John Fahy, MD

Professor
Department of Medicine
+1 415 476-9940

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: 

After asthma: redefining airways diseases.

Lancet (London, England)

Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, Cullinan P, Custovic A, Ducharme FM, Fahy JV, Frey U, Gibson P, Heaney LG, Holt PG, Humbert M, Lloyd CM, Marks G, Martinez FD, Sly PD, von Mutius E, Wenzel S, Zar HJ, Bush A

Baseline Features of the Severe Asthma Research Program (SARP III) Cohort: Differences with Age.

The journal of allergy and clinical immunology. In practice

Teague WG, Phillips BR, Fahy JV, Wenzel SE, Fitzpatrick AM, Moore WC, Hastie AT, Bleecker ER, Meyers DA, Peters SP, Castro M, Coverstone AM, Bacharier LB, Ly NP, Peters MC, Denlinger LC, Ramratnam S, Sorkness RL, Gaston BM, Erzurum SC, Comhair SAA, Myers RE, Zein J, DeBoer MD, Irani AM, Israel E, Levy B, Cardet JC, Phipatanakul W, Gaffin JM, Holguin F, Fajt ML, Aujla SJ, Mauger DT, Jarjour NN

Corticosteroid and Long-Acting ß-Agonist Therapy Reduces Epithelial Goblet Cell Metaplasia.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

Lachowicz-Scroggins ME, Finkbeiner WE, Gordon ED, Yuan S, Zlock L, Bhakta NR, Woodruff PG, Fahy JV, Boushey HA

ALX receptor ligands define a biochemical endotype for severe asthma.

JCI insight

Ricklefs I, Barkas I, Duvall MG, Cernadas M, Grossman NL, Israel E, Bleecker ER, Castro M, Erzurum SC, Fahy JV, Gaston BM, Denlinger LC, Mauger DT, Wenzel SE, Comhair SA, Coverstone AM, Fajt ML, Hastie AT, Johansson MW, Peters MC, Phillips BR, Levy BD

Asthma and corticosteroids: time for a more precise approach to treatment.

The European respiratory journal

Dunican EM, Fahy JV