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Michael Wolfgang Laboratory
The Wolfgang Laboratory is interested in understanding the metabolic properties of neurons and glia at a mechanistic level in situ. Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in these pathways can lead to devastating neurological disease. Conversely, altering the metabolic properties of the nervous system can have surprisingly beneficial effects on the progression of some diseases. However, the mechanisms of these interactions are largely unknown.
We use biochemical and molecular genetic techniques to study the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. We seek to understand the neurometabolic regulation of behavior and physiology in obesity, diabetes and neurological disease.
Current areas of study include deconstructing neurometabolic pathways to understand the biochemistry of the nervous system and how these metabolic pathways impact animal beh...avior and physiology, metabolic heterogeneity and the evolution of metabolic adaptation. view more
The Robinson Lab studies the way in which mechanical stress guide and direct the behavior of cells, including when they are part of tissues, organs and organ systems.
Research in the Nathaniel Comfort Lab looks at the history of biology. Areas of particular interest include heredity and health in 20th century America, genetics, molecular biology, biomedicine, the history of recent science, oral history and interviewing.
Nicholas Zachos Lab
Researchers in the Nicholas Zachos Lab work to understand variations in protein trafficking that occur during pathophysiological conditions that cause ion and water transport that result in diarrhea. We recently identified a clathrin-independent endocytic pathway responsible for elevated intracellular calcium-mediated inhibition of NHE3 activity in intestinal epithelial cells. We use advanced imaging techniques, including confocal and multi-photon microscopy, to characterize protein trafficking of intestinal transporters. We also perform functional assays using fluorescent probes (ratiometric and non-ratiometric) to measure ion transport in cell culture models, intact intestinal tissues and human small intestinal enteroids.
The O’Rourke Lab uses an integrated approach to study the biophysics and physiology of cardiac cells in normal and diseased states.
Research in our lab has incorporated mitochondrial energetics, Ca2+ dynamics, and electrophysiology to provide tools for studying how defective function of one component of the cell can lead to catastrophic effects on whole cell and whole organ function. By understanding the links between Ca2+, electrical excitability and energy production, we hope to understand the cellular basis of cardiac arrhythmias, ischemia-reperfusion injury, and sudden death.
We use state-of-the-art techniques, including single-channel and whole-cell patch clamp, microfluorimetry, conventional and two-photon fluorescence imaging, and molecular biology to study the structure and function of single proteins to the intact muscle. Experimental results are compared with simulations of computational models in order to understand the findings in the context of the system as a whole....
Ongoing studies in our lab are focused on identifying the specific molecular targets modified by oxidative or ischemic stress and how they affect mitochondrial and whole heart function.
The motivation for all of the work is to understand
• how the molecular details of the heart cell work together to maintain function and
• how the synchronization of the parts can go wrong
Rational strategies can then be devised to correct dysfunction during the progression of disease through a comprehensive understanding of basic mechanisms.
Brian O’Rourke, PhD, is a professor in the Division of Cardiology and Vice Chair of Basic and Translational Research, Department of Medicine, at the Johns Hopkins University. view more
The Sesaki Lab is interested in the molecular mechanisms and physiological roles of mitochondrial fusion. Mitochondria are highly dynamic and control their morphology by a balance of fusion and fission. The regulation of membrane fusion and fission generates a striking diversity of mitochondrial shapes, ranging from numerous small spheres in hepatocytes to long branched tubules in myotubes. In addition to shape and number, mitochondrial fusion is critical for normal organelle function.
The Seydoux 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 activate embryonic development, polarize embryos, and distinguish between somatic and germline cells, using Caenorhabditis elegans as a model system. Our research program is divided into three areas: oocyte-to-embryo transition, embryonic polarity and soma-germline dichotomy.
The Shanthini Sockanathan Laboratory uses the developing spinal cord as our major paradigm to define the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into neurons and glia. The major focus of the lab is the study of a new family of six-transmembrane proteins (6-TM GDEs) that play key roles in regulating neuronal and glial differentiation in the spinal cord. We recently discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identifies 6-TM GDEs as the first vertebrate membrane bound GPI-cleaving enzymes that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab involves defining how the 6-TM GDEs regulate cellular signaling events that control neuronal and glial differentiation and function, with a major focus on how GDE dysfunction relates to the onset and progression of disease. To solve the...se questions, we use an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior. view less
Research in the Shigeki Watanabe Lab focuses on the cellular and molecular characterizations of rapid changes that occur during synaptic plasticity. Our team is working to determine the composition and distribution of proteins and lipids in the synapse as well as understand how the activity alters their distribution. Ultimately, we seek to discover how the misregulation of protein and lipid compositions lead to synaptic dysfunction. Our studies make use of cutting-edge electron microscopy techniques in combination with biochemical and molecular approaches.
Steven Beaudry Lab
Research in the Steven Beaudry Lab aims to better understand the cellular and molecular mechanisms behind cardiovascular disease in pregnancy. Our goal is to develop more effective treatments and improve patient outcomes.