She took one to Dr. Phyllis Gardner, a Stanford Medical School professor. Foreman, P. K., Wainwright, M. J., Alicke, B., Kovesdi, I., Wickham, T. J., Smith, J. G., Meier-Davis, S., Fix, J. Stimulation of human T-lymphocytes via either the surface T3-Ti antigen-major histocompatibility complex receptor complex or the T11 molecule results in clonal proliferation through a calcium-dependent mechanism. This finding demonstrates the potential of enterocytes to serve as heterotopic sites for the synthesis of heterologous gene products that would be secreted into the lumen of the intestinal tract or into the bloodstream. Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is a mediator of calcium signals in diverse signaling pathways. Commercially available CF carrier screening panels offer a limited panel of mutations, however, making them insufficiently sensitive for certain groups within an ethnically diverse population. This Stanford Professor Tried To Stop Elizabeth Holmes - Refinery29 Secretion of interferon-gamma, IL-2, and IL-4 was comparable in CF and control TCC after both forms of activation, while IL-5 was reduced in CF TCC following anti-CD3/phorbol myristate acetate (PMA) but not after Con A. A 48-h antisense treatment reduced the expression of CFTR protein as assayed by immunoprecipitation and autoradiography to 26% of the level in sense-treated T84 cells. Whole cell voltage clamp recordings indicate that the current is carried by a Ca(2+)-selective channel that resembles T-type voltage-gated Ca2+ channels in relative conductance of different cation species. Dr. Gardner is currently a Professor with tenure at the School of Medicine at Stanford University, where she has held several positions since she began there in 1984, including Senior Associate Dean for Education and Student Affairs. Several mutations in the selected disorders that are not prevalent per se in the Ashkenazi Jewish populations, as well pseudodeficiency alleles, are also included in the array. SIGNAL TRANSDUCTION BY T-CELL RECEPTORS - MOBILIZATION OF CA AND REGULATION OF CA-DEPENDENT EFFECTOR MOLECULES, ANTISENSE OLIGODEOXYNUCLEOTIDES TO THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR INHIBIT CAMP-ACTIVATED BUT NOT CALCIUM-ACTIVATED CHLORIDE CURRENTS. She has served on the board of directors of several public and private companies, including . Preclinical and clinical research has lead to the rapid development of a variety of vectors designed to correct the basic defect in CF, including adenovirus, adeno-associated virus, and liposomes. Modulation of the voltage-gated K+ conductance in T-lymphocytes by substance P was examined. Season 15: "Theranos CEO on Trial"--Phyllis Gardner - CNBC Phyllis Gardner Now: Where is Ex-Stanford Dean Today? Update Sequence changes were identified in 11.7% and 10% of presbycusis and control alleles, respectively. View details for Web of Science ID A1991GF80400001. Mutations in a single gene, the cystic fibrosis transmembrane conductance regulator (CFTR), are responsible for this disease. What Stanford professor Dr. Phyllis Gardner thinks about Theranos Wagner, J. In the presence of costimulation, Ca2+ influx in T cells leads to activation (transcription of interleukin-2; ref. This is supported by a comparison with other large CFTR studies. @stanford: Currently teaching. View details for Web of Science ID A1995TM55700002. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis. A77 1726, the active metabolite of leflunomide, inhibits lymphocyte proliferation in vitro. View details for Web of Science ID A1991FH80200006. Thus, lymphocytes may be an accessible source of CF tissue for study of this defect, for cloning of the chloride channel complex, and for diagnosis of the disease. Three channel types that may contribute to activation have also been described in B lymphocytes. An alternative to pulmonary testing of new CF treatments is use of the maxillary sinuses as a surrogate model of CF lung disease. These results suggest that CaM kinase mediates the Ca2+ pathway of Cl- channel activation. The wider application of patch-clamp and microfluorimetry techniques to lymphocytes has helped to clarify some issues and raised many more. Depletion of stored Ca2+ by either receptor stimulation or microsomal Ca(2+)-ATPase inhibition activated a low conductance, Ca(2+)-selective, non-voltage-activated membrane current. Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: A new approach for newborn screening follow-up. She and Rupert Brooke had, on her side at least, a passionate relationship. 300 Pasteur Dr Stanford, CA 94305. Season 15: "Theranos CEO on Trial"--Phyllis Gardner American Greed reveals fresh details about one of the most infamous alleged corporate fraud cases of the 21st century - Theranos, now back in. View details for Web of Science ID A1992HD15400067. In this article we discuss the early phases of T-cell activation with an emphasis on receptor-associated signaling molecules, mobilization of Ca, and on the possible roles of Ca in signal transduction. Addition of BAPTA (10 mM), a Ca2+ chelator, to the perfusion pipette also abolished the ADO-elicited Cl- current. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. P1 purinoceptor agonists like adenosine have been shown to stimulate Cl- transport in secretory epithelia. These assays suggest a pore diameter in the order of 2 nm. In contrast, the calcium-activated chloride current was not affected by antisense treatment. Dong, Y. J., Chen, G., Duran, G. E., Kouyama, K., Chao, A. C., Sikic, B. I., Gollapudi, S. V., Gupta, S., Gardner, P. INTERLEUKIN-2 TRANSCRIPTIONAL BLOCK BY MULTIFUNCTIONAL CA2+/CALMODULIN KINASE. