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.
Molecular and cellular studies of auditory system development and regeneration in the mouse (including transgenic approaches), chick, zebrafish and immortalized inner ear cell lines. Studies of hormonal regulation of the tumor suppressor gene, neurofibromatosis I, using embryonic mouse stem cell approaches. Microfluidic organ cultures of inner ears and zebrafish for studies of morphogenesis.
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.
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.
Our lab is interested in the study of the tumor vascular niche; this includes tumor vascular cells, tumor stem cells and mesenchymal stem cells. We are studying both the basic biology and developing therapeutics to disrupt the vascular niche and thereby inhibit the growth of tumor stem 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.
We use genomic approaches to find and characterize genes involved in behavioral, neurological and psychiatric diseases, especially ataxia, depression and drug abuse. We follow their effects in culture on neurons differentiated from induced pluripotent stem cells from patients, and in animal models.
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.
We are broadly interested in the cell biology of T lymphocyte (T cell) function. These immune cells are central to cell-mediated immunity to infections and cancers. My laboratory uses high-resolution imaging approaches (including TIRFM, 3D super-resolution fluorescence microscopy, and transmission electron microscopy) to understand the molecular and subcellular mechanism by which T cells recognize and respond to pathogenic threats.
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.
We are focused on unraveling the pathogenesis of Parkinson's disease and dystonia. Our studies are focused on disease genes that cause these disorders, employing a range of molecular, cellular, and whole animal studies to dissect the normal role of disease proteins, and how pathogenic mutations lead to disease.
My laboratory studies disease mechanisms in cardiomyopathies with a major area of focus on regulation of the ubiquitin proteasome system in protein turnover and degradation. We are exploring the interaction between inflammation, proteasome dysfunction and ventricular remodeling in the heart. We are also interested in disease pathways triggered by sarcomere mutations in hypertrophic cardiomyopathy and understanding the interactions of the mutant allele product with RNA and protein surveillance systems.
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.
Our laboratory is interested in molecular mechanisms controlling epidermal growth and differentiation, including how this process is linked to host defense and autoimmunity. For this purpose, we utilize cell biology, organ culture, transgenic animals, genetic linkage analysis, and gene expression profiling.
Our lab exploits mouse genetics to explore the molecular basis of human disease. We are examining the consequences of targeted loss of function (traditional and conditional knockouts) and gain of function (conventional and BAC transgenics) to understand the developmental regulation of several transcription factors we have cloned over the years (GATA-2, GATA-3, small Mafs and the TR2 and TR4 orphan nuclear receptors), and to unravel their distinct contributions organogenesis.
Our research focuses on studying retinal diseases and their mechanisms, in order to develop new treatments to prevent or reverse associated vision loss. A major focus in our lab is the development of strategies to treat retinal neurodegenerations, including diabetic retinopathy. One of our objectives is to investigate the function and regulation of crystallin proteins in the adaptive responses of retinal cells during chronic disease states such as diabetes.