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Research Lab Results for proteins

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  • 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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