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. Voltage-insensitive Ca2+ channels, Ca2+-dependent K+ channels, other downstream Ca2+ dependent effector molecules; role in cellular activation and signal transduction.2. ADO (0.1-mM) and CPCA (2 microM) both induced a marked increase in intracellular [Ca2+] ([Ca2+]i); the effect of the latter was again abolished by pretreatment of the cells with DMPX. In addition, voltage-gated K+ channels, which closely resemble the delayed rectifier K+ channel of nerve and muscle, can be classified into three subtypes, according to their voltage dependence of activation, inactivation kinetics, and pharmacological sensitivity. 'Dropout' offers little new on Elizabeth Holmes; you'll still be hooked Gardner recently. View details for Web of Science ID 000083463500002. Cystic fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells. The molecular genetic basis for the majority of these patients remains obscure, however, because of the absence of associated clinical features in approximately 70% (ie, nonsyndromic hearing loss) of patients, genetic heterogeneity, and the lack of molecular genetic tests that can evaluate a large number of mutations across multiple genes.We report on the development of a diagnostic panel with 198 mutations underlying sensorineural (mostly nonsyndromic) hearing loss. Phyllis Gardner Age: 68 Position: Professor of medicine at Stanford, board member at Revance Therapeutics and CohBar. To study the mechanism by which rhTNF alpha induced Ca(2+)-activated Cl- current, we examined the involvement of calcium/calmodulin-dependent protein kinase (CaM kinase). After surgically accessing the intestine, an E1-, E3-deleted adenoviral vector encoding beta-galactosidase (beta-Gal) was directly injected into various regions of the small and large intestine of rats and rabbits. B., Messner, A. H., Moran, M. L., Batson, E. P., DiMiceli, S., Brown, B. W., Desch, J. K., Norbash, A. M., Conrad, C. K., Guggino, W. B., Flotte, T. R., Wine, J. J., Carter, B. J., Reynolds, T. C., Moss, R. B., Gardner, P. Safety and biological efficacy of an adeno-associated virus vector cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Ca2+ influx induced by inositol 1,4,5-triphosphate (IP3)-coupled surface receptors (either the TCR or a heterologous muscarinic receptor) was compared with Ca2+ influx induced by inhibitors of the microsomal Ca(2+)-ATPase (thapsigargin, cyclopiazonic acid, di-tert-butylhydroquinone), which release stored Ca2+ without production of IP3. Phase I/II AAV-CFTR gene therapy trials.3. A., McDonald, T. V., NGHIEM, P. T., Lowe, A. W., Schulman, H., Gruenert, D. C., Stryer, L., Gardner, P. HUMAN-LYMPHOCYTES TRANSCRIBE THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE AND EXHIBIT CF-DEFECTIVE CAMP-REGULATED CHLORIDE CURRENT. A membrane-permeable cAMP analog mimicked the effect of PGE1, whereas intracellular application of a cAMP antagonist Rp-cAMP blocked the effect of PGE1. A proteinaceous hemolysin secreted by strain 4074 of serotype 1 of Actinobacillus pleuropneumoniae was purified by diafiltration and ion exchange chromatographic techniques. In T-cells, a number of important kinases, phosphatases, and cytoskeleton-modulating enzymes are functionally Ca dependent but have no Ca-binding domains and therefore must sense changes in the cytoplasmic Ca level through interactions with Ca-binding proteins. Several properties of the depletion-activated Ca2+ current suggest that it is carried by a novel type of Ca2+ channel rather than an electrogenic carrier or pump. Addition of purified catalytic subunit of cAMP-dependent protein kinase (PKA) plus ATP to the recording pipette also activated a similar current, whereas internally applied Walsh inhibitor, the synthetic peptide inhibitor of PKA, blocked the PGE1 effect. Phyllis Gardner | Stanford Medicine Lecturer in Management, Gradaute School of Business (2011 - Present) Lecturer, Department of Chemical Engineering (2009 - Present) Lecturer, Department of Chemical Engineering (2000 - 2003) Honors & Awards Fellow, American Institute of Medical and Biological Engineers (AIMBE) (2014 - Present) Member, National Academy of Engineering (2005 - Present) The patients were between ages 20 and 65 yr, with adult-onset sensorineural hearing loss of unknown etiology, and carried a clinical diagnosis of early presbycusis. View details for Web of Science ID A1995RF90000002, View details for PubMedCentralID PMC398388. In this study, we tested the feasibility of utilizing DBHQ to improve Cl- secretion via the Ca(2+)-dependent pathway, in the cystic fibrosis (CF)-derived pancreatic epithelial cell line CFPAC-1. We demonstrate that intracellular release of inositol 1,4,5-trisphosphate (InsP3), either from stimulation of transfected human muscarinic receptors or from photolytic release of caged InsP3, activates whole cell Ca2+ current in the Jurkat T cell line. Pretreatment of CFPAC-1 cells with up to 50 microM DBHQ for 6 h did not cause any detectable change in cell viability and did not significantly affect the cell proliferation rate. It has been suggested that P-glycoprotein (P-gp), an ATP-dependent transporter responsible for classical multidrug resistance, is also a volume-regulated