The Poholek Lab
Our lab is interested in exploring how tissue-specific environmental factors alter transcriptomes and epigenomes of T cells that control their differentiation in the context of diseases such as Th2 differentiation in allergic asthma and T cell exhaustion in the tumor.
Ongoing Research Projects
Tissue specific functions of Blimp-1
Transcription factors play a critical role in modulating the transcriptome and epigenome of cells. Blimp-1 is a BTB/POZ zinc finger transcription factor expressed by many cell types, including T and B cells. In T cells, we have identified context-dependent functions of Blimp-1 controlling T cell differentiation and effector function and are exploring the molecular regulation and function of Blimp-1 as a model transcription factor that controls immune cells in health in disease. Our research on Blimp-1 seeks to answer the following questions:
How is Blimp-1 regulated in a cell-type specific manner?
What is the molecular function of Blimp-1 in vivo in various immunological contexts?
Our studies have uncovered novel genomic elements controlling the expression of Blimp-1 and the tissue-specific functions of Blimp-1 that control autoimmunity while also promoting responses to allergens. Using genetic mouse models and NextGen sequencing technologies, we are, at the molecular level, exploring how this important transcription factor shapes T cell differentiation and function at homeostasis and in the face of contextual environmental changes.
Epigenetic landscape of T cell exhaustion in the tumor
In collaboration with Greg Delgoffe, PhD, at the UPMC Hillman Cancer Center, we are exploring the epigenetics of T cells in murine tumors using a new low-cell number ChIP-seq assay (CUT & RUN) developed by Steven Henikoff, PhD, at the Fred Hutchinson Cancer Research Center. As T cells enter a tumor’s micro-environment, they experience a unique combination of signals that promote a state of T cell dysfunction (also called exhaustion). Our lab is working to understand the transcriptomic and epigenomic landscape of T cell exhaustion in a tumor in order to understand the signals that drive exhaustion and identify novel therapeutic targets for immunotherapy.
We are currently investigating alterations in 3D chromatin conformation using Hi-C and CUT&Tag to investigate how changes in 3D chromatin structure may drive T cell dysfunction in the tumor.
Spatial Transcriptomics and T cell context dependent function
We are interested in leveraging novel technologies to understand T cell functions in a variety of contexts. One way to to study T cell function is with spatial transcriptomics to identify the tissue resident identity of T cells and how they interact with other cells within tissues.