Bath-application of DBHQ induced an outwardly-rectifying whole-cell Cl- current, which was abolished by pipette addition of BAPTA (5 mM) or CaMK [273-302] (20 microM), an inhibitory peptide of multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII). Ion channels, and ion fluxes in general, appear to regulate a wide variety of processes important to lymphocyte function in normal and disease states. She took one to Dr. Phyllis Gardner, a Stanford Medical School professor. These results favour the involvement of A2AR. CFTR involvement in cAMP regulation of Cl- conductance in lymphocytes is further supported by our demonstration of the presence of appropriately spliced CFTR mRNA segments in human B and T lymphocytes as detected by an optimized reverse-transcription and polymerase chain reaction approach. Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed. View details for Web of Science ID A1989AU52300004. Young, W., Chen, J., Jung, F., Gardner, P. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer. Gardner recently opened up about her distrust and dislike . View details for Web of Science ID A1994NA28800008, View details for Web of Science ID A1994BB86U00010. Because hearing loss is a major public health concern and common at all ages, this test is suitable for follow-up after newborn hearing screening and for the detection of a genetic etiology in older children and adults.Comprehensive and relatively inexpensive genetic testing for sensorineural hearing loss will improve medical management for affected individuals and genetic counseling for their families. 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. 4. Bay K 8644 from 10(-9) to 10(-4) M caused a dose-dependent rise in the intracellular free Ca concentration, an effect that was not mimicked by the dihydropyridine Ca antagonist nifedipine. The stimulant effect of CPCA (10 microM) was abolished by addition of the A2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) (100 microM; reported K(i) = 11 +/- 3 microM). 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. We were unable to detect a statistically significant difference between our control and affected populations regarding the frequency of sequence variants detected with the APEX array. About Dr. Phyllis Gardner. The host immune response and low vector efficiency have been key impediments to effective cystic fibrosis transmembrane regulator (CFTR) gene transfer for cystic fibrosis (CF). The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. 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. Sense and misantisense oligomers served as controls. But that's not why people are recognizing Phyllis Gardner on the street and in airports these days. These results show that Ca2+ changes are associated with the effects of rhTNF alpha and that CaM kinase plays a role in the mechanism underlying rhTNF alpha-induced activation of Ca(2+)-activated Cl- current in human neutrophils. In addition, the current was blocked by 10 microM 5-nitro-2(3-phenylpropylamino) benzoic acid (NPPB), a potent Cl- channel blocker. The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration. Schrijver, I., Kulm, M., Gardner, P. I., Pergament, E. P., Fiddler, M. B. GSK-3 phosphorylates conserved serines necessary for nuclear export, promotes nuclear exit, and thereby opposes Ca2+-calcineurin signaling. However, chronic respiratory inflammation and infection remain unexplained phenomena in disease pathogenesis. Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. View details for Web of Science ID A1994PH25400057. These results underscore the disparity in mutation identification between Caucasians and Hispanics and show utility for comprehensive diagnostic CFTR mutation analysis in this population. There is also an associated K+ efflux and membrane hyperpolarization. View details for Web of Science ID A1991GP26900012. Dr. Phyllis Gardner Despite Holmes' ability to charm older white businessman, assembling an impressive all-male board of directors at Theranos, there was one person who told her what she was. Dr. Phyllis Gardner, MD, is an Internal Medicine specialist practicing in Stanford, CA with 47 years of experience. Pyrimidine and purine nucleosides were used to assess antagonism of the antiproliferative activity of A77 1726. This page may have moved, does not exist, or we may be experiencing a temporary issue. (ABSTRACT TRUNCATED AT 400 WORDS), View details for Web of Science ID A1990DA09800009. Support teaching, research, and patient care. The Ca2+ signal can be separated into an early transient peak due to InsP3-released Ca2+ from intracellular stores, and a sustained plateau due to altered transmembrane Ca2+ flux. The hemolytic activity is associated with a 107-kDa band as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and confirmed by Western blotting and immunoprecipitation. View details for Web of Science ID A1993KN53300018. The half-life