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    James Frank, MD

    SchoolUCSF School of Medicine
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      Research: The epithelium in the lung is at the front line protecting the inside of the body from the outside world. Problems with this barrier function of the lung epithelium are at the center of several common lung diseases. My laboratory studies how epithelial barrier function is controlled, both in health and in disease. Our goal is to develop new therapies that beneficially target the regulatory pathways controlling epithelial barrier function. Much of our work is focused on a family of proteins called claudins, particularly claudin-4 and lung-specific claudin-18. Claudins are proteins that span the cell membrane and create points of contact with adjacent cells. Individual claudins confer distinct barrier properties to an epithelium - they determine what can pass between cells. Changes in the function or regulation of these proteins may contribute to diseases like ARDS, ventilator-associated lung injury, asthma and lung fibrosis.

      Clinical: As Co-Director of the Intensive Care Unit at the San Francisco VAMC, most of my clinical work is in the ICU, where I am an attending physician. I also see outpatients in our general pulmonary clinic and direct the Pulmonary ALS Clinic, which is part of our Multidisciplinary ALS Team. In addition to patient care I am actively involved in ICU quality improvement projects and clinical education.

      Education: Teaching students, residents and fellows is always a highlight of my day. In the ICU, I coordinate our core curriculum sessions and teach workshops on critical care ultrasound. I am also actively involved in the patient simulation program at the SFVA.

      Collapse Interests
      Acute Respiratory Distress Syndrome, Mechanical Ventilation, Ventilator-associated Lung Injury, Asthma, Epithelial Barrier Function, Critical Care Ultrasound, Amyotrophic Lateral Sclerosis, Quality Improvement, Patient Simulation, Medical Education

