Person:
Goettel, Jeremy

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Goettel

First Name

Jeremy

Name

Goettel, Jeremy
Author's Publications: search.filters.isAuthorOfPublication.356b55a4-56c9-45bc-9937-7ac1c056de9f

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    WASP-mediated regulation of anti-inflammatory macrophages is IL-10 dependent and is critical for intestinal homeostasis
    (Nature Publishing Group UK, 2018) Biswas, Amlan; Shouval, Dror S.; Griffith, Alexandra; Goettel, Jeremy; Field, Michael; Kang, Yu Hui; Konnikova, Liza; Janssen, Erin; Redhu, Naresh; Thrasher, Adrian J.; Chatila, Talal; Kuchroo, Vijay; Geha, Raif; Notarangelo, Luigi D.; Pai, Sung-Yun; Horwitz, Bruce; Snapper, Scott
    Mutations in Wiskott–Aldrich syndrome protein (WASP) cause autoimmune sequelae including colitis. Yet, how WASP mediates mucosal homeostasis is not fully understood. Here we show that WASP-mediated regulation of anti-inflammatory macrophages is critical for mucosal homeostasis and immune tolerance. The generation and function of anti-inflammatory macrophages are defective in both human and mice in the absence of WASP. Expression of WASP specifically in macrophages, but not in dendritic cells, is critical for regulation of colitis development. Importantly, transfer of WT anti-inflammatory macrophages prevents the development of colitis. DOCK8-deficient macrophages phenocopy the altered macrophage properties associated with WASP deficiency. Mechanistically, we show that both WASP and DOCK8 regulates macrophage function by modulating IL-10-dependent STAT3 phosphorylation. Overall, our study indicates that anti-inflammatory macrophage function and mucosal immune tolerance require both WASP and DOCK8, and that IL-10 signalling modulates a WASP-DOCK8 complex.
  • Thumbnail Image
    Publication
    CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types
    (BioMed Central, 2016) Nelms, Bradlee D.; Waldron, Levi; Barrera, Luis A.; Weflen, Andrew W.; Goettel, Jeremy; Guo, Guoji; Montgomery, Robert K.; Neutra, Marian; Breault, David; Snapper, Scott; Orkin, Stuart; Bulyk, Martha; Huttenhower, Curtis; Lencer, Wayne
    We present a sensitive approach to predict genes expressed selectively in specific cell types, by searching publicly available expression data for genes with a similar expression profile to known cell-specific markers. Our method, CellMapper, strongly outperforms previous computational algorithms to predict cell type-specific expression, especially for rare and difficult-to-isolate cell types. Furthermore, CellMapper makes accurate predictions for human brain cell types that have never been isolated, and can be rapidly applied to diverse cell types from many tissues. We demonstrate a clinically relevant application to prioritize candidate genes in disease susceptibility loci identified by GWAS. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1062-5) contains supplementary material, which is available to authorized users.
  • Thumbnail Image
    Publication
    Haematopoietic stem and progenitor cells from human pluripotent stem cells
    (2018) Sugimura, Ryohichi; Jha, Deepak; Han, A Reum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted; Ditadi, Andrea; Keller, Gordon; Engelman, Alan; Snapper, Scott; Doulatov, Sergei; Daley, George
    A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.