of functional CFTR is less than 24 h in these cells. The initial technical evaluation of this microarray demonstrates that it is comprehensive, robust, sensitive, specific, and easily modifiable. The site facilitates research and collaboration in academic endeavors. Amino acid differences between these isoforms and the rat brain gamma isoform (which we refer to as gamma A) are localized to the variable domain. Phyllis Gardner Professor of Medicine (Clinical Pharmacology) Medicine - Clinical Pharmacology Bio ACADEMIC APPOINTMENTS Professor, Medicine - Clinical Pharmacology Research & Scholarship CURRENT RESEARCH AND SCHOLARLY INTERESTS 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. We conclude that expression of mutant CFTR in human TCC is accompanied by ion channel dysfunction characteristic of the CF phenotype, and is accompanied by a reduction in IL-10 secretion after polyclonal activation. 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 . Significant transduction of the tissue was observed and histochemical staining was used to identify enterocytes as the primary targets of gene transfer. Maldonado, D., Schumann, M., Nghiem, P., Dong, Y., Gardner, P. REGULATION OF CL- CHANNELS BY MULTIFUNCTIONAL CAM KINASE. The universal newborn hearing screening program, together with remarkable recent progress in the characterization of genes associated with the function of hearing, have resulted in increased demand and exciting possibilities of detecting the molecular basis of hereditary hearing loss through DNA testing. In the presence of costimulation, Ca2+ influx in T cells leads to activation (transcription of interleukin-2; ref. She was 78 years old. By means of arrayed primer extension technology, we have designed a genotyping microarray with 204 probe sites for CF transmembrane conductance regulator gene mutation detection. It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines. In murine myeloma and hybridoma cells, a voltage-gated Ca2+ channel similar to Ca2+ channels in nerve, heart, and muscle is present. 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. Specific attenuation of interleukin-2 transcriptional induction occurs in Jurkat T cells following pretreatment with a Ca2+ ionophore. Academic pgardner@stanford.edu Tel: (650) 387-9319 Fax: (650) 327-9755. In the Ashkenazi Jewish population, serious and lethal genetic conditions occur with relatively high frequency. A., Messner, A. H., Moran, M. L., DAIFUKU, R., Kouyama, K., Desch, J. K., Manley, S., Norbash, A. M., Conrad, C. K., Friborg, S., Reynolds, T., Guggino, W. B., Moss, R. B., Carter, B. J., Wine, J. J., Flotte, T. R., Gardner, P. Maxillary sinusitis as a surrogate model for CF gene therapy clinical trials in patients with antrostomies. CFTR is required for the cAMP pathway but not for the calcium pathway. Encina Hall West Suite 100 Stanford, CA 94305-6044 Phone: 650-723-1806 Campus Map View details for Web of Science ID 000177015400009. Cystic fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells. View details for Web of Science ID A1991FH80200006. By use of whole cell patch-clamp and Indo-1 fluorescence studies of the Jurkat T leukaemic cell line, we show that the new organic antagonist of receptor-mediated Ca2+ entry, SK&F 96365, inhibits the T cell Ca2+ current in a dose-dependent fashion, with an IC50 of 12 microM. This cost-effective array is based on a diversely applied platform technology and is suitable for both carrier screening and disease detection in Ashkenazi and Sephardic Jewish populations. About Phyllis Gardner, M.D. The current was similarly activated by 1 microM ionomycin, a Ca2+ ionophore. Modulation of the voltage-gated K+ conductance in T-lymphocytes by substance P was examined. We demonstrate here that volume-regulated chloride-selective currents can be induced in cells with or without P-gp expression. Cystic fibrosis C1-channels in epithelial cells and lymphocytes; associated signal transduction pathways and cell biological coupling mechanisms. We are interested in the general process of signal transduction, focusing on the role that ion channels play in this process. 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. In addition, several other internal feedback controls on TCR/CD3 function, by CD4-induced tyrosine-specific phosphorylation of the CD3 zeta subunit, or on the Ca2+ signal, by extracellular Cl- or by GM1 gangliosides, are also postulated. This difference was independent of atopy. Phyllis Gardner Age: 68 Position: Professor of medicine at Stanford, board member at Revance Therapeutics and CohBar. View details for Web of Science ID 000074207900007, View details for Web of Science ID 000074088900015, View details for Web of Science ID 000073201700014. Academic pgardner@stanford.edu Tel: (650) 387-9319 Fax: (650) 327-9755 Current Research and Scholarly Interests We are interested in the general process of signal transduction, focusing on the role that ion channels play in this process. A., Gardner, P. RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR-ALPHA INDUCES CALCIUM OSCILLATION AND CALCIUM-ACTIVATED CHLORIDE CURRENT IN HUMAN NEUTROPHILS - THE ROLE OF CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE. Wagner, J. Stanford Hospital and Clinics. (Photo by Dai Sugano/MediaNews . View details for Web of Science ID A1995QV29100011. The P1 agonists tested (at 0.01 and 0.1 mM) revealed a rank order of potency of 5'-N-ethylcarboxamine adenosine (NECA) > 2-chloro-adenosine (2-Cl-ADO) > R-phenylisopropyl adenosine (R-PIA). 