In the Rong Li lab, we strive to understand the fundamental laws governing the behavior and interactions of cellular systems. Our current work focuses on questions pertaining to the molecular and physical basis of self-organization during morphogenesis, and the evolutionary dynamics of cell division pathways. We also work toward applying insights learned from basic research to the understanding and cure of diseases such as cancer and polycystic kidney disease. [more..]
Debbie Andrew is a geneticist and developmental biologist. She explores the regulation of form and function in epithelial tubes of fruit flies (Drosophila). Using an array of genetic tools and genome-wide transcription profiling, Debbie’s lab has revealed key regulators of epithelial tube formation and physiological specialization, providing insight into the mechanisms of epithelial tube morphogenesis and homeostasis in human development and disease. [more…]
The Lab of Mechanochemistry and Functional Imaging Applications (MAFIA) we develops multi-scale, multi-modal imaging tools to study how mechanics integrates with other biophysical and biochemical factors to sustain normal physiology or to cause pathology. [more…]
Our group studies chemotactic cell migration, the ability to sense external gradients and respond directionally. This process plays a key role in normal physiology and we believe that knowledge of this fundamental process will also lead to new therapeutic strategies for inflammatory disease and metastasis. Studies in the amoeba Dictyostelium have shown that surface chemoattractant receptors and G-proteins are not significantly clustered at the front of the cell while downstream signaling events, such as PIP₃ accumulation, are sharply localized at the cell’s leading edge. A few proteins have also been localized at the trailing edge. Many of these findings have been repeated in human and zebrafish neutrophils demonstrating the generality of the mechanisms. [more…]
Research in the Ewald laboratory starts from a simple question: which cells in a breast tumor are the most dangerous to the patient and most responsible for metastatic disease? To answer this question, we developed novel 3D culture assays to allow real-time analysis of invasion. Briefly, we use enzymatic digestion to isolate thousands of “tumor organoids” from each primary tumor. Each organoid is composed of 200-500 epithelial cancer cells and reflects the cellular heterogeneity of the primary tumor. [more…]
The Holland lab is interested in the molecular mechanisms that control accurate chromosome distribution and the role that mitotic errors play in human health and disease. Our work utilizes a combination of chemical biology, biochemistry, cell biology and genetically engineered mice to study pathways involved in mitosis and their effect on cell and organism physiology. A major focus of the group is to develop cell and animal-based models to study the role of cell division defects in genome instability and tumorigenesis. [more…]
Members of the Iglesias lab use analytic tools from control and dynamical systems to study various aspects of cell biology. Primary interests include: chemotaxis – the process by which cells sense gradients in extracellular concentrations and use this information to guide their movement; cytokinesis – the last step in the cell division in which the mother cell physically divides in two; and lipid homeostasis – where cells sense and respond to changes in their environment that affect the composition of the cell membrane. In addition to his primary appointment in Electrical and Computer Engineering, Dr. Iglesias holds a number of joint appointments throughout the university, including the Departments of Cell Biology and Biomedical Engineering at the School of Medicine, and the Department of Applied Mathematics and Statistics at the Whiting School. Dr. Iglesias, who is the Edward J. Schaefer Professor of Electrical Engineering, studied at the University of Toronto and Cambridge University, where he received his doctorate in 1991. He has had visiting appointments at Lund University, the Weizmann Institute of Science, Caltech and the Max Planck Institute for the Physics of Complex Systems.[more…]
Complexity in signaling networks is often derived from co-opting one set of molecules for multiple operations. Understanding how cells achieve such sophisticated processing using a finite set of molecules within a confined space –what we call the “signaling paradox”- is critical to biology and engineering as well as the emerging field of synthetic biology. We have recently developed a series of chemical-molecular tools that allow for inducible, quick-onset and specific perturbation of various signaling molecules. Using this novel technique in conjunction with fluorescence imaging, microfabricated devices, quantitative analysis and computational modeling, we are dissecting intricate signaling networks. In particular, we investigate positive-feedback mechanisms underlying the initiation of neutrophil chemotaxis (known as symmetry breaking), as well as spatio-temporally compartmentalized signaling of Ras and membrane lipids such as phosphoinositides. In parallel, we also try to understand how cell morphology affects biochemical pathways inside cells. Ultimately, we will generate completely orthogonal machinery in cells to achieve existing, as well as novel, cellular functions. Our synthetic, multidisciplinary approach will elucidate the signaling paradox created by nature. [more…]
