The long-term goals of the Nano-Omic-Bio-Engineering-Lab (NOBEL) are to understand and engineer muscle function. Muscle is the primary organ system that defines our complex movements and to a degree our life and joy (“joy’s soul lies in the doing” – W. Shakespeare). Of the 3 muscle types (skeletal, cardiac, smooth), we mostly focus on skeletal muscle, which is composed of a constellation of cell types, consumes significant amounts of metabolic energy, grows and adapts its structure and function based on its environment and uniquely repairs and regenerates when damaged. Generating...
Research in the Allen Lab is broadly focused on understanding the mechanisms of growth factor and morphogen signaling in development and disease. Specifically, we study the regulation of Hedgehog signaling during embryonic and postnatal development, as well as adult tissue homeostasis, repair and regeneration. Our research employs a wide range of approaches, including mouse genetics, chicken in ovo electroporations, biochemistry, and cell biology. The long-term goal of this work is to apply insights gained from the study of HH signaling in normal contexts to the treatment of a broad...
Our lab uses optical and electrophysiological techniques to study how hormone trafficking, signaling, and release are regulated in neurosecretory cells. We investigate these processes as they relate to stress and stress transduction at the sympatho-adrenal synapse.
Our objective is to obtain a better understanding of the development and function of neurons and glia in the peripheral nervous system using human genetics, molecular and cellular biology, and zebrafish transgenesis. The major end goal of these studies is to characterize how these cell types are affected in patients with peripheral neuropathies.
Our laboratory is interested in understanding the cellular and molecular basis of the blood-brain and blood-retinal barrier and how these barriers are compromised in diseases such as diabetic retinopathy or brain tumors. The long-term goal of this research is to develop novel therapies to restore normal barrier function.
Our lab uses cellular and mouse models to study protein folding and misfolding in pancreatic beta cells (proinsulin) and thyroid epithelial cells (thyroglobulin), in order to discover new treatments for conformational diseases that affect these cells of the endocrine system. Our lab has described the cellular and molecular basis for the human disease known as Mutant INS gene-induced Diabetes of Youth, caused in most cases by expression of misfolded mutant proinsulin.
We study basic mechanisms of membrane-bound protein quality control systems. We are interested in how membrane-bound systems select substrates with a goal of identifying cellular pathways regulated by these systems. These systems are important in pathologies related to cell stress, protein misfolding, and protein misregulation. Some of the human conditions linked to these cellular defects include Parkinson’s disease, Alzheimer’s disease, and various cancers. Our longer-term goals are to understand how changing conditions in cells target substrate proteins to these integral-membrane systems...
We are interested in the basic abnormalities leading to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Using a combination of automated fluorescence microscopy, computer science, genome engineering and optogenetics we investigate RNA and protein metabolism, how deficiencies in these pathways lead to neuron loss in ALS and FTD, and how these pathways can be modified to prevent neurodegeneration.
My lab studies the mechanisms by which transcriptional enhancers control gene expression during development, using genetic, biochemical, evolutionary, and bioinformatics approaches. We focus on enhancers that are directly regulated by cell signaling pathways, including Hedgehog, Wnt, Notch, and MAPK, all of which play important roles in development and disease.
I am studying how immunotherapy such as treatment with PDL-1 and CTLA4 affects the immune profile of tumors in mice. We are interested in looking at the differences between responsive and unresponsive tumors. I am also working on the role of how ER stress and glucose deprivation modulate Stat3 activation.
Discovery of new genes for human developmental brain disorders highlights the genes essential for brain development. The disease mechanisms associated with these genes are modeled using patient induced pluripotent stem cells and mice to understand the associated molecular pathology.
Our research group aims to combine both computational and wet lab strategies to answer questions related to the transcriptional regulatory control of human genes. We believe that a complex regulatory control determines the fates of individual non-coding regulatory elements and that the integration of diverse genetic, epigenetic, and disease data is the best way to explore this control. Using innovative computational and wet lab approaches the lab both characterizes the function of these regulatory elements as well as examines the effect of genetic variation in these regions.
Utilizing a chemical-gentic approach to engineer inhibitable kinesin motor proteins s a strategy to elucidate their fundamental properties in cells
Our laboratory is interested in understanding how cells use nutrients and how excess nutrient flux, as occurs in obesity, and diabetes, triggers insulin resistance and inflammatory responses. We are also interested in how intrinsic exercise capacity and exercise training can alter metabolism. We use metabolomics profiling and other 'omics technologies to profile metabolism in animals and humans.
