Wells Laboratory

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The Wells Laboratory studies the cell-intrinsic mechanisms that the immune system uses to decode extracellular signals and translate these into the appropriate immune vs. tolerant responses. The lab has defined a series of intracellular proteins that sense signals from costimulatory and growth factor receptors and translate them into transcriptional responses.

In particular, the Wells Lab studies how transcription factors establish immunoregulatory gene expression programs in T cells through cooperation with chromatin remodeling and DNA methylation complexes. The lab team has two decades of experience in cellular immunology, cell biology, and molecular biology research, including mouse models, in vivo and in vitro human and mouse lymphocyte function, biochemistry, transcriptional biology and epigenetics.

As part of its research, the lab has incorporated approaches such as ChIP-seq, ATAC-seq, 4C-seq and Capture-C to study genome-wide transcription factor occupancy, histone modification, and long-range interactions between enhancers and promoters. These approaches take advantage of deep sequencing resources and the bioinformatic expertise needed to analyze the genome-scale data sets at The Center for Spatial and Functional Genomics, which lab director Andrew Wells, PhD co-directs.

Project Highlights

  • Regulation of Immune Tolerance by Cyclin-Dependent Kinases
    • The CDK2-p27kip1 axis regulates transplant tolerance
    • CDK2 regulates IL-2 production by Tconv
    • CDK2 phosphorylates and targets FOXP3 for degradation
  • Transcriptional and Epigenetic Regulation of T cell Function
    • Reprogramming of T cell function by FOXP3
    • Silencing of effector programs by IKAROS
    • Imprinting T cell fate choices by de novo DNA Methylation (DNMT3A)
    • Mapping 3D Gene CIS-regulatory architectures (IL2, IL17)
    • Understanding how genetic polymorphisms contribute to disease risk by genome-scale mapping of promoter-enhanced interactomes
Leader

Andrew D. Wells, PhD

Co-Director, Spatial and Functional Genomics Research Affinity Group
Dr. Wells studies the genetic, epigenetic, and transcriptional mechanisms that control T lymphocyte immunity and tolerance.