The Kolodkin laboratory works to understand how neuronal connectivity is established, maintained, and modulated. Currently, the Kolodkin Lab is investigating how families of invertebrate and vertebrate guidance cues orchestrate neuronal wiring during embryogenesis and later in neural development, using Drosophila and the mouse as model systems. Alex’s team is currently investigating how laminar organization is established in the mammalian visual system, the underlying biochemical basis for guidance cue receptor responses to various guidance cues, and how classical guidance cues influence synaptogenesis and synaptic plasticity. [more…]
The human body represents an exquisite feat of bioengineering. Physical and biochemical stimuli actively regulate cell function. Our research is directed at understanding how physical cues (i.e., confinement or fluid shear stress) regulate cell responses pertinent to cancer metastasis and inflammation using physiologically relevant in vitro and in vivo models. This is accomplished through the synthesis of engineering and microtechnology principles with quantitative modeling and concepts from biophysics, biochemistry and molecular cell biology.
Some of the key research contributions by the Konstantopoulos lab are (1) the discovery of novel selectin ligands that mediate tumor cell adhesion in the vasculature, (2) the biophysical characterization of these adhesive interactions at the single-molecule level, and (3) the elucidation of novel signaling mechanisms during migration through physically confined microenvironments. Specifically, by integrating expertise in microfluidics, imaging, cell & molecular biology and mathematical modeling, we discovered a new mechanism of tumor cell migration in confined spaces that is driven by water permeation. [more…]
Using novel optical tools, our goals are to understand cell motility and the regulation of cell shape. Regulating cell shape is important for many essential functions, including immunological defense (movie). We pioneered laser-based nanotechnologies, including optical tweezers, nanotracking, and laser-tracking microrheology. Applications range from physics, pharmaceutical delivery by phagocytosis (cell & tissue engineering), bacterial pathogens important in human disease and cell division.
As Director of Imaging and Microscope Facility, I have additional research projects related to microscopy. We are developing laser-based super-resolution technology that could image fluorescent proteins with near-molecular spatial resolution within cells. However, fluorescence doesn’t reveal the subcellular environment around these key proteins. Combined with high-pressure freezing (2000 atm and freezing within 15 ms!), correlations between fluorescence and electron microscopy should provide outstanding images of subcellular structure around critical proteins. [more…]
The Meffert lab studies mechanisms underlying enduring changes in brain function. We are interested in understanding how programs of gene expression are coordinated and maintained to mediate changes in synaptic, neuronal, and cognitive function. Rather than concentrating on single genes, our research is particularly focused on understanding the upstream processes that allow neuronal stimuli to synchronously orchestrate both up and down-regulation of the many genes required to mediate changes in growth and excitation. This process of gene target specificity is implicit to the appropriate production of gene expression programs that control lasting alterations in brain function.
Our laboratory integrates multiple approaches to address the importance of gene expression in information storage at both transcriptional and post-transcriptional levels. We use animal models and techniques of molecular biology, cell biology, biochemistry, high-throughput expression analysis and bioinformatics, virology, histology, confocal imaging, electrophysiology, mouse genetics and behavior. Neuronal gene products of interest include both proteins and non-coding RNAs. [more…]
A fundamental property of living cells is their extraordinary ability to sense and respond to a changing environment. In higher eukaryotes, malfunctioning of signaling networks has many devastating consequences such as cancer, diabetes or autoimmunity. Such consequences arise from the inability of cells to properly evaluate information and cooperate. Our main focus is to understand how individual cells use signaling networks to integrate information, and eventually coordinate collective cell behaviors.
