The broad, long term objective of the Stanford Technology Accelerating Medicines Partnership (STAMP) Center is to serve as the leader within the RA/SLE AMP Network in the development and implementation of multiplexed mechanistic assays for AMP studies. Although we propose to focus on SLE, our methods will be used in pilot studies for RA and can be applied to any autoimmune disease. Investigators participating in this AMP proposal, and other collaborators at Stanford, have been leading innovators in the development of high-throughput genomics and proteomics technologies for studying cancer and autoimmunity. Project 1 (Steve Quake and Howard Chang) will perform transcript profiling using RNA-Seq of single cells isolated from tissue samples and blood, then separating into individual wells using Fluidigm-based microfluidics devices (C1) or FACS. The Chang lab will determine binding of transcription factors to open chromatin, repressing and/or activating transcriptional programs involving NFAT, NFB, RORs, IRFs, STATs, and other transcription factors. Project 2 (Garry Nolan) will employ CyTOF to study cells obtained from blood and tissue, characterizing cell surface molecules, signaling molecules, and phospho-specific epitopes in discrete cellular subsets. Upregulated transcripts from Project 1 will inform selection of CyTOF antibodies in an iterative process during the UH3 funding period. Project 3 (Bill Robinson, Mark Davis and PJ Utz) will use autoantibody profiling, FACS, repertoire-sequencing and yeast display to characterize antigen- specific B and T cells in blood and isolated from tissues. The Robinson and Davis labs will characterize the B and T cell receptor repertoire by sequencing heavy and light chain genes from FACS sorted plasmablasts, and FACS or tetramer sorted T cells, as well as cells isolated from tissue. Monoclonal antibodies will be cloned, expressed, and purified for antigen identification. Antigen targets will be discovered (Utz and Robinson) using protein arrays, which will serve as a core assay for all AMP Network Centers. Pilot projects are also proposed including plasma virome sequencing and two projects to develop and implement multiplexed ion beam imaging (MIBI). Finally, to insure availability of blood, kidney, skin, and synovium for our studies, subjects will be recruited from Stanford and the Bay Area (SLE); UCLA and Cedars- Sinai (SLE); and UCSD (RA), as well as from other AMP Centers. Integration of all assays at one AMP Center will facilitate discovery of pathways, molecules, and new drug targets.

Public Health Relevance

STAMP is a Technology Research Center that will focus on systemic lupus erythematosus and rheumatoid arthritis. STAMP will employ novel technologies to determine, at the single cell level, genes, proteins, and pathways that are abnormal and may serve as drug targets.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Exploratory/Developmental Cooperative Agreement Phase I (UH2)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Serrate-Sztein, Susana
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Good, Zinaida; Sarno, Jolanda; Jager, Astraea et al. (2018) Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse. Nat Med 24:474-483
Goltsev, Yury; Samusik, Nikolay; Kennedy-Darling, Julia et al. (2018) Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging. Cell 174:968-981.e15
Elliott, Serra E; Kongpachith, Sarah; Lingampalli, Nithya et al. (2018) Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis. Arthritis Rheumatol 70:1946-1958
Burns, Tyler J; Frei, Andreas P; Gherardini, Pier F et al. (2017) High-throughput precision measurement of subcellular localization in single cells. Cytometry A 91:180-189
Haddon, D James; Wand, Hannah E; Jarrell, Justin A et al. (2017) Proteomic Analysis of Sera from Individuals with Diffuse Cutaneous Systemic Sclerosis Reveals a Multianalyte Signature Associated with Clinical Improvement during Imatinib Mesylate Treatment. J Rheumatol 44:631-638
Der, Evan; Ranabothu, Saritha; Suryawanshi, Hemant et al. (2017) Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis. JCI Insight 2:
Jensen, Helle; Chen, Shih-Yu; Folkersen, Lasse et al. (2017) EBI3 regulates the NK cell response to mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 114:1625-1630
Mukherjee, Sayak; Jensen, Helle; Stewart, William et al. (2017) In silico modeling identifies CD45 as a regulator of IL-2 synergy in the NKG2D-mediated activation of immature human NK cells. Sci Signal 10:
Dodd, Dylan; Spitzer, Matthew H; Van Treuren, William et al. (2017) A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 551:648-652
Wernig, Gerlinde; Chen, Shih-Yu; Cui, Lu et al. (2017) Unifying mechanism for different fibrotic diseases. Proc Natl Acad Sci U S A 114:4757-4762

Showing the most recent 10 out of 18 publications