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  • Advanced Optics Lab

    Lab Website
    Principal Investigator:
    Scot Kuo, Ph.D.
    Biomedical Engineering

    The Advanced Optics Lab uses innovative optical tools, including laser-based nanotechnologies, ...to understand cell motility and the regulation of cell shape. We pioneered laser-based nanotechnologies, including optical tweezers, nanotracking, and laser-tracking microrheology. Applications range from physics, pharmaceutical delivery by phagocytosis (cell and tissue engineering), bacterial pathogens important in human disease and cell division.

    Other projects in the lab are related to microscopy, specifically combining fluorescence and electron microscopy to view images of the subcellular structure around proteins.
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    Research Areas: optics, microscopy, physics, cellular biology, imaging, nanotechnology, drugs, tissue engineering
  • Alex Kolodkin Laboratory

    Lab Website
    Principal Investigator:
    Alex Kolodkin, Ph.D.
    Neuroscience

    Research in the Alex Kolodkin Laboratory is focused on understanding how neuronal connectivity ...is established during development. Our work investigates the function of extrinsic guidance cues and their receptors on axonal guidance, dendritic morphology and synapse formation and function. We have investigated how neural circuits are formed and maintained through the action of guidance cues that include semaphorin proteins, their classical plexin and neuropilin receptors, and also novel receptors. We employ a cross-phylogenetic approach, using both invertebrate and vertebrate model systems, to understand how guidance cues regulate neuronal pathfinding, morphology and synaptogenesis. We also seek to understand how these signals are transduced to cytosolic effectors. Though broad in scope, our interrogation of the roles played by semaphorin guidance cues provides insight into the regulation of neural circuit assembly and function. Our current work includes a relatively new interest in understanding the origins of laminar organization in the central nervous system. view more

    Research Areas: central nervous system, neural circuits, neurodevelopment, neuronal connectivity, laminar organization
  • Anne Murphy Laboratory

    Principal Investigator:
    Anne Murphy, M.D.
    Medicine
    Pediatrics

    Anne Murphy’s laboratory studies cardiomyopathy and key proteins that are part of the contracti...le apparatus. The team is looking at how modifications to these proteins might affect various diseases and heart failure. She also investigates the role of genetics in pediatric heart failure associated with acute heart failure, which is sometimes attributed to myocarditis. Her laboratory has received grants from the American Heart Association, the National Institutes of Health and the Children’s Cardiomyopathy Foundation. Murphy received the Rowe Award for Cardiology Research from the Society for Pediatric Research and other awards. Her research on the molecular basis of myocardial stunning was named one of the top 10 research achievements for 1999 by the American Heart Association. view more

    Research Areas: pediatric cardiology, cardiomyopathy
  • Center for Epithelial Disorders

    Principal Investigator:
    Mark Donowitz, M.D.
    Medicine

    The Johns Hopkins Center for Epithelial Disorders focuses on research into the physiology and p...athophysiology of epithelial cells (cells that line the cavities and interior surfaces of the body) of the gastrointestinal (GI) tract, liver, pancreas and kidney. Specifically, the center’s research seeks to:

    -Understand the mechanisms regulating the activity of transport proteins (including channels) of epithelial cells
    Characterize the mechanisms by which polarity of epithelial cells are maintained
    -Investigate the mechanisms controlling transcription of epithelial-specific genes
    Understand the pathophysiological basis of GI and renal diseases that involve the preceding three components
    -The center also provides a framework for training fellows in gastroenterology and hepatology to become independent investigators.

    The center is funded primarily through individual investigator-initiated extramural research grant support from the National Institutes of Health (NIH) as well as multi-investigator grants including RO1, PO1, UO1 and R24.
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    Research Areas: gastroenterology, epithelial cells
  • Center for Research on Cardiac Intermediate Filaments

    Lab Website
    Principal Investigator:
    Giulio Agnetti, Ph.D.
    Medicine

    The CRCIF was established to foster collaborative efforts aimed at elucidating the role of inte...rmediate filaments (IFs) in the heart. Intermediate filaments constitute a class of cytoskeletal proteins in metazoan cells, however, different from actin microfilaments and tubulin microtubules, their function in cardiac cells is poorly understood. Unique from the other two components of the cytoskeleton, IFs are formed by cell type-specific proteins. Desmin is the main component of the IFs in the cardiac myocytes. We measured the consistent induction of desmin post-translational modifications (PTMs, such as phosphorylation, etc.) in various clinical and experimental models of heart failure. Therefore, one of our main focuses is to determine the contribution of desmin PTMs to the development of heart failure in different animal and clinical models.