Over the last decade, increasing evidence has shown that the stochastic nature of molecular interactions is a major challenge, especially when cells transduce environmental information. Low molecule copy numbers, macromolecular crowding and picoliter volumes shape the reality of signaling networks; a reality that is often ignored by using bulk cell-population assays. My laboratory takes a single cell approach at studying how signaling networks operate dynamically. We combine 3D live cell imaging, fluorescent biosensors and optogenetics to investigate the origins and consequences of signaling dynamics at single cell level. In particular, we concentrate in analyzing individual cells in a multicellular context where collective cell behaviors lead to complex functions, such as immune response or carcinogenesis. In developing this research program we expect to understand fundamental principles of cell signaling and multicellularity, and how they impact human disease. [more…]
The central goal of our research is to discern fundamental principles of cell shape control and then to apply this knowledge to a variety of disease states. Importantly, numerous diseases, including most cancers, lung diseases such as chronic obstructive pulmonary disease (COPD), and degenerative motor neuron disease, derive a significant portion of their etiology from defects in cell mechanics. Yet, cell mechanics has really not been explored as a source of novel therapeutic targets.[more…]
Our lab studies the earliest stages of embryogenesis to understand how single-celled eggs develop into complex multicellular embryos. We focus on the choice between soma and germline, one of the first developmental decisions faced by embryos. Our goal is to identify and characterize the molecular mechanisms that polarize embryos and distinguish between somatic and germline cells. We use the nematode Caenorhabditis elegans (C. elegans) as a model system and have recently developed scalable methods for precision genome engineering in this animal. [more…]
Broadly speaking, we explore quantitative questions in cellular biomechanics in both prokaryotes and eukaryotes. We use molecular level concepts, statistical mechanics and continuum mechanics to explain diverse biological phenomena such as cell movement, cell division and biological force generation. We are also interested in biological micro-structures and the fundamental properties of soft biological materials. [more…]
For information processing and integration, neurons undergo rapid cellular and molecular reorganization. At the level of a synapse, the entire structure of the postsynaptic compartment, dendritic spines, can alter rapidly to mediate synaptic plasticity. At the molecular level, the addition of receptors to the surface of spines is associated with strengthening of synapses while their removal is associated with weakening and neurodegeneration. Many of these changes take place on a millisecond time scale. Despite the importance of these changes to the organism, remarkably little is known about either how the morphology of spines is regulated or how the surface occupancy of receptors is regulated. What are the morphological changes that trigger synaptic plasticity? How are receptors redistributed during this process? What are the molecular pathways that mediate the redistribution? We aim to answer these questions using cutting-edge electron microscopy techniques in combination with molecular and biochemical approaches. [more…]
Researchers in the Wirtz studies the biophysical properties of healthy and diseased cells, including interactions between adjacent cells and the role of cellular architecture on nuclear shape and gene expression. Cell biophysics, single molecule manipulation, intracellular particle trafficking, instrument development, tissue engineering, and nanotechnology in biology and medicine are some of his research interests. Dr. Wirtz was elected as a fellow of the American Association for the Advancement of Science for his contributions to cell micromechanics and cell adhesion. He also was distinguished for his development and application for particle tracking methods to probe the micromechanical properties of living cells in both normal conditions and disease state. [more…]
Collaborators include Sean Sun (Mechanical Engineering), Laura Wood (Pathology/Oncology), Sharon Gerecht (Chemical and Biomolecular Engineering), Konstantinos Konstantopoulos (Chemical and Biomolecular Engineering), Andrew Feinberg (Molecular Medicine), Karen Reddy (Institute for Basic Biomedical Sciences), and Jeremy Walston (Geriatric Medicine and Gerontology).
The Xiao laboratory focuses on developing novel single-molecule imaging tools in live cells to probe various dynamic aspects of cellular processes. In the past we have developed novel single-molecule gene expression reporting systems and chromosomal DNA conformation markers to probe the dynamic of gene regulation and transcription in live bacterial cells. We also pioneered the use of superresolution imaging to probe the structure, function and dynamics of the bacterial cell division machinery. Our work is at the frontier of imaging dynamic cellular processes, and has enabled new quantitative understandings of the dynamics of gene regulation and cell division. Recently we expanded our horizons by collaborating with experts of different fields to map the spatial organization of a single human cell’s genome and epigenetic markers, and to develop new single-molecule based technologies for sensitive early detection of cancer markers in blood samples. [more…]