Finally, a Ca2(+)-activated K+ channel in T cells has recently been described. Wagner, J. This action was blocked by substituting Cs+ for K+ in the recording pipette and by the substance P antagonist. A proteinaceous hemolysin secreted by strain 4074 of serotype 1 of Actinobacillus pleuropneumoniae was purified by diafiltration and ion exchange chromatographic techniques. Cystic fibrosis (CF) is a common genetic disorder characterized by defective epithelial chloride transport and progressive lung disease. The site facilitates research and collaboration in academic endeavors. 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). Season 15: "Theranos CEO on Trial"--Phyllis Gardner - CNBC Sinusitis recurred at a rate of 45% during one month of follow-up. 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. P1 purinoceptor agonists like adenosine have been shown to stimulate Cl- transport in secretory epithelia. The transcription factor NF-AT responds to Ca2+-calcineurin signals by translocating to the nucleus, where it participates in the activation of early immune response genes. 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) Stanford Professor Phyllis Gardner on Theranos and Elizabeth Holmes This pathway is defective in cystic fibrosis-derived human cloned T cells. MiMedx Announces Appointment of Phyllis Gardner, M.D. to Stanford's Phyllis Gardner Says She Knew Elizabeth Holmes Was A Fraud Holmes forged ahead anyway. Specialties. True Story Behind The Dropout, Elizabeth Holmes | Time Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is a mediator of calcium signals in diverse signaling pathways. She sits on the Harvard Medical School Board of Fellows and the boards of biotechnology companies. 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. Since there is a significant increase in phosphoinositide turnover after stimulation via either the T3-Ti or T11 pathway, it is suggested that triggering of either structure opens a common set of channels through this mechanism. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. Among the presbycusis group, these solely occurred within the GJB2 and SLC26A4 genes. Although CF-derived TCC preserved mitogen and antigen proliferative responses and specificity to tetanus toxoid epitopes, they selectively secreted approximately 45% less IL-10 compared with control TCC after activation with concanavalin A (Con A) (624 +/- 101 versus 1564 +/- 401 pg/ml per 10(6) cells, respectively; P = 0.04) or anti-CD3/phorbol ester (5148 +/- 1634 versus 11788 +/- 2390 pg/ml; P = 0.05). Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. A similar order of potency was seen in transformed cystic fibrosis nasal polyp cells, CFNPEo- (ADO > ATP > AMP > ADP). Hometown: Her father was a professor, so she grew up in college towns. This difference was independent of atopy. Nishimoto, I., Wagner, J. A., Schulman, H., Gardner, P. ACTIVATION OF CHLORIDE CHANNELS IN NORMAL AND CYSTIC-FIBROSIS AIRWAY EPITHELIAL-CELLS BY MULTIFUNCTIONAL CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE. In contrast, the calcium-activated chloride current was not affected by antisense treatment. View details for Web of Science ID A1989T048300039. 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. Phyllis Stanko Obituary (1943 - 2021) - Fullerton, CA - Orange County A., Reynolds, T., Moran, M. L., Moss, R. B., Wine, J. J., Flotte, T. R., Gardner, P. A phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients with cystic fibrosis. View details for Web of Science ID A1997WQ51300045. Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. DBHQ stimulated 125I efflux and mobilized intracellular free Ca2+ in a dose-dependent manner. Gardner was one of the first people to be publicly skeptical of Elizabeth Holmes, the founder of blood testing company Theranos, who was later found guilty of investor fraud. Holmes wanted to build a patch that would scan the wearer for infections and release antibiotics. Thus, DBHQ appears to enhance Cl- channel activity via a Ca(2+)-dependent mechanism involving CaMKII. Michael Kovac // Getty Images Stanford professor Phyllis Gardner, MD, has been an outspoken skeptic of Elizabeth Holmes, and her now defunct company Theranos for years. Phyllis I. Gardner (born July 7, 1950) is a Professor of Medicine at the Stanford University School of Medicine. Learn how we are healing patients through science & compassion, Stanford team stimulates neurons to induce particular perceptions in mice's minds, Students from far and near begin medical studies at Stanford. These results suggest that there is no relationship between P-gp and the chloride channel activated by cell swelling. McDonald, T. V., Premack, B. . Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: A new approach for newborn screening follow-up. 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. Stanford Hospital and Clinics. 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. Gardner and. 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. For comprehensive carrier screening and molecular diagnostic purposes, we developed a population-specific and inclusive microarray. Phyllis I. Gardner, MD Director Dr. Phyllis Gardner has over 40 years of experience in academia, medicine and the healthcare industry. @stanford: Currently teaching. View details for Web of Science ID 000074207900007, View details for Web of Science ID 000074088900015, View details for Web of Science ID 000073201700014. DBHQ is a commercially available non-toxic synthetic compound chemically unrelated to THG and CPA. Phyllis Gardner Age: 68 Position: Professor of medicine at Stanford, board member at Revance Therapeutics and CohBar. Homozygous and compound heterozygous pathogenic mutations were exclusively seen in affected individuals. She was 78 years old. 2. Dr. Phyllis Gardner, MD, Internal Medicine | Stanford, CA - WebMD 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 mechanism of TCR-stimulated Ca2+ influx was studied in the Jurkat human T cell line using Ca2+ indicator dyes and whole-cell patch clamp. The effects of purinoceptor agonists on Cl- secretion were examined in a transformed cystic fibrosis airway phenotype epithelial cell line, CFPEo-. 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. A membrane-permeable cAMP analog mimicked the effect of PGE1, whereas intracellular application of a cAMP antagonist Rp-cAMP blocked the effect of PGE1. Using CF sinusitis as a surrogate model for testing clinical efficacy of new treatments is attractive because CF upper respiratory disease is similar to the lower respiratory disease with respect to electrophysiology and microbiology.Sinusitis recurrence in untreated sinuses was analyzed during a prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of the adeno-associated virus mediated cystic fibrosis transmembrane conductance regulator (AAV-CFTR) gene transfer.Clinical symptoms combined with sinus endoscopy proved useful in the diagnosis of unilateral and bilateral sinusitis recurrence. Patch-clamp studies have identified a cAMP-dependent Cl- conductance in lymphocytes that is defectively regulated in cystic fibrosis. A prospective, randomized, double-blind, placebo-controlled, within-subjects, phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF. AVESTRIA VENTURES-Phyllis Gardner 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. 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. A., Nepomuceno, I. 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. What Stanford professor Dr. Phyllis Gardner thinks about Theranos They said it: On Theranos founder Elizabeth Holmes - The Mercury News Dr. Phyllis I. Gardner is an internist in Stanford, California. 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 particular, the steady-state rise in interleukin-2 (T-cell growth factor) mRNA is dependent on the rise of [Ca2+]i resulting from ion movement across this channel. We report here that normal human B-lymphoblasts display whole cell Cl- conductances induced by calcium-mediated pathways, volume regulation, and cAMP which are equivalent to currents described in epithelial cells. We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. A prolonged (at least 2-4 hr) elevation of [Ca2+]i accompanies early T cell activation by TCR/CD3-specific ligands. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis. SCHUMANN, M. A., Gardner, P., Raffin, T. A. 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. Chao, A. C., ZIFFERBLATT, J. View details for Web of Science ID A1994PH77400001. Dr. Phyllis Gardner, MD is a board certified internist in Stanford, California. 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. When she told her professor Dr Phyllis Gardner about her idea, Gardner told her it was ambitious . The Sunday Times' tech correspondent brings on Dr Phyllis Gardner, the Standord medical professor who came across Elizabeth Holmes before she started Theranos and then worked behind the scenes to expose her, to talk about her background at Stanford (4:00), and in industry (5:00), meeting a young Elizabeth Holmes (6:55), rejecting her first idea 5. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways. View details for Web of Science ID A1994NA28800008, View details for Web of Science ID A1994BB86U00010. Photolytic release of caged 1-(alpha-glycerophosphoryl)-inositol 4,5-bisphosphate, an analog of InsP3 which activates InsP3 receptors but is not readily metabolized to InsP4, also activates the current. 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. 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). Various potentially confounding factors are discussed. The identity of the amplified products was confirmed by hybridization to CFTR-specific probes and DNA sequencing. 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. It is possible that disruption of IL-10-mediated anti-inflammatory homeostasis may contribute to early onset sustained inflammation in CF airways. View details for Web of Science ID 000231054600008. This discrepancy is even more pronounced when such carrier screening panels are used for diagnostic purposes. 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). View details for Web of Science ID 000078432500017. Sense and misantisense oligomers served as controls. In addition, the current was blocked by 10 microM 5-nitro-2(3-phenylpropylamino) benzoic acid (NPPB), a potent Cl- channel blocker. Dr. Gardner has spent more than 35 years in academia, medicine and industry. After more than a decade in conceptualisation and experimentation, four systems that have commercial potential are discussed: i) implantable microchips with on-demand microdosage for one or more therapeutic agents under internal control or external control using a wireless link; ii) nanopore pumps, implantable titanium pumps, consisting of a drug reservoir with a nanopore-release membrane, capable of delivering potent small or macromolecules at constant serum levels for sustained periods of time; iii) nanocages, microfabricated nanopore immunoisolation chambers for cellular implants, capable of natural feedback-controlled delivery of proteins and peptides; and iv) nanobuckets, micromachined silicon porous particles with drug-loading capacity and targeting ligands for localised delivery. 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. Phyllis Gardner's Profile | Stanford Profiles Wagner, J. Photos from After the Downfall: What Elizabeth Holmes and the Theranos 2) via calcineurin. The conductance saturated when external Ca2+ was raised (Kd approximately 2 mM) and became highly permeable to monovalent cations when external Ca2+ was lowered to below 100 nM, much as has been observed for some voltage-gated Ca2+ channels. View details for Web of Science ID 000228736900018. tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. In the present study, we investigated whether P1 agonist-induced Cl- secretion is preserved in cystic fibrosis airway epithelium and which signalling mechanism is involved. A group of 257 self-identified Hispanics with clinical manifestations consistent with CF were studied by temporal temperature gradient electrophoresis and/or DNA sequencing. To investigate this signal transduction, plasma membrane calcium-permeable channels were characterized in T-lymphocytes by means of whole cell or single channel patch-clamp recordings. Expression of the CFTR protein is thought to be physiologically important only in exocrine epithelial cells. 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. Phyllis Gardner Professor of Medicine (Clinical Pharmacology) Medicine - Clinical Pharmacology Bio ACADEMIC APPOINTMENTS Professor, Medicine - Clinical Pharmacology Research & Scholarship CURRENT RESEARCH AND SCHOLARLY INTERESTS She's a professor of medicine at Stanford and a former partner in a health care venture capital firm. The results suggest that the dihydropyridine Ca agonist Bay K 8644 interacts with both voltage-gated and receptor-operated Ca channels and also suggest potential strategies for development of a new class of immunomodulatory drugs. New patients are welcome. Furthermore, currents flowing through Ca2+-permeable channels are apparently autoregulated, as inward conductance is abolished by elevation of Ca2+ concentration in the bathing solution. Academic pgardner@stanford.edu Tel: (650) 387-9319 Fax: (650) 327-9755. @Stanford #PhyllisGardner was a skeptic of #ElizabethHolmes from the time she met Holmes . The maximal effects were seen at concentrations of 25-50 microM. She attended the Slade School of Fine Art and was a suffragette when they met. But that's not why people are recognizing Phyllis Gardner on the street and in airports these days. 