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2018 Annual Report

2018 Annual Report

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Sandler Asthma Basic Research Center

Mission Statement

The Sandler Asthma Basic Research Center (SABRE Center) is an investigative unit dedicated to basic research discovery in asthma. Founded in 1999, the SABRE Center was nucleated by five basic scientists supported by advanced technology cores and linked with the larger scientific community through Center Grants and Program Projects focused around asthma research. With maturation, the Center aligned in 2014 with the Airway Clinical Research Center (ACRC) at UCSF to facilitate increased focus on and integration with studies in patients. Our mission remains to be a progressive, nimble, transformative scientific group that pioneers basic discovery in asthma research to accomplish our vision of a world free of asthma. The SABRE Center is made possible by the generous support of the Sandler Foundation.

Summary of Accomplishments over the Past Year

The SABRE Center continues to make innovative contributions to the understanding of asthma and allergic immunity and in establishing an active asthma research enterprise within the greater UCSF scientific community. Comprised of four basic scientists, a population geneticist and two translational scientists, the Center has networked across the greater UCSF research and the national asthma research organizations to establish increasing recognition for contributions to asthma research.

Notable accomplishments from SABRE Center members over the past 12 months:

  1. In the ACRC, Drs. Fahy and Woodruff described a new severe asthma endotype characterized by recurrent mucus plugging, poor drug control, and a high Th2-associated profile. These patients have a high incidence of recurrent nasal polyposis and were recognized by implementation of low-dose multidetector-CT radiography that allows the diagnosis and follow-up of this previously unrecognized asthma endotype (JCI 2018). Dr. Woodruff was part of an NIH study utilizing airway mucins as a marker for chronic bronchitis syndromes, some of which overlap with asthma phenotypes (NEJM 2017).
  2. In the genetics realm, where ancestry has marked effects on the course and treatment of asthma, the Burchard Asthma Collaboratory Data Bank contributed to elucidation of origins of native populations in Patagonia, the last part of the New World colonized by emigration out of Africa. Native Patagonians were identified as an anciently established Siberian descendent that divided into two primary clades, which were independently introgressed by subsequent waves of seafaring Southeast Asian and European populations (PNAS 2018). Such findings will assist in parsing out the complex genetics of allergy in highly admixed New World populations.
  3. In basic research, the Ansel lab established the microRNA landscape of ILC2s with the Locksley lab, opening up new interventional strategies (J Exp Med 2017); the Shin lab defined the role of MARCH ubiquitinylation of MHC molecules in protecting dendritic cells from proteotoxicity (J Cell Biol 2018); the Allen lab established efficient genetic engineering in human B cells using CRISPR/Cas9 (J Immunol Meth 2018); and the Locksley lab followed up their discovery of the role of epithelial tuft cells in type 2 immunity by defining the succinate receptor on tuft cells as a key luminal sensor that drives ILC2 activation in small intestine, a novel discovery (Cell 2018).

We look forward to ongoing successes in the coming year as we continue with our mission to conquer asthma.