of-the-art phenotyping methods are used to elucidate the reproductive and cardiovascular roles of the adrenomedullin system and to characterize the novel GPCR-signaling mechanism of Adm’s receptor and RAMP’s.
This laboratory has worked for over 25 years investigating both fundamental and clinically relevant aspects of ciliary and flagellar motility in eukaryotic cells. Our primary focus has been the elucidation of the processes surrounding differentiation, function, and injury of mammalian airway ciliated epithelial cells and how these cells respond to challenge by infectious agents, environmental irritants including tobacco smoke, and pharmacologic agents. Our laboratory is also part of a large national center for diagnosis, research, and treatment of Primary Ciliary Dyskinesia, a genetic disease affecting mucociliary clearance of the airways. This laboratory is designed around facilitating light and electron microscopic
analyses but collaborates closely with other laboratories and colleagues working on cell and molecular biology topics in airway epithelial cell biology.
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.
The main research project is to determine the role of intercellular junctions in normal development, cell aging and cataract formation in human and animal lenses.
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.
Mechanisms of cell cycle control by cyclin dependent kinases (CDK's) and gene expression during Drosophila development, including how transcription factors (the pRB tumor suppressor and E2F), RNA metabolism (histone pre-mRNA processing), and protein ubiquitination and proteolysis (cullin dependent ubiquitin ligases) regulate the G1-S transition and DNA replication.
Investigation of genes/proteins that play key roles during embryonic and postnatal development of craniofacial/oral/dental structures; and their contribution to normal variation and to congenital and acquired disorders.
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.
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.
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.
The Neurotoxicology Group examines the role of microglia interactions with neurons and the associated immune-mediated responses in brain development and aging as they relate to the initiation of brain damage, the progression of cell death, and subsequent repair/regenerative capabilities. We have an interest in the neuroimmune response with regards to neurodegenerative diseases such as, Alzheimer's disease.
Our research focuses on determining the mechanisms responsible for craniofacial birth defects. We use the whole embryo culture system to expose mouse conceptuses to toxicants and evaluate morphological, molecular (Affy arrays) and protein changes. Antisense morpholinos and adenoviruses are used to modulate gene expression and determine phenotypic effects. We are using embryonic stem cells as a model to evaluate the effects of environmental chemicals on differentiation. Using molecular markers to identify differentiation may provide critical information to identify developmental toxicants.
We are studying how hemangioblasts, a bipotential precursor of endothelial and hematopoietic lineages, are specified and differentiated during development using zebrafish as a model system.
Effects of drugs of abuse on maternal behavior and aggression and the effects of prenatal exposure to drugs on offspring development and behavior. Approaches range from molecular to behavioral as our work is basic science with a clinically applicable focus.
Signal transduction coupled by heterotrimeric G proteins. We use Arabidopsis, genetics, biochemistry, & in vivo imaging of protein-protein interactions. The type of signals we study include light, hormones, & sugars.
Hormones influence virtually every aspect of plant growth and development. My lab is examining the molecular mechanisms
controlling the biosynthesis and signal transduction of the
phytohormones cytokinin and ethylene, and the roles that these hormones play in various aspects of development. We employ genetic, molecular, biochemical, and genomic approaches using the model species Arabidopsis to elucidate these pathways.
Our focus is on using genetic methods to improve transplantation using ES and hematopoietic stem cells in transplant models. A second focus of the lab uses mutant mice to examine potential drug targets for ameliorating radiation-induced lung damage.
Lab research signals and effectors necessary to establish regional and cellular differences in the regions of the forebrain. Human diseases are a starting point for identifying novel genes that may participate in normal forebrain development.
Specialized cell types allow plants to shed their structures-such as leaves, flowers and fruit-through the carefully orchestrated process of cell separation. The research focus of the Liljegren lab is to investigate the molecular mechanisms that control cell separation using the Arabidopsis flower as a model system. As in many other higher plants, Arabidopsis flowers contain pattern elements which allow distinct separation events such as floral organ shedding, fruit opening, pollen dehiscence, and seed dispersal to take place during their life cycle. Currently, we are characterizing the functions of key regulators of floral organ separation, including NEVERSHED, LOVES-ME-NOT and STAMENSTAY. We have discovered that NEVERSHED regulates vesicle trafficking during flower development and are using sensitized genetic screens to identify additional components of a signaling pathway, such as the receptor-like kinase EVERSHED, that likely control the movement and secretion of specific molecules during the shedding process.