    Active Projects:

    • Quantification of desmin PTM-forms in different forms of heart failure at the peptide level using mass spectrometry
    • Functional assessment of the role of desmin PTMs in heart failure development using single site mutagenesis and biophysical methods
    • Molecular characterization of desmin preamyloid oligomers using mass spectrometry, in vitro and in vivo imaging
    • Assessment of the diagnostic and pharmacological value of desmin PTMs in heart failure development
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    Research Areas: heart failure, intermediate filaments
  • David Graham Lab

    Principal Investigator:
    David Graham, Ph.D., M.S.
    Molecular and Comparative Pathobiology

    The David Graham Lab studies the consequences of HIV interactions with the immune system, the r...esulting pathogenesis and how to sabotage these interactions. We apply advanced technologies like mass spectrometry to dissect processes at the molecular level. We are also actively involved in cardiovascular research and studies the ways proteins are organized into functional units in different cell types of the heart.

    Major projects in our lab are organized into three major areas: (1) H/SIV pathogenesis and neuropathogenesis, (2) Cardiovascular disease, and (3) High technology development
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    Research Areas: immunology, mass spectrometry, HIV, cardiovascular, SIV, pathogenesis
  • Elizabeth M. Jaffee, M.D.

    Lab Website
    Principal Investigator:
    Elizabeth Jaffee, M.D.
    Oncology

    Current projects include:

    The evaluation of mechanisms of immune tolerance to cancer in m...ouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors.
    This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development.

    The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed .
    This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases.

    The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics.
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    Research Areas: immunology, cancer, anti-cancer drugs
  • Erika Darrah Lab

    Lab Website
    Principal Investigator:
    Erika Darrah, Ph.D.
    Medicine

    The Erika Darrah Lab is primarily interested in the mechanisms underlying the development and p...rogression of autoimmunity in rheumatoid arthritis (RA), with a particular focus on the peptidyl arginine deiminase (PAD) enzymes. We’re focused on understanding the development of PAD4-activating autoantibodies over time and how they contribute to the development of erosive disease. Studies are underway to determine if the newly discovered antibody is mimicking a naturally occurring PAD4 binding partner and to identify potentially pro-inflammatory effects of citrullinated proteins on effector cells of the immune system. view more

    Research Areas: antibodies, autoimmune diseases, peptidylarginine deiminase enzymes, rheumatoid arthritis
  • Foster Lab

    Lab Website
    Principal Investigator:
    D. Brian Foster, Ph.D., M.Sc.
    Medicine

    The Foster Lab uses the tools of protein biochemistry and proteomics to tackle fundamental prob...lems in the fields of cardiac preconditioning and heart failure. Protein networks are perturbed in heart disease in a manner that correlates only weakly with changes in mRNA transcripts. Moreover, proteomic techniques afford the systematic assessment of post-translational modifications that regulate the activity of proteins responsible for every aspect of heart function from electrical excitation to contraction and metabolism. Understanding the status of protein networks in the diseased state is, therefore, key to discovering new therapies.

    D. Brian Foster, Ph.D., is an assistant professor of medicine in the division of cardiology, and serves as Director of the Laboratory of Cardiovascular Biochemistry at the Johns Hopkins University School of Medicine.


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    Research Areas: proteomics, protein biochemistry, heart failure, cardiology, cardiac preconditioning, cardiomyopathy
  • Green Lab

    Lab Website

    Work in the Green Lab is centered on the ribosome. The overall fidelity of protein synthesis ap...pears to be limited by the action of the ribosome, which is the two-subunit macromolecular machine responsible for decoding and translating messenger RNAs (mRNAs) into protein in all organisms. Our work is divided into four general project areas. The longest-standing research area concerns the interactions of eubacterial ribosomes and release factors. The goal is to understand the mechanism of action of release factors on the ribosome. A second research area involves biochemical and structure/function studies of the miRNA pathway, particularly the mechanism of action of the Argonaute proteins and their interacting factors. A third area of work in the lab is centered around regulation of eukaryotic translation, specifically in understanding the mechanism behind various mRNA quality control pathways and the interactions of proteins therein, as well as with the ribosome. The newest area of research in the lab extends our strengths in ribosome biochemistry to characterize the translation status of the cell using the ribosome profiling. We are using this technique to better understand the role of several factors involved in eukaryotic and prokaryotic translation fidelity. view more