The Cadigan lab is interested in signal transduction and gene regulation in Drosophila and mammalian cells. Much of our research is focused on the Wnt/beta-catenin signaling pathway, but we are also exploring other pathways involved in cell specification during development and human disease.
Our research team is identifying how the promiscuous intracellular parasite Toxoplasma gondii uses autophagy to persist indefinitely in its hosts and employs cytolytic proteins to escape from infected cells. We are also developing new tools to disrupt processes required for persistence and pathogenesis to ameliorate disease.
Signal transduction pathways used by cytokine receptors and JAK tyrosine kinases; molecular actions of growth hormone; role of SH2-B adapter proteins in regulation of the cytoskeleton, gene expression and cellular differentiation and survival.
We study the communications between transcription factors that result in epigenetic modifications at super-enhancers of oncogenes. These changes drive the development of normal lymphocytes , but also the generation of cancer stem cells in childhood leukemia. By targeting specific, synthetic lethal interactions responsible for the context dependence of transcription factors in cancer, we might combat the cancer functions of transcription factors without potential adverse consequences of total inhibition.
Dr. Chinnaiyan's laboratory has focused on functional genomic,proteomic and bioinformatics approaches to study cancer for the purposesof understanding cancer biology as well as to discover clinicalbiomarkers. He and his collaborators have characterized a number ofbiomarkers of prostate cancer including AMACR, EZH2 and hepsin. AMACRis being used clinically across the country in the assessment of cancerin prostate needle biopsies.
Using optogenetics, investigate the spatiotemporal regulation of small GTPase RhoA and how it orchestrates actin cytoskeletal dynamics responsible for junctional remodeling and cytokinesis in vertebrate epithelial tissues.
Our lab is interested in the proteolytic ECM remodeling of adipose tissues in development and obesity. Using 3-D adipocyte differentiation model and a series of genetically modified mice, we aim to define a molecular mechanism that links ECM remodeling to the regulation of organ function in development and diseases.
Biology contravenes entropy, yet many biological mechanisms are sensitive to noise and thus take advantage of entropy as a generative force. Stochastic mechanisms contribute to the production of antibodies, olfactory receptor choice, and neuronal self-avoidance. The Clowney lab is interested in how non-deterministic mechanisms requiring relatively little genetic information can produce diverse molecular affinities and cellular behaviors across cells of a single ontogenetic type.
Our laboratory studies differentiation and homeostasis in complex epithelia, in health and in disease (e.g., monogenic disorders, cancer). We study these processes from the unique perspective of the keratin intermediate filament multigene family, and focus on skin epithelia. Our research activities range from the creation and validation of transgenic mouse models in vivo to biochemical and biophysical studies on purified proteins in vitro.
Our research seeks to manipulate signaling pathways in T cells to understand their behavior. We are especially interested in how T cell recognize and respond to antigen. By applying our findings in the setting of cancer we aim to develop new immunotherapy strategies.
I study the biosynthetic trafficking of G-protein-coupled receptors (GPCRs). GPCR localization to the the cell surface is critical for functional coupling to both extracellular agonists and G-protein effectors on the plasma membrane. Despite the functional importance of GPCR localization to the plasma membrane, relatively little is known about the biosynthetic trafficking of these receptors to the cell surface. I would like to understand how the trafficking of these receptors to the cell surface is regulated and how we can target receptors to the surface to increase signaling.
I am interested in developing spatial and temporally resolved proteomic techniques to study clathrin-mediated endocytosis.
Our lab concentrates on the molecular characterization of common and rare variants in genes associated with bleeding or thrombosis risk in humans. Through the study of large cohorts of human subjects, we and others have identified genetic variants associated with altered risk for disease. In our lab, we employ molecular and cellular techniques, such as mammalian cell culture, proteomic profiling, genome-wide CRISPR mediated knock-out screens, and mutagenesis libraries to functionally characterize the altered molecular genetic mechanisms contributing to disease risk.
Studying the role of the immune system in colon cancer development.
The Dressler lab utilizes genetic and biochemical approaches to understand the development of the kidney and reproductive tract. The lab has identified multiple epigenetic and cell signaling pathways that control epithelial cell lineage specification and differentiation. These pathways also contribute to chronic and acute renal disease and cancer, for which novel therapeutics are being developed.
Cells encounter starvation during stroke and heart attack, during certain stages of development, and in rapidly growing tumors. Our lab studies how membrane traffic contributes to responses to starvation and normal cell physiology.
I am interested in the use of cryo-electron microscopy to visualize proteins and then solve their structures. Using this form of microscopy is awesome because it allows me to gain insight into how specific proteins are able to interact with one another and could help with the development of drugs!