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. A., COZENS, A. L., Schulman, H., Gruenert, D. C., Stryer, L., Gardner, P. PATCH CLAMP STUDIES OF LYMPHOCYTE-ACTIVATION, MODULATION OF MEMBRANE K+ CONDUCTANCE IN LYMPHOCYTES-T BY SUBSTANCE-P VIA A GTP-BINDING PROTEIN, IDENTIFICATION OF A HEMOLYSIN FROM ACTINOBACILLUS-PLEUROPNEUMONIAE AND CHARACTERIZATION OF ITS CHANNEL PROPERTIES IN PLANAR PHOSPHOLIPID-BILAYERS. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. The ability of SK&F 96365 to inhibit IL-2 synthesis and cell proliferation suggests that a new class of related Ca2+ channel blockers can be developed as immunosuppressive agents. View details for Web of Science ID A1993KR82200022. View details for Web of Science ID A1988Q219900001, Department: Medicine - Med/Clinical Pharmacology, Genetic Analysis of Presbycusis by Arrayed Primer Extension. View details for DOI 10.2353/jmoldx.2007.060100, View details for Web of Science ID 000245427600013, View details for PubMedCentralID PMC1867437. You may use our global navigation in the heading bar or return to our home page using the buttons below. Hometown: Her father was a professor, so she grew up in college towns. Exclusion criteria comprised known causes of hearing loss such as significant noise exposure, trauma, ototoxic medication, neoplasm, and congenital infection or syndrome, as well as congenital or pediatric onset. The precise functional role of the voltage-activated K+ channel remains to be determined. Intracellular administration of hydrolysis-resistant guanosine triphosphate (to persistently activate GTP-binding protein) and guanosine diphosphate (to competitively inhibit GTP-binding proteins) analogues mimicked and inhibited substance P-induced reduction of K+ conductance, respectively. By use of whole-cell patch clamp recordings, we show that nitric oxide activates cystic fibrosis transmembrane conductance regulator CI- currents in normal human cloned T cells by a cGMP-dependent mechanism. B., Wagner, J. We conclude that CFTR mRNA is expressed in lymphocytes, consistent with the cAMP regulation of chloride transport present in normal lymphocytes but defective in CF-derived lymphocytes. The question of whether a G protein couples TCR/CD3 to PI hydrolysis and to Ca2+ mobilization is unresolved, although some indirect evidence for the involvement of GTP binding proteins in T cell activation has recently been obtained with cholera toxin. Whole-cell patch clamp revealed that a 48-h antisense treatment of T84 and 56FHTE-8o- fetal tracheal epithelial cells reduced the cAMP-activated chloride current to approximately 10% of that in sense-treated cells. Expression of the CFTR protein is thought to be physiologically important only in exocrine epithelial cells. DBHQ stimulated 125I efflux and mobilized intracellular free Ca2+ in a dose-dependent manner. 7. We show the cDNA structure of two variants of this human CaM kinase, gamma B and gamma C, which are predicted to translate to 518 and 495 amino acids, respectively. T-cell receptor signalling activates multifunctional CaM kinase. She sits on the Harvard Medical School Board of Fellows and the boards of biotechnology companies. In conclusion, our results suggest that A2AR participates in regulation of airway C1 secretion via aCa2+-dependent signalling pathway, which involves CaMK and appears to be at least partially conserved in cystic fibrosis airway epithelial cells. Gardner tried to. By means of path clamp recording and associated cell and molecular biological techniques, we have studied:1. Phyllis Gardner, an American biologist, was born on July 7, 1950, and is well known for being one of the first to question and challenge Elizabeth Holmes' beliefs. When transfected into Jurkat T cells, the gamma B cDNA encoded a functional kinase which cosedimented on sucrose gradients with endogenous T cell CaM kinase activity and formed a large multimeric enzyme. Elevation of internal Ca2+ inactivates the channel, whereas internal perfusion with inositol 1,3,4,5-tetrakisphosphate (InsP4) does not affect it. These findings suggest that two Ca2+/calmodulin-responsive enzymes, multifunctional CaM kinase and calcineurin, could mediate the divergent effects of Ca2+ signals in T-lymphocyte regulation. View details for Web of Science ID A1994PH77400001. 