My research goals are to identify the mechanisms by which environmental factors regulate smooth muscle cell phenotype and to define the transcriptional pathways that regulate SMC-specific gene expression.
The Magnuson Lab works in three areas - (i) Novel approaches to allelic series of genomic modifications in mammals, (ii)Mammalian polycomb-group complexes and development, (iii) Mammalian Swi/Snf chromatin remodeling complexes
We study genetic controls of vascular development in mouse and chick models. Current projects focus on the roles of sonic hedgehog and transcriptional silencers in control of vascular stem and progenitor cell differentiation. Other ongoing projects examine the role of notch signaling in coronary artery development, and explore the link between cytoskeletal remodeling and transcriptional activation in smooth muscle differentiation.
My research focuses on molecular mechanisms of mammalian nervous system development. We investigate mechanisms by which developing neurons migrate to the neocortex and form connections.
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.
Research in our laboratory falls at the interface between Genetics and Cell Biology and is concentrated on understanding the molecular details of how small nuclear ribonucleoprotein (snRNP) complexes are assembled and transported to their proper subcellular compartments. Interestingly, defects in the machinery required for assembly of snRNPs are associated with a neurogenetic disease called Spinal Muscular Atrophy (SMA). Mutations in the human survival of motor neurons 1 (SMN1) gene cause SMA. A variety of projects in the lab are focused on SMN's role in the biogenesis of small RNPs as well as in neuromuscular development and function. Other projects focus on nucleocytoplasmic trafficking and the functional organization of the nucleus. We use a combination of approaches, from in vitro biochemistry and cell culture, to in vivo mouse and Drosophila model systems.
My research interests include the endocrinology of pregnancy and parturition; reproductive and developmental toxicity testing; mixtures toxicology; structure-activity relationships; axial skeletal development; and strain differences in toxic responses.
Our lab investigates molecular and cellular mechanisms that regulate mammalian spermatogenesis and fertilization. A major focus of our current research is sperm energy metabolism. Our gene knockout studies demonstrate that glycolysis is essential for sperm motility and male fertility, and genomic analyses indicate that male germ cells express unique enzymes for nearly every step in this central metabolic pathway. These sperm-specific glycolytic enzymes have distinctive properties, as demonstrated by biochemical and structural analyses. Understanding how sperm energy production is regulated has significant therapeutic potential, both for the development of new contraceptive strategies and the clinical management of infertility.
Fertilization leads to the formation of a new diploid individual and represents an exquisite example of the specificity of cell to cell and cell surface-extracellular matrix interaction. Our research laboratory is interested in the study of the structure and function of sperm proteins. The long-term goal of our research is to define a set of sperm molecules that are necessary for one or more steps in the fertilization process. A full understanding of the mechanisms of sperm maturation and fertilization would allow precise targets for both infertility diagnosis and contraception.
Currently, the structure and function of two different proteins are under study. These proteins are: 1) NASP a nuclear protein that binds and transports linker histones into the nucleus and is critical for mitosis and meiosis; 2) Eppin a testis and epididymal serine protease inhibitor.
An important step in the development of tests for the diagnosis of infertility and for the development of a male gamete based contraceptive is the determination of specific protein-protein interactions that are necessary for fertilization. Characterization of these interactions will
provide sites for contraceptive development.
Mechanisms by which cells control their shape via modulation of the actin cytoskeleton. Palladin, a novel cytoskeletal protein, may be involved in organizing the actin cytoskeleton as a scaffolding protein and may contribute to changes in cell shape.
The Patterson laboratory has 4 major focuses, each of which is funded by at least one major grant. Our longest ongoing project focuses on blood vessel growth and development, and in particular how bone morphogenetic protein signaling regulates vascular development. A second ongoing project in the laboratory is to understand at a fundamental level the cellular response to proteotoxic stress. The third major focus of our laboratory studies cardiac-specific ubiquitin ligases that regulate cardiac hypertrophy and metabolism. Finally, we have begun a human translational study that takes advantage of our expertise in genomics, proteomics, and genetics to develop an integrated DNA/RNA/protein profile database of patients with heart disease.
Cell adhesion, signal transduction, and cytoskeletal regulation during embryogenesis and in cancer. We focus on the regulation of cadherin-based cell-cell adhesion, and on Wnt signaling and its regulation by the tumor suppressor APC.
