Research Summary

Dr. Lazarus is an inbred product of the University of California, having received his A.B. from Berkeley, his M.D. from Irvine, and training in Internal Medicine and Pulmonary & Critical Care Medicine at UCSF. Drafted into military service during the Viet Nam era, he spent 2 years as Chief of Pulmonary Medicine and Co-Director of the ICU at Andrews Air Force Base in Washington, D.C. before returning to UCSF for additional research training in the Cardiovascular Research Institute. Since joining the faculty at UCSF in 1983, Dr. Lazarus has directed basic and clinical research on the mechanisms and treatment of asthma, COPD, and other airway diseases. He is an Attending Physician on the Pulmonary Consult Service, the Adult Pulmonary Function Laboratory, and the Chest Faculty Practice at UCSF-Moffitt-Long Hospital, and has been Director of the Chest Faculty Practice, Director of the Medical Specialty Practices, and Interim Chief of the Division of Pulmonary and Critical Care Medicine. Currently he is Director of the Training Program in Pulmonary and Critical Care Medicine and Associate Director of the Adult Pulmonary Laboratory.

Research Interests:
Dr. Lazarus' research has focused on the role of inflammatory cells and mediators in regulating function of the lung and airways in obstructive lung diseases. After working in whole animals and organ systems, he developed continuous mastocytoma cell lines that share many important features of normal human mast cells. These cells served as a unique model system for mast cell biology as well as a source of mast cell-derived mediators to examine the role of these mediators in important biological processes.

Studies of mast cell mediators led to a series of investigator-initiated clinical research projects to examine the role of leukotrienes in chronic asthma and in mediating the bronchoconstrictor response to inhaled sulfur dioxide; the role of tachykinins in mediating the airway hyperresponsiveness, airway inflammation, and symptoms of chronic asthma; and the correlation between elastase and elastolytic activity in the sputum of patients with chronic bronchitis and physiological measures of lung function. In collaboration with Drs John Fahy, George Caughey, and Jay Nadel, Dr. Lazarus examined the effect of sputum proteases on airway inflammation, and the effect of inflammatory mediators on regulation of airway mucin gene expression and mucin secretion (via the EGF-receptor).

These studies provided the infrastructure for several successful competitive applications to the NIH to participate in Clinical Research Networks. In 1993, Drs. Boushey, Lazarus, and Fahy were awarded one of 6 Asthma Clinical Research Network (ACRN) Centers in the US, and their application was again successful in an open competition in 2003. This network conducts multicenter clinical trials to examine important mechanisms in the treatment and pathogenesis of asthma. In addition to serving on the Steering Committee of the Network, responsible for the design and implementation of all studies, Dr. Lazarus was the Lead Investigator on 2 major ACRN projects: one, a study that examined clinical outcomes and inflammatory biomarkers in subjects treated with inhaled corticosteroids or a long-acting ß-agonist, was published in JAMA, and was responsible for a change in asthma management guidelines. Dr. Lazarus also led a study that demonstrated that asthmatics who smoke have a blunted response to inhaled corticosteroids – apparently because smoking regulates transcription factors related to airway inflammation.

In 2003, Dr. Lazarus built upon studies of mucus hypersecretion and airway function to prepare a successful application to the NIH/NHLBI to participate as one of 7 sites in the COPD Clinical Research Network (CCRN). As Principal Investigator of this award, Dr. Lazarus led studies to examine biomarkers as predictors of COPD exacerbations, and to explore the role of arachidonic acid metabolites in the pathogenesis of COPD exacerbations. Dr. Lazarus Chairs the Steering Committee of this Network.

Dr. Lazarus is also Co-PI of the new (in 2009) AsthmaNet, an NHLBI network funded for 7 years to examine clinical outcomes and mechanisms of asthma. He is the lead investigator of a study of TH2 high vs TH2 low asthma phenotypes, to be launched in 2012.

Finally, in collaboration with Prescott Woodruff, Dr. Lazarus is a Co-Investigator of the new SPIROMICS network, an NHLBI-sponsored project to identify subpopulations of COPD patients that are similar with respect to molecular mechanisms of disease.

