The Altin Lab

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The Altin Lab

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    • John Altin, PhD
    • Sophia Carvalho, PhD
    • Heather Mead, PhD
    • Jorge Soria-Bustos, PhD
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    • Caroline Harms, MS
    • Sierra Henson, BS
    • Georgia Nelson, BS
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  • More
    • Home
    • MyImmunity
    • Personnel
      • John Altin, PhD
      • Sophia Carvalho, PhD
      • Heather Mead, PhD
      • Jorge Soria-Bustos, PhD
      • Erin Kelley, MS
      • Caroline Harms, MS
      • Sierra Henson, BS
      • Georgia Nelson, BS
    • Projects
      • Tuberculosis
      • Single B Cell Analysis
      • Cancer
      • Transplantation
    • News
    • Job Postings
      • Part-time: Intern
    • Technology
      • MHC-PepSeq
      • Single-Cell Genomics
    • Our Partners

  • Home
  • MyImmunity
  • Personnel
    • John Altin, PhD
    • Sophia Carvalho, PhD
    • Heather Mead, PhD
    • Jorge Soria-Bustos, PhD
    • Erin Kelley, MS
    • Caroline Harms, MS
    • Sierra Henson, BS
    • Georgia Nelson, BS
  • Projects
    • Tuberculosis
    • Single B Cell Analysis
    • Cancer
    • Transplantation
  • News
  • Job Postings
    • Part-time: Intern
  • Technology
    • MHC-PepSeq
    • Single-Cell Genomics
  • Our Partners

Tuberculosis

Systems analyses of the interaction between T cells and TB

  

Tuberculosis (TB) is a leading global infectious killer responsible for > 1 million deaths per year, the majority of which occur in resource-constrained settings. While an effective TB vaccine is therefore an urgent global health priority, progress has been disappointing, with the last major landmark being the development of BCG a century ago. Recently, the tools of genomics have offered new, systems-level views of anti-TB immunity that have the potential to illuminate more rational approaches to vaccine development.

To that end, we are working to generate systems-level analyses of the CD4 T cell response to TB in 2-dimensions:


(i) The first dimension is the TB genome, where we will combine TGen’s expertise in pathogen genomics with novel, multiplexed technologies to survey T cell antigenicity across the pathogen’s ~4000 genes. Phylogenetic evidence already provides clues that T cell reactivity to different regions of the TB genome may have differential effects, and we expect this genome-wide analysis to provide new insights into host-pathogen adaptation and highlight TB genes that may be priority targets for protective immunity.


(ii) The second dimension is the human genome. Using high-dimensional probesets developed in the TB genome-wide analysis, we plan to apply single cell methods to study the transcriptional landscape of TB-specific T cells in different disease settings. A simultaneous view of T cell states and specificities has the potential to define new T cell correlates of disease and protection.


Time for a New Tactic

Simultaneous analysis of T cell

specificity & phenotype. (a) Conceptual diagram of the diversity of T cell specificities against Mtb (x-axis) vs. phenotypes /functions (y-axis). (b) Map of T cell technologies (existing vs. proposed) for T cell evaluation & their capacity for simultaneous evaluation of many antigen specificities (x-axis) and phenotypes (y-axis).

Working on This:

Caroline Harms

Caroline Harms

Caroline Harms

Research Associate

Heather Mead

Caroline Harms

Caroline Harms

Project Manager

Sierra Henson

Caroline Harms

Sierra Henson

Research Associate

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