Our laboratory is dedicated to unraveling the intricate crosstalk between epigenetic and transcriptional mechanisms that shape T lymphocyte biology. We are interested in 3 main areas

Cell fate 

Cell fate decision-making is a frequent event that most T cells in our body encounter. Developmentally, abT cells, which comprise the majority of T cells in our body, commit to becoming CD4⁺ helper or CD8⁺ cytotoxic T cells from a common bipotent precursor. Critical signals received at the time of commitment influence these cell fate outcomes. Importantly, signals received during the commitment process also impart vital epigenetic features that maintain their identity in the periphery in a heritable manner. These signals also affect the heterogeneous cellular states/fates they adopt in the periphery. We are interested in understanding the signals that govern T cell commitment, the intrinsic epigenetic mechanisms that confer heritable signatures that guide their peripheral cell fates.

Development of T lymphocytes with tolerogenic properties 

We investigate the molecular pathways that drive the development of T cells with tolerogenic properties. These cells, which include Regulatory CD4 T cells, are essential for homeostasis and for the prevention of overt immune responses to self and innocuous antigens such as food. Our goal is to understand how these gene programs are established and regulated, and how they can be harnessed or reprogrammed for clinical therapies.

Modulation of T cell fitness in disease contexts

 We explore how epigenetic and transcriptional networks influence T cell performance and resilience in autoimmune disorders, cancer, and infectious diseases, aiming to identify new targets for improving immune function and patient outcomes.

Inactive Rhomboids and ADAMs (Joint focus with Maretzky Lab)

As a joint collaboration with the Maretzky Lab, we pursue studies looking at the role of an intriguing group of inactive proteases known as the inactive rhomboids, iRhoms, and their modulation of innate and adaptive immune responses in mice. iRhoms are catalytically dead homologues of their active counterparts, the rhomboid proteases: a group of intramembrane serine proteases that mediates the proteolytic cleavage of membrane‐tethered ligands in Drosophila. However, the conserved function of rhomboids in flies seems to have diverged in mammals whereby they have lost their catalytic function but remarkably, iRhoms are evolutionarily conserved and present in all metazoans and control key signaling pathways such as EGFR signaling and TNF signaling. The two mammalian homologs, iRhom1 and iRhom2 exhibit tissue‐restricted expression and the joint focus of the Maretzky/Issuree labs is a) to understand the molecular aspects controlling tissue-specific expression and function of iRhoms and b) to evaluate the respective roles of iRhom1 and 2 in modulating inflammation and immunity using mouse models.

Visit Dr. Maretzky's lab: https://maretzky.lab.uiowa.edu