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      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Santhosh L, Frank J. 1665: A "SHOCKING" CASE OF A LUCAS MECHANICAL CHEST COMPRESSION DEVICE DURING CARDIAC ARREST. Crit Care Med. 2016 Dec; 44(12 Suppl 1):491. PMID: 27851300.
        View in: PubMed
      2. Elicker BM, Jones KT, Naeger DM, Frank JA. Imaging of Acute Lung Injury. Radiol Clin North Am. 2016 Nov; 54(6):1119-1132. PMID: 27719979.
        View in: PubMed
      3. Sweerus K, Lachowicz-Scroggins M, Gordon E, LaFemina M, Huang X, Parikh M, Kanegai C, Fahy JV, Frank JA. Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma. J Allergy Clin Immunol. 2016 Apr 20. PMID: 27215490.
        View in: PubMed
      4. LaFemina MJ, Sutherland KM, Bentley T, Gonzales LW, Allen L, Chapin CJ, Rokkam D, Sweerus KA, Dobbs LG, Ballard PL, Frank JA. Claudin-18 deficiency results in alveolar barrier dysfunction and impaired alveologenesis in mice. Am J Respir Cell Mol Biol. 2014 Oct; 51(4):550-8. PMID: 24787463; PMCID: PMC4189483.
      5. Hirsch J, Chalkley RJ, Bentley T, Burlingame AL, Frank JA. Double impact of cigarette smoke and mechanical ventilation on the alveolar epithelial type II cell. Crit Care. 2014; 18(2):R50. PMID: 24666941; PMCID: PMC4056080.
      6. Frank JA, Matthay MA. TGF-ß and lung fluid balance in ARDS. Proc Natl Acad Sci U S A. 2014 Jan 21; 111(3):885-6. PMID: 24449829; PMCID: PMC3903208.
      7. Yang J, Wheeler SE, Velikoff M, Kleaveland KR, LaFemina MJ, Frank JA, Chapman HA, Christensen PJ, Kim KK. Activated alveolar epithelial cells initiate fibrosis through secretion of mesenchymal proteins. Am J Pathol. 2013 Nov; 183(5):1559-70. PMID: 24012677; PMCID: PMC3814683.
      8. Frank JA. Claudins and alveolar epithelial barrier function in the lung. Ann N Y Acad Sci. 2012 Jun; 1257:175-83. PMID: 22671604.
        View in: PubMed
      9. Rokkam D, Lafemina MJ, Lee JW, Matthay MA, Frank JA. Claudin-4 levels are associated with intact alveolar fluid clearance in human lungs. Am J Pathol. 2011 Sep; 179(3):1081-7. PMID: 21741940; PMCID: PMC3157178.
      10. LaFemina MJ, Rokkam D, Chandrasena A, Pan J, Bajaj A, Johnson M, Frank JA. Keratinocyte growth factor enhances barrier function without altering claudin expression in primary alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2010 Dec; 299(6):L724-34. PMID: 20833776; PMCID: PMC3006268.
      11. Wolters PJ, Wray C, Sutherland RE, Kim SS, Koff J, Mao Y, Frank JA. Neutrophil-derived IL-6 limits alveolar barrier disruption in experimental ventilator-induced lung injury. J Immunol. 2009 Jun 15; 182(12):8056-62. PMID: 19494331; PMCID: PMC2737530.
      12. Wray C, Mao Y, Pan J, Chandrasena A, Piasta F, Frank JA. Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2009 Aug; 297(2):L219-27. PMID: 19447895; PMCID: PMC2742793.
      13. Zier LS, Burack JH, Micco G, Chipman AK, Frank JA, White DB. Surrogate decision makers' responses to physicians' predictions of medical futility. Chest. 2009 Jul; 136(1):110-7. PMID: 19318665; PMCID: PMC2716715.
      14. Kim KK, Wei Y, Szekeres C, Kugler MC, Wolters PJ, Hill ML, Frank JA, Brumwell AN, Wheeler SE, Kreidberg JA, Chapman HA. Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis. J Clin Invest. 2009 Jan; 119(1):213-24. PMID: 19104148.
        View in: PubMed
      15. Briot R, Frank JA, Uchida T, Lee JW, Calfee CS, Matthay MA. Elevated levels of the receptor for advanced glycation end products, a marker of alveolar epithelial type I cell injury, predict impaired alveolar fluid clearance in isolated perfused human lungs. Chest. 2009 Feb; 135(2):269-75. PMID: 19017890; PMCID: PMC2714162.
      16. Zier LS, Burack JH, Micco G, Chipman AK, Frank JA, Luce JM, White DB. Doubt and belief in physicians' ability to prognosticate during critical illness: the perspective of surrogate decision makers. Crit Care Med. 2008 Aug; 36(8):2341-7. PMID: 18596630; PMCID: PMC2628287.
      17. Hirsch J, Niemann CU, Hansen KC, Choi S, Su X, Frank JA, Fang X, Hirose R, Theodore P, Sapru A, Burlingame AL, Matthay MA. Alterations in the proteome of pulmonary alveolar type II cells in the rat after hepatic ischemia-reperfusion. Crit Care Med. 2008 Jun; 36(6):1846-54. PMID: 18496381; PMCID: PMC2442403.
      18. Ganter MT, Roux J, Miyazawa B, Howard M, Frank JA, Su G, Sheppard D, Violette SM, Weinreb PH, Horan GS, Matthay MA, Pittet JF. Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms. Circ Res. 2008 Apr 11; 102(7):804-12. PMID: 18276918; PMCID: PMC2739091.
      19. Frank JA, Pittet JF, Wray C, Matthay MA. Protection from experimental ventilator-induced acute lung injury by IL-1 receptor blockade. Thorax. 2008 Feb; 63(2):147-53. PMID: 17901159.
        View in: PubMed
      20. Frank JA, Erle DJ. Progress toward a systems biology approach to acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2007 Aug; 293(2):L290-1. PMID: 17575007.
        View in: PubMed
      21. Hirsch J, Hansen KC, Sapru A, Frank JA, Chalkley RJ, Fang X, Trinidad JC, Baker P, Burlingame AL, Matthay MA. Impact of low and high tidal volumes on the rat alveolar epithelial type II cell proteome. Am J Respir Crit Care Med. 2007 May 15; 175(10):1006-13. PMID: 17363773; PMCID: PMC1899270.
      22. Frank JA, Briot R, Lee JW, Ishizaka A, Uchida T, Matthay MA. Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs. Am J Physiol Lung Cell Mol Physiol. 2007 Jul; 293(1):L52-9. PMID: 17351061; PMCID: PMC2764531.
      23. Frank JA, Parsons PE, Matthay MA. Pathogenetic significance of biological markers of ventilator-associated lung injury in experimental and clinical studies. Chest. 2006 Dec; 130(6):1906-14. PMID: 17167015; PMCID: PMC2764530.
      24. Su G, Hodnett M, Wu N, Atakilit A, Kosinski C, Godzich M, Huang XZ, Kim JK, Frank JA, Matthay MA, Sheppard D, Pittet JF. Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function. Am J Respir Cell Mol Biol. 2007 Mar; 36(3):377-86. PMID: 17079779; PMCID: PMC1899321.
      25. Frank JA, Wray CM, McAuley DF, Schwendener R, Matthay MA. Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2006 Dec; 291(6):L1191-8. PMID: 16877636.
        View in: PubMed
      26. Godzich M, Hodnett M, Frank JA, Su G, Pespeni M, Angel A, Howard MB, Matthay MA, Pittet JF. Activation of the stress protein response prevents the development of pulmonary edema by inhibiting VEGF cell signaling in a model of lung ischemia-reperfusion injury in rats. FASEB J. 2006 Jul; 20(9):1519-21. PMID: 16793871.
        View in: PubMed
      27. Frank JA, Matthay MA. Leukotrienes in acute lung injury: a potential therapeutic target? Am J Respir Crit Care Med. 2005 Aug 1; 172(3):261-2. PMID: 16040787; PMCID: PMC2718469.
      28. Frank JA, McAuley DF, Gutierrez JA, Daniel BM, Dobbs L, Matthay MA. Differential effects of sustained inflation recruitment maneuvers on alveolar epithelial and lung endothelial injury. Crit Care Med. 2005 Jan; 33(1):181-8; discussion 254-5. PMID: 15644667.
        View in: PubMed
      29. McAuley DF, Frank JA, Fang X, Matthay MA. Clinically relevant concentrations of beta2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury. Crit Care Med. 2004 Jul; 32(7):1470-6. PMID: 15241090.
        View in: PubMed
      30. Frank J, Roux J, Kawakatsu H, Su G, Dagenais A, Berthiaume Y, Howard M, Canessa CM, Fang X, Sheppard D, Matthay MA, Pittet JF. Transforming growth factor-beta1 decreases expression of the epithelial sodium channel alphaENaC and alveolar epithelial vectorial sodium and fluid transport via an ERK1/2-dependent mechanism. J Biol Chem. 2003 Nov 7; 278(45):43939-50. PMID: 12930837.
        View in: PubMed
      31. Frank JA, Pittet JF, Lee H, Godzich M, Matthay MA. High tidal volume ventilation induces NOS2 and impairs cAMP- dependent air space fluid clearance. Am J Physiol Lung Cell Mol Physiol. 2003 May; 284(5):L791-8. PMID: 12562562.
        View in: PubMed
      32. Frank JA, Matthay MA. Science review: mechanisms of ventilator-induced injury. Crit Care. 2003 Jun; 7(3):233-41. PMID: 12793874; PMCID: PMC270664.
      33. Frank JA, Gutierrez JA, Jones KD, Allen L, Dobbs L, Matthay MA. Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med. 2002 Jan 15; 165(2):242-9. PMID: 11790662.
        View in: PubMed
      34. Frank JA, Wang Y, Osorio O, Matthay MA. Beta-adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats. J Appl Physiol (1985). 2000 Oct; 89(4):1255-65. PMID: 11007557.
        View in: PubMed
      35. Matthay MA, Fukuda N, Frank J, Kallet R, Daniel B, Sakuma T. Alveolar epithelial barrier. Role in lung fluid balance in clinical lung injury. Clin Chest Med. 2000 Sep; 21(3):477-90. PMID: 11019721.
        View in: PubMed
      36. Frank JA, Nuckton TJ, Matthay MA. Diabetes mellitus: a negative predictor for the development of acute respiratory distress syndrome from septic shock. Crit Care Med. 2000 Jul; 28(7):2645-6. PMID: 10921610.
        View in: PubMed
      37. Stulbarg MS, Frank JA. Obstructive pulmonary disease. The clinician's perspective. Radiol Clin North Am. 1998 Jan; 36(1):1-13. PMID: 9465865.
        View in: PubMed
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