    Research Areas: biochemistry, genomics, ribosome, RNA
  • Haughey Lab: Neurodegenerative and Neuroinfectious Disease

    Lab Website
    Principal Investigator:
    Norman Haughey, Ph.D.
    Neurology
    Neurosurgery

    Dr. Haughey directs a disease-oriented research program that address questions in basic neurobi...ology, and clinical neurology. The primary research interests of the laboratory are:

    1. To identify biomarkers markers for neurodegenerative diseases including HIV-Associated Neurocognitive Disorders, Multiple Sclerosis, and Alzheimer’s disease. In these studies, blood and cerebral spinal fluid samples obtained from ongoing clinical studies are analyzed for metabolic profiles through a variety of biochemical, mass spectrometry and bioinformatic techniques. These biomarkers can then be used in the diagnosis of disease, as prognostic indicators to predict disease trajectory, or as surrogate markers to track the effectiveness of disease modifying interventions.
    2. To better understand how the lipid components of neuronal, and glial membranes interact with proteins to regulate signal transduction associated with differentiation, motility, inflammatory signaling, survival, and neuronal excitability.
    3. To understand how extracellular vesicles (exosomes) released from brain resident cells regulate neuronal excitability, neural network activity, and peripheral immune responses to central nervous system damage and infections.
    4. To develop small molecule therapeutics that regulate lipid metabolism as a neuroprotective and restorative strategy for neurodegenerative conditions.
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    Research Areas: multiple sclerosis, PTSD, HAND, HIV
  • Heng Zhu Lab

    Lab Website

    The Zhu lab is focused on characterizing the activities of large collection of proteins, buildi...ng signaling networks for better understanding the mechanisms of biological processes, and identifying biomarkers in human diseases and cancers. More specifically, our group is interested in analyzing protein posttranslational modifications, and identifying important components involved in transcription networks and host-pathogen interactions on the proteomics level, and biomarkers in human IBD diseases. view more

    Research Areas: inflammatory bowel disease, biomarkers, cancer
  • Intestinal Chloride Secretion

    Principal Investigator:
    Ming-Tseh Lin, M.D., Ph.D.
    Medicine

    Intestinal chloride secretion is stimulated during diarrhea. Cholera toxin is secreted by bacte...rium Vibrio cholera and is responsible for the watery diarrhea after cholera infection. Mechanistically, cholera toxin increases intracellular cyclic AMP, which subsequently activates protein kinase A and the cystic fibrosis transmembrane regulator chloride channel (CFTR).

    However, we recently identified an intestinal cAMP-Ca cross-talk signaling pathway that is initiated by elevation of intracellular cAMP and subsequently elevates intracellular Ca concentrations through the exchange protein activated by cAMP (Epac). This observation suggests that both CFTR and calcium-activated chloride channels are targets of elevated intracellular cAMP signaling molecule.

    Therefore, we are studying the role of calcium-activated Cl channels in intestinal chloride secretion under physiological conditions and during diarrhea. We are also determining whether the recently identified transmembrane protein 16 family of proteins, which are calcium-activated chloride channels, is also involved in intestinal chloride secretion in addition to the well characterized CFTR channel.

    Increased understanding of regulation of intestinal Cl secretion provides the necessary background information for the development of therapeutic drugs for the treatment of diarrhea, constipation and cystic fibrosis. The discovery that calcium-activated chloride channels are involved in intestinal chloride secretion provides additional targets for anti-diarrhea drug development.
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    Research Areas: gastroenterology, diarrhea
  • Intestinal Na/H Exchangers

    Principal Investigator:
    Ming-Tseh Lin, M.D., Ph.D.
    Medicine

    Secretory diarrhea is a leading cause of childhood morbidity and mortality in developing countr...ies. While diarrhea can be treated with oral rehydration solution (ORS), inclusion of zinc with oral ORS has been shown to reduce the duration of diarrhea. However, how zinc improves diarrhea is not known.

    It has been shown that zinc acts as an intestinal epithelial cell basolateral potassium channel blocker of cyclic AMP-mediated chloride secretion. We discovered that zinc also stimulates intestinal sodium and water absorption via the epithelial Na/H exchanger, NHE3. Zinc reverses the effect of cyclic AMP inhibition of NHE3 activity. The effect of zinc on NHE3 cannot be duplicated with other divalent metal ions. It has been well established that Na/H exchanger regulatory proteins are involved in NHE3 regulation.