The main focus of our research is to examine the molecular and cellular mechanisms that are involved in conferring neural identity to stem cells during embryogenesis and the adult.
Our sensory experiences leave indelible marks on the brain, and the Philpot Lab seeks to understand how this occurs at the level of the synapse. Our research examines the experience-dependent mechanisms that allow functional cortical circuits to emerge and for memories to be stored. We use electrophysiology, biochemistry, and genetic manipulations to study fundamental mechanisms of synaptic plasticity relevant to disease models and other neuropathologies (e.g. amblyopia, mental retardation, and schizophrenia). Through our studies in the visual cortex and hippocampus, we aim to provide insights into preventing common neuropathologies and to discover mechanisms for promoting neural regeneration in the mature brain.
Using a combination of in vivo and in vitro approaches, our lab studies the extracellular cues and intracellular signaling pathways regulating neuronal migration, axon guidance and dendritic differentiation during early aspects of brain development.
The intestine harbors a large and diverse community of microorganisms. This gut microbiota impacts upon many aspects of host biology, including nutrient metabolism, immunity, and epithelial cell renewal. Our lab is using genetic and molecular methods in gnotobiotic zebrafish hosts and in selected members of the gut microbiota, to investigate the mechanisms underlying evolutionarily-conserved host-microbial interactions in the vertebrate digestive tract.
Keywords: intestine, microbiota, bacteria, symbiosis, commensalism, immunity, inflammation, metabolism, obesity, germ-free, gnotobiotics, zebrafish
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.
.
The research in our lab is centered on understanding the mechanisms and principles of movement at the cellular level. Cytoskeletal filaments - composed of actin and microtubules - serve as a structural scaffolding that gives cells the ability to divide, crawl, and change their shape. Our lab uses a combination of cell biological, biochemical, functional genomic, and high resolution imaging techniques to study cytoskeletal dynamics and how they contribute to cellular motion.
Work in my laboratory is directed at the role of neuronal growth factors in the development and regeneration of axons. We employ sensory neurons of the DRG as a model system. Sensory neurons are unique in elaborating a peripheral axon that regenerates readily after injury and a central axon projecting in the spinal cord that does not. This work is directly relevant to a major NINDS goal of achieving spinal cord repair.
My laboratory studies development and function of the human immune system and human liver, and HIV-1/HCV infection and immuno-pathogenesis. 1. Humanized mouse models to study human hamatopoietic stem cells (HSC), thymus and liver stem cells. 2. FoxP3 and regulatory T (Treg) cells in viral infection and immuno-pathogenesis. 3. Modeling immuno-pathogenesis and immuno-therapy of chronic HIV and HCV.
Research in my laboratory is directed toward achieving a better understanding of the mechanisms and pathogenesis associated with a variety of environmentally induced or genetically based birth defects. This information is then applied to development of preventative/ameliorative measures relative to these defects. Our interest in modeling human genetic malformation syndromes and opportunities for collaborative efforts with molecular geneticists who have produced transgenic mice and mice with targeted gene modification have proven productive in our attempt to better understand the developmental basis for a variety of malformations of the brain including anencephaly, holoprosencephaly, and hydrocephaly. Regarding teratogen-induced birth defects, our major emphasis is on Fetal Alcohol Spectrum Disorders (FASD). Currently, high resolution magnetic resonance imaging (MRI) is being utilized to identify, characterize, and correlate the craniofacial, ocular, otic and CNS dysmorphology that results from prenatal ethanol exposure at specific stages of embryogenesis. These studies are designed to inform human clinical research and to expand the diagnostic criteria for prenatal alcohol exposure.
The goal of our research is to identify signaling mechanisms that contribute to normal and pathophysiological cell growth in the cardiovascular system. We study cardiac and vascular development as well as heart failure and atherosclerosis.
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 genetic pathways for the development of cardiac and vascular smooth muscle cells. In particular, the transcriptional control of mammalian cardiovascular system, and cell proliferation and differentiation-related human cardiovascular disorders.
Using genetic, cell biology, biochemical and proteomic approaches to determine the function and mechanism of - (1) CDK inhibitors in development and tumor suppression, (2) the p53 degradation and transport, and (3) RING family of ubiquitin ligases.
We employ modern technologies - genomics, proteomics, mouse models, multi-color digital imaging, etc. to study cancer mechanisms. We have made major contributions to our understanding of the tumor suppressor ARF and p53 and the oncoprotein Mdm2.
