David Erle, MD

Director, UCSF Functional Genomics Core Facility
Professor
Department of Medicine
+1 415 514-4370
Research Description: 

Dr. Erle received an A.B. degree (Biochemistry) from Harvard College in 1980 and an M.D. degree from UCSF in 1984. He was trained in internal medicine and in pulmonary disease at UCSF. As a CVRI research fellow training at the UCSF Lung Biology Center, he studied leukocyte integrins with Robert Pytela and Dean Sheppard. He joined the Lung Biology Center faculty in 1990. His academic activities include laboratory research and clinical teaching. He founded the UCSF Functional Genomics Core Facility. He is a member of the Bakar ImmunoX Program, the Cardiovascular Research Institute, and the Institute for Human Genetics.

Research Interests:

Asthma affects ~300 million people and causes ~250,000 deaths annually. The long-term overall vision of our research program is that fundamental insights into the biology of the airway epithelium will allow us to better understand asthma and other airway diseases and provide a firm foundation for developing new approaches to prevention, cure, or treatment of these diseases.

The concept that the airway epithelium plays a central role in asthma pathogenesis represents a relatively recent paradigm shift. We showed that direct effects of the type 2 cytokine IL-13 on resident airway cells were sufficient to induce airway hyperreactivity (AHR) and mucus overproduction. Our most important early contribution was the demonstration that IL-13-driven activation of the transcription factor (TF) STAT6 in airway epithelial cells causes AHR and mucus overproduction in mice. More recently, our studies of primary human bronchial epithelial (HBE) cells showed that IL-13 induces changes in expression, organization, and function of airway mucus glycoproteins (MUC5AC and MUC5B mucins). These changes lead to attachment (tethering) of mucus to the epithelium, prevent normal mucus clearance, and promote formation of obstructive mucus plugs that are a prominent feature of fatal asthma.

Completed and ongoing studies in the lab are intended to help reach a deeper understanding of the molecular mechanisms underlying airway epithelial dysfunction in asthma. We study the mechanisms of gene regulation in the airway epithelium and determine the contributions of specific gene expression changes to changes in airway epithelial function. We use a variety of approaches from cell and molecular biology, genomics, and computational biology. We have adapted powerful new methods, including single cell RNA-seq (scRNA-seq), ChIP-seq, and CRISPR, for use with HBE cells as well as with cells obtained directly from individuals with asthma. We collaborate extensively with experts in asthma clinical studies, genetics and genomics, and computational biology.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Human Genetics
Research Summary: 
Immunopathogenesis of Asthma; Genomics of Disease

Websites

Featured Publications: 

Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma.

The Journal of clinical investigation

Bonser LR, Zlock L, Finkbeiner W, Erle DJ

Massively parallel functional annotation of 3' untranslated regions.

Nature biotechnology

Zhao W, Pollack JL, Blagev DP, Zaitlen N, McManus MT, Erle DJ

Airway epithelial miRNA expression is altered in asthma.

American journal of respiratory and critical care medicine

Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR, Hou L, Nguyen C, Solon M, Nguyen C, Barczak AJ, Zlock LT, Blagev DP, Finkbeiner WE, Ansel KM, Arron JR, Erle DJ, Woodruff PG

Distinct roles of FOXA2 and FOXA3 in allergic airway disease and asthma.

American journal of respiratory and critical care medicine

Park SW, Verhaeghe C, Nguyenvu LT, Barbeau R, Eisley CJ, Nakagami Y, Huang X, Woodruff PG, Fahy JV, Erle DJ

The protein disulfide isomerase AGR2 is essential for production of intestinal mucus.

Proceedings of the National Academy of Sciences of the United States of America

Park SW, Zhen G, Verhaeghe C, Nakagami Y, Nguyenvu LT, Barczak AJ, Killeen N, Erle DJ

Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma.

Nature medicine

Kuperman DA, Huang X, Koth LL, Chang GH, Dolganov GM, Zhu Z, Elias JA, Sheppard D, Erle DJ