    Whether these regulatory proteins are involved in zinc stimulation of NHE3 is a focus of our study. Our goal is to reveal mechanisms to explain how zinc improves diarrhea and to understand the role of zinc in salt and water homeostasis in the gut. Our study will provide a scientific basis to justify the inclusion of zinc in ORS for the treatment of secretory diarrhea.
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    Research Areas: gastroenterology, diarrhea
  • J. Marie Hardwick Laboratory

    Lab Website

    Our research is focused on understanding the basic mechanisms of programmed cell death in disea...se pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms.

    We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains.
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    Research Areas: cell death
  • Katherine Wilson Lab

    Principal Investigator:
    Katherine Wilson, Ph.D.
    Cell Biology

    Research in the Wilson Lab focuses on three components of nuclear lamina structure: lamins, LEM...-domain proteins (emerin), and BAF.

    These three proteins all bind each other directly, and are collectively required to organize and regulate chromatin, efficiently segregate chromosomes and rebuild nuclear structure after mitosis. Mutations in one or more of these proteins cause a variety of diseases including Emery-Dreifuss muscular dystrophy (EDMD), cardiomyopathy, lipodystrophy and diabetes, and accelerated aging.

    We are examining emerin's role in mechanotransduction, how emerin and lamin A are regulated, and whether misregulation contributes to disease.
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    Research Areas: cell biology, Emery-Dreifuss muscular dystrophy (EDMD), accelerated aging, chromatin, diabetes, genomics, emerin, nuclear lamina, lipodystrophy, cardiomyopathy
  • Landon King Lab

    Principal Investigator:
    Landon King, M.D.
    Medicine

    The Landon King Lab studies aquaporins water-specific membrane channel proteins. We hope to und...erstand how these proteins contribute to water homeostasis in the respiratory tract and how their expression or function may be altered in disease states. view more

    Research Areas: respiratory system, proteomics, aquaporins
  • Mark Donowitz Lab

    Lab Website
    Principal Investigator:
    Mark Donowitz, M.D.
    Medicine

    Research in the Mark Donowitz Lab is primarily focused on the development of drug therapy for d...iarrheal disorders, intestinal salt absorption and the proteins involved including their regulation, and the use of human enteroids to understand intestinal physiology and pathophysiology. We study two gene families initially recognized by this laboratory: mammalian Na/H exchangers and the subgroup of PDZ domain containing proteins present in the brush border of epithelial cells called NHERF family. A major finding is that NHE3 exists simultaneously in different sized complexes in the brush border, which change separately as part of signal transduction initiated by mimics of the digestive process. Relevance to the human intestine is being pursued using mini-human intestine made from Lgr5+ stems cells made from intestinal biopsies and measuring function via two-photon microscopy. view more

    Research Areas: gastrointestinal system, gastroenterology, pathophysiology, diarrhea, drugs, physiology
  • Mass Spectrometry Core

    Lab Website

    The Mass Spectrometry Core identifies and quantifies proteins that change expression in well-ch...aracterized protein fractions from cancerous cells or tissues. This includes identifying and quantifying changes in binding partners and post-translational modifications. Column chromatography and gel electrophoresis-based one and two-dimensional separations of protein complexes coupled to mass spectrometry are used. Techniques such as difference gel electrophoresis (DIGE), isobaric tag for relative and absolute quantitation (iTRAQ) and 18O-labeling as well as non-labeling methods (MudPit, multi-dimensional protein identification technology) are available for quantifying relative differences in protein expression and post-translational modifications. We developed methods to detect post-translational modifications such as LCMS methods to accurately determine the intact mass of proteins, selective fluorescent labeling of S-nitrosothiols (S-FLOS) to detect nitrosated cysteines in proteins, and ion mapping methods to map post-translational modifications that produce a signature mass or mass difference when the modified peptide is fragmented. view more

    Research Areas: mass spectrometry, proteomics, cancer
  • Michael Caterina Lab

    The Caterina lab is focused on dissecting mechanisms underlying acute and chronic pain sensatio...n. We use a wide range of approaches, including mouse genetics, imaging, electrophysiology, behavior, cell culture, biochemistry and neuroanatomy to tease apart the molecular and cellular contributors to pathological pain sensation. A few of the current projects in the lab focus on defining the roles of specific subpopulations of neuronal and non-neuronal cells to pain sensation, defining the role of RNA binding proteins in the development and maintenance of neuropathic pain, and understanding how rare skin diseases known as palmoplantar keratodermas lead to severe pain in the hands and feet. view more

    Research Areas: biophysics, biochemistry, proteomics, inflammation, pain
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