David A. Hafler

Research Statement

AI generated · 14h ago

David A. Hafler's indexed work centers on regulatory T cell biology and its failure in autoimmunity, anchored by studies of FOXP3+ regulatory T cells in the human immune system and the loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. Earlier work identified CD4+CD25high regulatory cells in human peripheral blood, helping establish a suppressive population later linked to disease. A parallel line examines sodium chloride-driven induction of pathogenic TH17 cells, alongside IL-21 and TGF-β requirements for human TH17 differentiation, implicating environmental and cytokine signals in autoimmune pathogenesis. Beyond these, Hafler contributed to large genetic efforts, including mapping causal autoimmune disease variants through genetic and epigenetic fine mapping and a genome-wide analysis identifying 48 new susceptibility variants for multiple sclerosis. He also helped characterize TIGIT-expressing Treg cells that selectively inhibit proinflammatory Th1 and Th17 responses. No software, datasets, patents, or grants are indexed beyond publications. Across these works, the throughline is a shift from identifying regulatory and effector T cell subsets toward defining the genetic and environmental mechanisms that tip immune balance toward autoimmunity.

Most Cited Works

Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain

Samuel E Marsh, Alec J Walker, Tushar Kamath, Lasse Dissing-Olesen, Timothy R Hammond, T Yvanka de Soysa, Adam M H Young, Sarah Murphy, Abdulraouf Abdulraouf, Naeem Nadaf, Connor Dufort, Alicia C Walker, Liliana E Lucca, Velina Kozareva, Charles Vanderburg, Soyon Hong, Harry Bulstrode, Peter J Hutchinson, Daniel J Gaffney, David A Hafler, Robin J M Franklin, Evan Z Macosko, Beth Stevens

Nature Neuroscience2022

432Citations

Research Areas

T-cell and B-cell ImmunologyMultiple Sclerosis Research StudiesPsoriasis: Treatment and PathogenesisGenetic Associations and EpidemiologyImmunotherapy and Immune Responses

Affiliations & Education

Employment

2006–2026
Yale University(US)
Professor · Immunobiology and Neurology

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Sources

Research Statement

Most Cited Works

Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain

Research Areas

Affiliations & Education

Employment

High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq

The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases

NEBULA is a fast negative binomial mixed model for differential or co-expression analysis of large-scale multi-subject single-cell data

Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19