chloride channel. A > 90% block of inducible interleukin-2 reporter gene activity was initiated by transfection of a constitutively active mutant of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase or CaM kinase II), but not by constitutive mutants of CaM kinase IV, calcineurin or protein kinase C. The block was complete six hours after kinase transfection and showed specificity for interleukin-2; there was no change in beta-actin transcription or in c-fos transcription induced by phorbol myristyl acetate, and a Rous sarcoma virus promoter was stimulated threefold. Pretreatment of monolayers of CFPAC-1 cells with DBHQ for 4-5 min significantly increased the Ca(2+)-independent or autonomous activity of CaMKII assayed in the cell homogenates. Support Lucile Packard Children's Hospital Stanford and child and maternal health. Furthermore, Cl- channels are activated in excised patches by purified CaM kinase in a fashion that mimics the effect of Ca2+ ionophore in cell-attached recordings. The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. In the absence of costimulation, Ca2+ influx results in anergy (interleukin-2 transcriptional block) through an unknown mechanism. This pathway is defective in cystic fibrosis-derived human cloned T cells. Phyllis I. Gardner (born July 7, 1950) is a Professor of Medicine at the Stanford University School of Medicine. Is CFTR also required for the calcium-dependent activation of chloride channels? Phyllis Gardner Professor of Medicine (Clinical Pharmacology) Medicine - Clinical Pharmacology Bio ACADEMIC APPOINTMENTS Professor, Medicine - Clinical Pharmacology Research & Scholarship CURRENT RESEARCH AND SCHOLARLY INTERESTS Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. STANFORD, CA - MAY 24: Stanford University professor Phyllis Gardner poses for a portrait on May 24, 2019, in Stanford, Calif. Gardner's blunt criticism of Theranos and its disgraced founder . Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed. Hereditary sensorineural hearing loss: advances in molecular genetics and mutation analysis, Genotyping microarray for the detection of more than 200 CFTR mutations in ethnically diverse populations. These agents induce Cl- secretion only in cells expressing the wild-type CFTR, indicating that this molecule is the final common effector of the signaling pathway. A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. A., McDonald, T. V., Gardner, P. STIMULATION OF CHLORIDE SECRETION BY P-1 PURINOCEPTOR AGONISTS IN CYSTIC-FIBROSIS PHENOTYPE AIRWAY EPITHELIAL-CELL LINE CFPEO-. Whether a physiological defect exists in the immune system of CF patients has remained controversial. Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis. We realize that a Troy High School year book may be hard to . Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). She trained in Internal Medicine at Massachusetts General Hospital, followed by a Chief Residency at Stanford University Hospital. Phyllis Gardner, Stanford University professor of medicine and health care venture capital firm partner, on her early suspicions about disgraced Theranos founder Elizabeth Holmes, whom she . Patch clamp studies in T and B cells have revealed the presence of several types of ion channels that apparently contribute to the ion fluxes and to the membrane potential changes associated with lymphocyte activation. Thus, DBHQ appears to enhance Cl- channel activity via a Ca(2+)-dependent mechanism involving CaMKII. Jan 18, 2022 Updated Mar 17, 2022, 5:09pm PDT Years before Theranos founder Elizabeth Holmes was prosecuted for fraud, Dr. Phyllis Gardner saw right through her. She is currently a tenured professor at the School of Medicine at Stanford University . Who Is Phyllis Gardner? The precise functional role of the voltage-activated K+ channel remains to be determined. McDonald, T. V., Premack, B. A., Goeddel, D. V., Gardner, P. PROPERTIES OF CA CURRENTS ACTIVATED BY T-CELL RECEPTOR SIGNALING, CLONING AND ANALYSIS OF 2 NEW ISOFORMS OF MULTIFUNCTIONAL CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE - EXPRESSION IN MULTIPLE HUMAN TISSUES. Expression of the CFTR protein is thought to be physiologically important only in exocrine epithelial cells. Moss, R. B., BOCIAN, R. C., Hsu, Y. P., Dong, Y. J., Kemna, M., Wei, T., Gardner, P. Mechanism of the antiproliferative action of leflunomide - A77 1726, the active metabolite of leflunomide, does not block T-cell receptor-mediated signal transduction but its antiproliferative effects are antagonized by pyrimidine nucleosides. Although great strides have been made in the treatment of CF, it remains lethal, often by early adulthood. Gardner is played by actress Laurie Metcalf in the series premiere episode of 'The Dropout.' Premack, B. The advent of universal newborn hearing screening in the United States and other countries, together with the identification of genes involved in the process of hearing, have led to an increase in both the need and opportunity for accurate molecular diagnosis of patients with hearing loss. These findings not only delineate a novel transduction mechanism for nitric oxide but also support the hypothesis that an intrinsic immune defect may exist in cystic fibrosis. Wagner, J. Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, genetic counseling, patient-specific treatment, and the understanding of cystic fibrosis (CF) pathogenesis.
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