Honors & Awards


  • Irene Diamond/AFAR Postdoctoral Transition Award, American Federation of Aging Research (2019)
  • Junior Faculty Award, AD/PD 2019 Congress (2019)
  • Ruth L. Kirchstein NRSA Postdoctoral Fellowship, NIH/NIA (2018-2021)
  • Young Investigator Award, Alzheimer’s Association Bay Area (2018)
  • Postdoctoral Fellowship for Translational Research on Aging, Glenn/AFAR (2015)
  • Harold M. Weintraub Graduate Student Award Nominee, University of Southern California (2014)
  • Spring Scholar Award, University of Southern California (2014)
  • Young Investigator Award, Alzheimer’s Association Los Angeles (2014)
  • Zach Hall Award, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA (2014)
  • Ruth L. Kirchstein NRSA Pre-doctoral Fellowship, NIH/NINDS (2013-2015)
  • Excellence in Research Award, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA (2009)

Professional Education


  • Bachelor of Arts, University of California Santa Barbara (2007)
  • Doctor of Philosophy, University of Southern California (2015)

Stanford Advisors


All Publications


  • Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease. Nature Gate, D., Saligrama, N., Leventhal, O., Yang, A. C., Unger, M. S., Middeldorp, J., Chen, K., Lehallier, B., Channappa, D., De Los Santos, M. B., McBride, A., Pluvinage, J., Elahi, F., Tam, G. K., Kim, Y., Greicius, M., Wagner, A. D., Aigner, L., Galasko, D. R., Davis, M. M., Wyss-Coray, T. 2020

    Abstract

    Alzheimer's disease is an incurable neurodegenerative disorder in which neuroinflammation has a critical function1. However, little is known about the contribution of the adaptive immune response in Alzheimer's disease2. Here, using integrated analyses of multiple cohorts, we identify peripheral and central adaptive immune changes in Alzheimer's disease. First, we performed mass cytometry of peripheral blood mononuclear cells and discovered an immune signature of Alzheimer's disease that consists of increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. In a second cohort, we found that CD8+ TEMRA cells were negatively associated with cognition. Furthermore, single-cell RNA sequencing revealed that T cell receptor (TCR) signalling was enhanced in these cells. Notably, by using several strategies of single-cell TCR sequencing in a third cohort, we discovered clonally expanded CD8+ TEMRA cells in the cerebrospinal fluid of patients with Alzheimer's disease. Finally, we used machine learning, cloning and peptide screens to demonstrate the specificity of clonally expanded TCRs in the cerebrospinal fluid of patients with Alzheimer's disease to two separate Epstein-Barr virus antigens. These results reveal an adaptive immune response in the blood and cerebrospinal fluid in Alzheimer's disease and provide evidence of clonal, antigen-experienced T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration.

    View details for DOI 10.1038/s41586-019-1895-7

    View details for PubMedID 31915375

  • Undulating changes in human plasma proteome profiles across the lifespan. Nature medicine Lehallier, B., Gate, D., Schaum, N., Nanasi, T., Lee, S. E., Yousef, H., Moran Losada, P., Berdnik, D., Keller, A., Verghese, J., Sathyan, S., Franceschi, C., Milman, S., Barzilai, N., Wyss-Coray, T. 2019; 25 (12): 1843–50

    Abstract

    Aging is a predominant risk factor for several chronic diseases that limit healthspan1. Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues2-10, which supports a hypothesis that age-related molecular changes in blood could provide new insights into age-related disease biology. We measured 2,925 plasma proteins from 4,263 young adults to nonagenarians (18-95 years old) and developed a new bioinformatics approach that uncovered marked non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh and eighth decades of life reflected distinct biological pathways and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways that might offer potential targets for age-related diseases.

    View details for DOI 10.1038/s41591-019-0673-2

    View details for PubMedID 31806903

  • CD22 blockade restores homeostatic microglial phagocytosis in ageing brains NATURE Pluvinage, J. V., Haney, M. S., Smith, B. H., Sun, J., Iram, T., Bonanno, L., Li, L., Lee, D. P., Morgens, D. W., Yang, A. C., Shuken, S. R., Gate, D., Scott, M., Khatri, P., Luo, J., Bertozzi, C. R., Bassik, M. C., Wyss-Coray, T. 2019; 568 (7751): 187-+
  • CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Nature Pluvinage, J. V., Haney, M. S., Smith, B. A., Sun, J., Iram, T., Bonanno, L., Li, L., Lee, D. P., Morgens, D. W., Yang, A. C., Shuken, S. R., Gate, D., Scott, M., Khatri, P., Luo, J., Bertozzi, C. R., Bassik, M. C., Wyss-Coray, T. 2019

    Abstract

    Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, the mechanisms of impaired microglial homeostatic function and the cognitive effects of restoring this function remain unknown. We combined CRISPR-Cas9 knockout screens with RNAsequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. These screens identified CD22, a canonical Bcell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. CD22 mediates the anti-phagocytic effect of alpha2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-beta oligomers and alpha-synuclein fibrils in vivo. Long-term central nervous system delivery of an antibody that blocks CD22 function reprograms microglia towards a homeostatic transcriptional state and improves cognitive function in aged mice. These findings elucidate a mechanism of age-related microglial impairment and a strategy to restore homeostasis in the ageing brain.

    View details for PubMedID 30944478

  • Multiple Click-Selective tRNA Synthetases Expand Mammalian Cell-Specific Proteomics JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Yang, A. C., Du Bois, H., Olsson, N., Gate, D., Lehallier, B., Berdnik, D., Brewer, K. D., Bertozzi, C. R., Elias, J. E., Wyss-Coray, T. 2018; 140 (23): 7046–51

    Abstract

    Bioorthogonal tools enable cell-type-specific proteomics, a prerequisite to understanding biological processes in multicellular organisms. Here we report two engineered aminoacyl-tRNA synthetases for mammalian bioorthogonal labeling: a tyrosyl ( ScTyrY43G) and a phenylalanyl ( MmPheT413G) tRNA synthetase that incorporate azide-bearing noncanonical amino acids specifically into the nascent proteomes of host cells. Azide-labeled proteins are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization. Both mutant synthetases label human, hamster, and mouse cell line proteins and selectively activate their azido-bearing amino acids over 10-fold above the canonical. ScTyrY43G and MmPheT413G label overlapping but distinct proteomes in human cell lines, with broader proteome coverage upon their coexpression. In mice, ScTyrY43G and MmPheT413G label the melanoma tumor proteome and plasma secretome. This work furnishes new tools for mammalian residue-specific bioorthogonal chemistry, and enables more robust and comprehensive cell-type-specific proteomics in live mammals.

    View details for DOI 10.1021/jacs.8b03074

    View details for Web of Science ID 000435525500001

    View details for PubMedID 29775058