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. In patch-clamp experiments, ADO (1 mM) induced an outwardly-rectified whole-cell Cl- current (baseline, 2.5 +/- 0.8 pA pF-1, + ADO, 78.4 +/- 23.8 pA pF-1; P < 0.02), which was largely inhibited in cells internally perfused with a selective inhibitory peptide of the multifunctional Ca2+/calmodulin-dependent protein kinase, CaMK [273-302] (20 microM), as compared to a control peptide, CaMK [284-302]. A luciferase assay quantitated interleukin-2 gene promoter activity in stimulated cells transfected with an interleukin-2 promoter-luciferase gene construct. The involvement of CFTR suggests a possible cystic fibrosis heterozygote advantage against STa-induced diarrhea. Phyllis Gardner (pictured), a professor of medicine at Stanford, criticized Elizabeth Holmes' blood testing company long before fraud charges were brought against her. DBHQ (25 microM) caused a short-term rise in [Ca2+]i in the absence of ambient Ca2+, and a sustained elevation of [Ca2+]i in cell monolayers bathed in the efflux solution (1.2 mM Ca2+), which was largely attenuated by Ni2+ (5 mM). 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. She saw through Elizabeth Holmes. Now Stanford professor is star in 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. 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. 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. 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. View details for Web of Science ID A1989AU52300004. Phyllis Gardner. Cystic fibrosis (CF), which is due to mutations in the cystic fibrosis transmembrane conductance regulator gene, is a common life-shortening disease. NFAT mediated gene transcription; modulations by kinases and phosphatases. 6. In this review, we discuss agents that increase Cl- secretion via preserved Cl- secretory pathways, such as uridine triphosphate, or that enhance Na+ resorption, such as amiloride, thereby correcting altered airway secretions. B., Shah, N., Messner, A. H., Moran, M. L., Norbash, A. M., Moss, R. B., Wine, J. J., Gardner, P. Adenovirus-mediated transduction of intestinal cells in vivo. Nghiem, P., SAATI, S. M., Martens, C. L., Gardner, P., Schulman, H. FLASH-PHOTOLYSIS OF CAGED INOSITOL 1,4,5-TRISPHOSPHATE ACTIVATES PLASMA-MEMBRANE CALCIUM CURRENT IN HUMAN T-CELLS. Dr. Phyllis Gardner, MD is an Internal Medicine Specialist in Stanford, CA and has over 47 years of experience in the medical field. When external and internal Cl- were about equal, the current reversed at about zero mV, but when external Cl- was lowered from 157 to 7 mM the reversal potential shifted 75 mV in the positive direction, demonstrating that the current carrier was Cl-. Theranos: Stanford prof never trusted Elizabeth Holmes - The Mercury News 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. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). 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. Calcineurin dephosphorylates conserved serine residues in the amino terminus of NF-AT, resulting in nuclear import. While the function of nitric oxide as a direct cytotoxic effector molecule is well established, its function as a transducer molecule in immune cells is not. Recent national guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for CF carrier status for purposes of genetic counseling. She worked within the hospitality management industry for well over 30 years. Traditional therapeutic modalities address these problems with pancreatic enzyme replacement, vitamins and nutritional supplementation, antibiotics, and respiratory therapy. Non-transformed, antigen-responsive CD4+ T cells cloned from healthy controls and CF patients homozygous or heterozygous for the delta F508 mutation transcribed CFTR mRNA and expressed immunoreactive cytoplasmic CFTR protein. 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. View details for Web of Science ID A1994NH08400029. CF is one of the most extensively researched genetic diseases as a target for gene therapy development. A., McDonald, T. V., Gardner, P. STIMULATION OF CHLORIDE SECRETION BY P-1 PURINOCEPTOR AGONISTS IN CYSTIC-FIBROSIS PHENOTYPE AIRWAY EPITHELIAL-CELL LINE CFPEO-. 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.

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