Research Funding

  • September 30, 2015 - September 30, 2021 - Beta Blockers for the Prevention of Acute Exacerbations of Asthma , Co-Principal Investigator . Sponsor: DOD Congressionally Directed Medical Research Program, Sponsor Award ID: PR140170
  • March 15, 2017 - July 31, 2021 - Losartan Effects on Emphysema Progression Trial (LEEP) , Principal Investigator . Sponsor: American Lung Association/NIH/NHLBI, Sponsor Award ID:
  • September 1, 2016 - July 31, 2021 - Carbohydrate-based Therapy for Lung Disease , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01HL128191
  • July 1, 2016 - June 30, 2021 - American Lung Association - Airways Clinical Research Centers (ACRC) Network , Principal Investigator . Sponsor: American Lung Association, Sponsor Award ID:

Education

Fellowship, 06/1977 - Pulmonary & Critical Care, University of California, San Francisco
Residency, 06/1975 - Internal Medicine, University of California, San Francisco
MD, 06/1972 - Medicine, University of California, Irvine
A.B., 06/1968 - Zoology, University of California, Berkeley

Selected Publications

  1. Wise RA, Holbrook JT, Brown RH, Criner GJ, Dransfield MT, He J, Henderson RJ, Kaminsky DA, Kaner RJ, Lazarus SC, Make BJ, McCormack MC, Neptune ER, Que LG, American Lung Association Airways Clinical Research Centers and Pulmonary Trials Cooperative. Clinical Trial of Losartan for Pulmonary Emphysema: Pulmonary Trials Cooperative LEEP Trial. Am J Respir Crit Care Med. 2022 Jun 01.  View on PubMed
  2. Parekh TM, Helgeson ES, Connett J, Voelker H, Ling SX, Lazarus SC, Bhatt SP, MacDonald DM, Mkorombindo T, Kunisaki KM, Fortis S, Kaminsky D, Dransfield MT. Lung Function and the Risk of Exacerbation in the BLOCK COPD Trial. Ann Am Thorac Soc. 2022 Apr 01.  View on PubMed
  3. Krishnan JA, Lazarus SC, Blake KV, Sorkness CA, Covar R, Dyer AM, Lang JE, Lugogo NL, Mauger DT, Wechsler ME, Wenzel SE, Cardet JC, Castro M, Israel E, Phipatanakul W, King TS. Biomarkers to Predict Response to Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists in Adolescents and Adults with Mild Persistent Asthma. Ann Am Thorac Soc. 2022 03; 19(3):372-380.  View on PubMed
  4. Hernández Cordero AI, Yang CX, Li X, Milne S, Chen V, Hollander Z, Ng R, Criner GJ, Woodruff PG, Lazarus SC, Connett JE, Han MK, Martinez FJ, Reed RM, Man SFP, Leung JM, Sin DD. Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease. Respir Res. 2021 Dec 22; 22(1):316.  View on PubMed
  5. Ortega VE, Daya M, Szefler SJ, Bleecker ER, Chinchilli VM, Phipatanakul W, Mauger D, Martinez FD, Herrera-Luis E, Pino-Yanes M, Hawkins GA, Ampleford EJ, Kunselman SJ, Cox C, Bacharier LB, Cabana MD, Cardet JC, Castro M, Denlinger LC, Eng C, Fitzpatrick AM, Holguin F, Hu D, Jackson DJ, Jarjour N, Kraft M, Krishnan JA, Lazarus SC, Lemanske RF, Lima JJ, Lugogo N, Mak A, Moore WC, Naureckas ET, Peters SP, Pongracic JA, Sajuthi SP, Seibold MA, Smith LJ, Solway J, Sorkness CA, Wenzel S, White SR, Burchard EG, Barnes K, Meyers DA, Israel E, Wechsler ME, NHLBI AsthmaNet. Pharmacogenetic studies of long-acting beta agonist and inhaled corticosteroid responsiveness in randomised controlled trials of individuals of African descent with asthma. Lancet Child Adolesc Health. 2021 12; 5(12):862-872.  View on PubMed
  6. Burkes RM, Couper DJ, Barjaktarevic IZ, Cooper CB, Labaki WW, Han MK, Woodruff PG, Lazarus SC, Parekh TM, Paine R, Comellas AP, Bowler RP, Loehr LR, Putcha N, Wise RA, Brown TT, Drummond MB. Age-Dependent Associations Between 25-Hydroxy Vitamin D Levels and COPD Symptoms: Analysis of SPIROMICS. Chronic Obstr Pulm Dis. 2021 Apr 27; 8(2):277-291.  View on PubMed
  7. Dunican EM, Elicker BM, Henry T, Gierada DS, Schiebler ML, Anderson W, Barjaktarevic I, Barr RG, Bleecker ER, Boucher RC, Bowler R, Christenson SA, Comellas A, Cooper CB, Couper D, Criner GJ, Dransfield M, Doerschuk CM, Drummond MB, Hansel NN, Han MK, Hastie AT, Hoffman EA, Krishnan JA, Lazarus SC, Martinez FJ, McCulloch CE, O'Neal WK, Ortega VE, Paine R, Peters S, Schroeder JD, Woodruff PG, Fahy JV. Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers. Am J Respir Crit Care Med. 2021 04 15; 203(8):957-968.  View on PubMed
  8. Clougherty JE, Kinnee EJ, Cardet JC, Mauger D, Bacharier L, Beigelman A, Blake KV, Cabana MD, Castro M, Chmiel JF, Covar R, Fitzpatrick A, Gaffin JM, Gentile D, Israel E, Jackson DJ, Kraft M, Krishnan JA, Kumar HV, Lang JE, Lazarus SC, Lemanske RF, Lima J, Martinez FD, Morgan W, Moy J, Myers R, Naureckas ET, Ortega VE, Peters SP, Phipatanakul W, Pongracic JA, Ross K, Sheehan WJ, Smith LJ, Solway J, Sorkness CA, Wechsler ME, Wenzel S, White SR, Holguin F. Geography, generalisability, and susceptibility in clinical trials. Lancet Respir Med. 2021 04; 9(4):330-332.  View on PubMed
  9. Wang K, Verbakel JY, Oke J, Fleming-Nouri A, Harada N, Atsuta R, Fujisawa T, Kawayama T, Inoue H, Lazarus S, Szefler S, Martinez FD, Shaw D, Pavord ID, Thomas M. Using fractional exhaled nitric oxide to guide step-down treatment decisions in asthma: practical considerations. Eur Respir J. 2020 08; 56(2).  View on PubMed
  10. Cooper CB, Paine R, Curtis JL, Kanner RE, Martinez CH, Meldrum CA, Bowler R, O'Neal W, Hoffman EA, Couper D, Quibrera M, Criner G, Dransfield MT, Han MK, Hansel NN, Krishnan JA, Lazarus SC, Peters SP, Barr RG, Martinez FJ, Woodruff PG, SPIROMICS investigators. Novel Respiratory Disability Score Predicts COPD Exacerbations and Mortality in the SPIROMICS Cohort. Int J Chron Obstruct Pulmon Dis. 2020; 15:1887-1898.  View on PubMed
  11. Panettieri RA, Kolls JK, Lazarus S, Corder S, Harshman A, Langmack E, Petrache I. Impact of a Respiratory Disease Young Investigators' Forum on the Career Development of Physician-Scientists. ATS Sch. 2020 Jun 16; 1(3):243-259.  View on PubMed
  12. Wang K, Verbakel JY, Oke J, Fleming-Nouri A, Brewin J, Roberts N, Harada N, Atsuta R, Takahashi K, Mori K, Fujisawa T, Shirai T, Kawayama T, Inoue H, Lazarus S, Szefler S, Martinez F, Shaw D, Pavord ID, Thomas M. Using fractional exhaled nitric oxide to guide step-down treatment decisions in patients with asthma: a systematic review and individual patient data meta-analysis. Eur Respir J. 2020 05; 55(5).  View on PubMed
  13. Leitao Filho FS, Mattman A, Schellenberg R, Criner GJ, Woodruff P, Lazarus SC, Albert RK, Connett J, Han MK, Gay SE, Martinez FJ, Fuhlbrigge AL, Stoller JK, MacIntyre NR, Casaburi R, Diaz P, Panos RJ, Cooper JA, Bailey WC, LaFon DC, Sciurba FC, Kanner RE, Yusen RD, Au DH, Pike KC, Fan VS, Leung JM, Man SP, Aaron SD, Reed RM, Sin DD. Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis. Chest. 2020 10; 158(4):1420-1430.  View on PubMed
  14. Woodruff PG, Lazarus SC. Long-term Sequelae of Nonobstructive Chronic Bronchitis-Is Airflow Obstruction Important? JAMA Intern Med. 2020 05 01; 180(5):686-687.  View on PubMed
  15. Jerry Krishnan, Stephen Lazarus, Kathryn Blake, Ronina Covar, Anne-Marie Dyer, Christine Sorkness, Sally Wenzel, Jason Lang, Njira Lugogo, David Mauger, Tonya King on behalf of AsthmaNet investigators. Predicting response to inhaled corticosteroid or long-acting muscarinic antagonist in mild persistent asthma. Journal of Allergy and Clinical Immunology. 2020 Feb 1; 145(2):ab338.  View on PubMed
  16. Dransfield MT, Voelker H, Bhatt SP, Brenner K, Casaburi R, Come CE, Cooper JAD, Criner GJ, Curtis JL, Han MK, Hatipoglu U, Helgeson ES, Jain VV, Kalhan R, Kaminsky D, Kaner R, Kunisaki KM, Lambert AA, Lammi MR, Lindberg S, Make BJ, Martinez FJ, McEvoy C, Panos RJ, Reed RM, Scanlon PD, Sciurba FC, Smith A, Sriram PS, Stringer WW, Weingarten JA, Wells JM, Westfall E, Lazarus SC, Connett JE, BLOCK COPD Trial Group. Metoprolol for the Prevention of Acute Exacerbations of COPD. N Engl J Med. 2019 12 12; 381(24):2304-2314.  View on PubMed
  17. Wechsler ME, Szefler SJ, Ortega VE, Pongracic JA, Chinchilli V, Lima JJ, Krishnan JA, Kunselman SJ, Mauger D, Bleecker ER, Bacharier LB, Beigelman A, Benson M, Blake KV, Cabana MD, Cardet JC, Castro M, Chmiel JF, Covar R, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Grossman N, Holguin F, Jackson DJ, Kumar H, Kraft M, LaForce CF, Lang J, Lazarus SC, Lemanske RF, Long D, Lugogo N, Martinez F, Meyers DA, Moore WC, Moy J, Naureckas E, Olin JT, Peters SP, Phipatanakul W, Que L, Raissy H, Robison RG, Ross K, Sheehan W, Smith LJ, Solway J, Sorkness CA, Sullivan-Vedder L, Wenzel S, White S, Israel E, NHLBI AsthmaNet. Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma. N Engl J Med. 2019 09 26; 381(13):1227-1239.  View on PubMed
  18. Grossman NL, Ortega VE, King TS, Bleecker ER, Ampleford EA, Bacharier LB, Cabana MD, Cardet JC, Carr TF, Castro M, Denlinger LC, Denson JL, Fandino N, Fitzpatrick AM, Hawkins GA, Holguin F, Krishnan JA, Lazarus SC, Nyenhuis SM, Phipatanakul W, Ramratnam SK, Wenzel S, Peters SP, Meyers DA, Wechsler ME, Israel E. Exacerbation-prone asthma in the context of race and ancestry in Asthma Clinical Research Network trials. J Allergy Clin Immunol. 2019 12; 144(6):1524-1533.  View on PubMed
  19. Cardet JC, Jiang X, Lu Q, Gerard N, McIntire K, Boushey HA, Castro M, Chinchilli VM, Codispoti CD, Dyer AM, Holguin F, Kraft M, Lazarus S, Lemanske RF, Lugogo N, Mauger D, Moore WC, Moy J, Ortega VE, Peters SP, Smith LJ, Solway J, Sorkness CA, Sumino K, Wechsler ME, Wenzel S, Israel E, AsthmaNet Investigators. Reply. J Allergy Clin Immunol. 2019 09; 144(3):873-874.  View on PubMed
  20. Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R, Lugogo N, Wenzel S, Chinchilli VM, Mauger DT, Dyer AM, Boushey HA, Fahy JV, Woodruff PG, Bacharier LB, Cabana MD, Cardet JC, Castro M, Chmiel J, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Hastie A, Holguin F, Israel E, Jackson D, Kraft M, LaForce C, Lemanske RF, Martinez FD, Moore W, Morgan WJ, Moy JN, Myers R, Peters SP, Phipatanakul W, Pongracic JA, Que L, Ross K, Smith L, Szefler SJ, Wechsler ME, Sorkness CA, National Heart, Lung, and Blood Institute AsthmaNet. Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level. N Engl J Med. 2019 05 23; 380(21):2009-2019.  View on PubMed

Go to UCSF Profiles, powered by CTSI