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. Site-directed mutagenesis of the predicted autoinhibitory domain yielded a mutant which was approximately 37% active in the absence of Ca2+/calmodulin, confirming the region as critical for autoregulation, and suggesting this mutant as a tool for studying the role of CaM kinase in nonneuronal tissues. 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. Phyllis Gardner. T cell clones (TCC) from controls and CF patients displayed equivalent Ca(2+)-mediated Cl- current; however, TCC from patients with CF but not controls displayed defective cAMP-mediated Cl-current. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. These sites represent the most common variants in Tay-Sachs disease, Bloom syndrome, Canavan disease, Niemann-Pick A, familial dysautonomia, torsion dystonia, mucolipidosis type IV, Fanconi anemia, Gaucher disease, factor XI deficiency, glycogen storage disease type 1a, maple syrup urine disease, nonsyndromic sensorineural hearing loss, familial Mediterranean fever, and glycogen storage disease type III. Cystic fibrosis (CF) is a common genetic disorder characterized by defective epithelial chloride transport and progressive lung disease. Gardner, P., Alcover, A., Kuno, M., Moingeon, P., Weyand, C. M., GORONZY, J., REINHERZ, E. L. DIHYDROPYRIDINE BAY K-8644 ACTIVATES LYMPHOCYTE-T CALCIUM-PERMEABLE CHANNELS. In this study, replication-defective adenoviral vectors were used to explore parameters that may be important in administering gene therapy vectors to the intestine. A., Nepomuceno, I. Holmes forged ahead anyway. A., Dong, Y. J., Gruenert, D. C., Gardner, P. ACTIVATION OF INTESTINAL CFTR CL- CHANNEL BY HEAT-STABLE ENTEROTOXIN AND GUANYLIN VIA CAMP-DEPENDENT PROTEIN-KINASE. She worked within the hospitality management industry for well over 30 years. It was 2002, and the student was a Stanford University sophomore. 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. The wider application of patch-clamp and microfluorimetry techniques to lymphocytes has helped to clarify some issues and raised many more. Many of the critical T-cell signal transducing enzymes such as phospholipase C and protein kinase C contain intrinsic Ca-binding domains, but for the most part the rise in cytoplasmic Ca is transduced by specialized Ca-binding proteins that lack catalytic domains. Dr. Gardner brings to the CohBar Board over 35 years of experience in academia, medicine, pharmacology, drug delivery systems, and biotechnology investing and governance, and has received numerous national awards and honors. Who Is Phyllis Gardner? 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. The predominant effect of Bay K 8644 on these channels was to increase the probability of channel reopening, apparently without a major effect on mean channel open-time. We used antisense oligodeoxynucleotides to CFTR to reduce the expression of CFTR in colonic and tracheal epithelial cells. Schrijver, I., Ramalingam, S., Sankaran, R., Swanson, S., Dunlop, C. L., Keiles, S., Moss, R. B., Oehlert, J., Gardner, P., Wassman, E. R., Kammesheidt, A. Dr. Phyllis Gardner, a Stanford Medical School professor, was skeptical of the Theranos founder Elizabeth Holmes early on, having rejected Holmes' idea for a patch that could deploy. Holmes wanted to build a patch that would scan the wearer for infections and release antibiotics. In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. This is a review of the application of microfabrication technologies, borrowed from the semiconductor industry, to drug delivery implants incorporating structures in the nanometer dimension. The involvement of CFTR suggests a possible cystic fibrosis heterozygote advantage against STa-induced diarrhea. 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. The Stanford Medicine Alumni Association presents Women in Medicine and Science, Phyllis Gardner - Like a Salmon Swimming Upstream Stanford Medicine Alumni Awards 2022: Marian Carlson 3. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. 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. SK&F 96365 also inhibits [3H]-thymidine incorporation and interleukin-2 (IL-2) synthesis in peripheral blood lymphocytes. When the vector was directly administered to segments of the distal ileum containing a Peyer's patch, transgene expression was approximately 10-fold higher than in segments lacking a Peyer's patch. Phyllis Gardner (6 October 1890 - 16 February 1939) was a writer, artist, and noted breeder of Irish Wolfhounds. Addition of adenosine (ADO; 0.1-1 mM) markedly increased 125I efflux rate. 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. This action was blocked by substituting Cs+ for K+ in the recording pipette and by the substance P antagonist. The effect of Ca2+ ionophore on whole-cell Cl- currents is inhibited by a specific peptide inhibitor of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase).