John Fahy, MD

Professor
Department of Medicine
+1 415 476-9940
Research Description: 

I am a Professor of Medicine in the Division of Pulmonary and Critical Care Medicine and the Department of Medicine at UCSF. I direct a research program in asthma and other airway diseases that is human centered and focused on uncovering disease mechanisms and improving treatment.

MAJOR GOALS: (i) To define abnormalities in airway epithelial cell function that contribute to abnormal type 2 immune responses in asthma; (ii) To explore mechanisms of formation of pathologic mucus gels in the airway so that novel mucolytics can be developed; (iii) To explore the heterogeneity of molecular mechanisms in asthma to improve prospects for treatment approaches that are patient specific.

(i) ABNORMAL TYPE 2 IMMUNE RESPONSES IN HUMAN ASTHMA: The airway epithelium has emerged as an important regulator of innate and adaptive immune responses that result in type 2 allergic airway inflammation. My lab is specifically investigating epithelial mechanisms that contribute to upregulation of Th2 cytokines in the asthmatic airway. Our experimental approaches include gene and protein expression analysis of airway epithelial brushings, biopsies, and secretions, and cell culture studies in airway epithelial cells from human donors. We collaborate with multiple other UCSF labs, including the Locksley, Ansel, and Woodruff labs.

(ii) PATHOLOGIC MUCUS GELS: The formation of pathologic mucus is a feature of multiple lung diseases and has multiple consequences for lung health, including airflow obstruction and infections. My lab is investigating how pathologic mucus gels form. Our experimental approaches include detailed analyses of sputum samples using rheology-, imaging- and biochemistry-based approaches. We use the data from analysis of pathologic mucus to inform strategies for development of novel mucolytics. Important collaborators include Drs Stefan Oscarson and Stephen Carrington at University College Dublin.

(iii) HETEROGENEITY OF MOLECULAR MECHANISMS IN ASTHMA: Many asthmatics do not respond well to currently available treatments and one reason is that current medications assume a one size fits all approach. My lab is applying a variety of targeted and unbiased approaches to investigate disease mechanism in large numbers of asthmatics with a view to improving understanding of the range and frequency of disease mechanisms that underlie asthma. Our experimental approaches include detailed analysis of the differential expression of genes and proteins in airway biospecimens collected from highly characterized patients with asthma and healthy controls. We also simultaneously explore how simpler tests in blood might reveal specific disease mechanisms and serve as biomarkers for personalizing treatment. Our work in this area is done in collaboration with the Woodruff lab at UCSF and with investigators in the NIH Severe Asthma Research Program (SARP).

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Research Summary: 
Mechanism Oriented Clinical Research in Airway Disease

Websites

Publications: 

Evidence for Exacerbation-Prone Asthma and Predictive Biomarkers of Exacerbation Frequency.

American journal of respiratory and critical care medicine

Peters MC, Mauger D, Ross KR, Phillips B, Gaston B, Cardet JC, Israel E, Levy BD, Phipatanakul W, Jarjour NN, Castro M, Wenzel SE, Hastie A, Moore W, Bleecker E, Fahy JV, Denlinger LC

The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations.

Journal of biopharmaceutical statistics

Ivanova A, Israel E, LaVange LM, Peters MC, Denlinger LC, Moore WC, Bacharier LB, Marquis MA, Gotman NM, Kosorok MR, Tomlinson C, Mauger DT, Georas SN, Wright RJ, Noel P, Rosner GL, Akuthota P, Billheimer D, Bleecker ER, Cardet JC, Castro M, DiMango EA, Erzurum SC, Fahy JV, Fajt ML, Gaston BM, Holguin F, Jain S, Kenyon NJ, Krishnan JA, Kraft M, Kumar R, Liu MC, Ly NP, Moy JN, Phipatanakul W, Ross K, Smith LJ, Szefler SJ, Teague WG, Wechsler ME, Wenzel SE, White SR

Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways.

The Journal of allergy and clinical immunology

Li X, Christenson SA, Modena B, Li H, Busse WW, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston B, Hastie AT, Israel E, Jarjour NN, Levy BD, Moore WC, Woodruff PG, Kaminski N, Wenzel SE, Bleecker ER, Meyers DA

Reply to Nannini and Lipworth et al.

American journal of respiratory and critical care medicine

Peters MC, Fahy JV, Denlinger LC

COVID-19 Related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids.

American journal of respiratory and critical care medicine

Peters MC, Sajuthi S, Deford P, Christenson S, Rios CL, Montgomery MT, Woodruff PG, Mauger DT, Erzurum SC, Johansson MW, Denlinger LC, Jarjour NN, Castro M, Hastie AT, Moore W, Ortega VE, Bleecker ER, Wenzel SE, Israel E, Levy BD, Seibold MA, Fahy JV